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Summary Transfusion support is an essential element of modern emergency healthcare. Blood services together with hospital transfusion teams are required to prepare for, and respond to, mass casualty events as part of wider healthcare emergency planning. Preparedness is a constant collaborative process that actively identifies and manages potential risks, to prevent such events becoming a ‘disaster'. The aim of transfusion support during incidents is to provide sufficient and timely supply of blood components and diagnostic services, whilst maintaining support to other patients not involved in the event.

Background Preparatory, written plans for mass casualty incidents are designed to help hospitals deliver an effective response. However, addressing the frequently observed mismatch between planning and delivery of effective responses to mass casualty incidents is a key challenge. We aimed to use simulation-based iterative learning to bridge this gap. Methods We used Normalisation Process Theory as the framework for iterative learning from mass casualty incident simulations. Five small-scale ‘focused response' simulations generated learning points that were fed into two large-scale whole-hospital response simulations. Debrief notes were used to improve the written plans iteratively. Anonymised individual online staff surveys tracked learning. The primary outcome was system safety and latent errors identified from group debriefs. The secondary outcomes were the proportion of completed surveys, confirmation of reporting location, and respective roles for mass casualty incidents. Results Seven simulation exercises involving more than 700 staff and multidisciplinary responses were completed with debriefs. Usual emergency care was not affected by simulations. Each simulation identified latent errors and system safety issues, including overly complex processes, utilisation of space, and the need for clarifying roles. After the second whole hospital simulation, participants were more likely to return completed surveys (odds ratio=2.7; 95% confidence interval [CI], 1.7–4.3). Repeated exercises resulted in respondents being more likely to know where to report (odds ratio=4.3; 95% CI, 2.5–7.3) and their respective roles (odds ratio=3.7; 95% CI, 2.2–6.1) after a simulated mass casualty incident was declared. Conclusion Simulation exercises are a useful tool to improve mass casualty incident plans iteratively and continuously through hospital-wide engagement of staff.

Summary The emerging COVID‐19 pandemic has overwhelmed healthcare resources worldwide, and for transfusion services this could potentially result in rapid imbalance between supply and demand due to a severe shortage of blood donors. This may result in insufficient blood components to meet every patient's needs resulting in difficult decisions about which patients with major bleeding do and do not receive active transfusion support. This document, which was prepared on behalf of the National Blood Transfusion Committee in England, provides a framework and triage tool to guide the allocation of blood for patients with massive haemorrhage during severe blood shortage. Its goal is to provide blood transfusions in an ethical, fair, and transparent way to ensure that the greatest number of life years are saved. It is based on an evidence‐ and ethics‐based Canadian framework, and would become operational where demand for blood greatly exceeds supply, and where all measures to manage supply and demand have been exhausted. The guidance complements existing national shortage plans for red cells and platelets.

Objectives In 2015, three London cardiac centres, with different transfusion infrastructure support, merged to form the Barts Heart Centre. We describe the impact on transfusion rate, blood usage and interoperator variation. Design Data was collected on all adult patients undergoing cardiac surgery during 2014 as well as 2016, using the National Institute Cardiovascular Outcomes Research (NICOR) data set. Measurements and main results Over the two time periods, a total of 3,647 cardiac procedures were performed (1,930 in 2014 and 1,717 in 2016). There were no significant differences in type of surgery or patient comorbidity between the two epochs of time. Overall, red blood cell transfusion at 24 hours and until hospital discharge reduced significantly in 2016 (odds ratio 0.77; 95% confidence interval 0.68–0.89; p=0.0002). Interoperator variability (adjusted for comorbidities) reduced after merger from standard deviation 0.394 (standard error (SE) 0.096) to 0.269 (SE 0.082), p=0.001. Conclusion Clinical and organisational factors can improve transfusion service.

Objective The aim of this study was to identify the effects of recent innovations in trauma major hemorrhage management on outcome and transfusion practice, and to determine the contemporary timings and patterns of death. Background The last 10 years have seen a research-led change in hemorrhage management to damage control resuscitation (DCR), focused on the prevention and treatment of trauma-induced coagulopathy. Methods A 10-year retrospective analysis of prospectively collected data of trauma patients who activated the Major Trauma Centre's major hemorrhage protocol (MHP) and received at least 1 unit of red blood cell transfusions (RBC). Results A total of 1169 trauma patients activated the MHP and received at least 1 unit of RBC, with similar injury and admission physiology characteristics over the decade. Overall mortality declined from 45% in 2008 to 27% in 2017, whereas median RBC transfusion rates dropped from 12 to 4 units (massive transfusion rates from 68% to 24%). The proportion of deaths within 24 hours halved (33%-16%), principally with a fall in mortality between 3 and 24 hours (30%-6%). Survivors are now more likely to be discharged to their own home (57%-73%). Exsanguination is still the principal cause of early deaths, and the mortality associated with massive transfusion remains high (48%). Late deaths are now split between those due to traumatic brain injury (52%) and multiple organ dysfunction (45%). Conclusions There have been remarkable reductions in mortality after major trauma hemorrhage in recent years. Mortality rates continue to be high and there remain important opportunities for further improvements in these patients.

AprV2andaprB2are variants of the apr gene ofDichelobacter nodosus, the cause of footrot in sheep. They are putative markers for severe and mild disease expression. The aim of our study was to investigate the distribution ofaprV2andaprB2in flocks with and without footrot. Our hypotheses were that both strains are present in endemically affected flocks, withaprB2andaprV2associated with mild and virulent phenotypes respectively but thatD. nodosusis not present in flocks without footrot. Alternatively,aprB2persists in flocks without footrot. Despite extensive searching over 3 years only three flocks of sheep without footrot were identified.D. nodosuswas not detected in these three flocks. In one further flock, only mild interdigital dermatitis was observed, and onlyaprB2was detected. Twenty-four flocks with endemic footrot of all severities were sampled on three occasions and all were positive forD. nodosusand theaprV2variant;aprB2was detected in only 11 of these flocks.AprB2was detected as a co-infection withaprV2in the 22% of samples positive foraprB2and was more likely in mild footrot phenotypes than severe.Dichelobacter nodosusserogroups were not associated with footrot phenotype. We conclude thatD. nodosus, evenaprB2strains, do not persist in flocks in the absence of footrot. Our results support the hypothesis thataprB2is associated with mild footrot phenotypes. Finally, we conclude that given the small number of flocks without footrot that were identified, footrot is highly endemic in English sheep flocks.

Recent research demonstrates that transfusing whole blood (WB=red blood cells (RBC)+plasma+platelets) rather than just RBC (which is current National Health Service (NHS) practice) may improve outcomes for major trauma patients. As part of a programme to investigate provision of WB, NHS Blood and Transplant undertook a 2-year feasibility study to supply the Royal London Hospital (RLH) with (group O negative, ‘O neg’) leucodepleted red cell and plasma (LD-RCP) for transfusion of trauma patients with major haemorrhage in prehospital settings.Incidents requiring such prehospital transfusion occur randomly, with very high variation. Availability is critical, but O neg LD-RCP is a scarce resource and has a limited shelf life (14 days) after which it must be disposed of. The consequences of wastage are the opportunity cost of loss of overall treatment capacity across the NHS and reputational damage.The context was this feasibility study, set up to assess deliverability to RLH and subsequent wastage levels. Within this, we conducted a quality improvement project, which aimed to reduce the wastage of LD-RCP to no more than 8% (ie, 1 of the 12 units delivered per week).Over this 2-year period, we reduced wastage from a weekly average of 70%–27%. This was achieved over four improvement cycles. The largest improvement came from moving near-expiry LD-RCP to the emergency department (ED) for use with their trauma patients, with subsequent improvements from embedding use in ED as routine practice, introducing a dedicated LD-RCP delivery schedule (which increased the units ≤2 days old at delivery from 42% to 83%) and aligning this delivery schedule to cover two cycles of peak demand (Fridays and Saturdays).

Current management principles of hemorrhagic shock after trauma emphasize earlier transfusion therapy to prevent dilution of clotting factors and correct coagulopathy. London's Air Ambulance (LAA) was the first UK civilian prehospital service to routinely offer prehospital red blood cell (RBC) transfusion (phRTx). We investigated the effect of phRTx on mortality.Retrospective trauma database study comparing mortality before implementation with after implementation of phRTx in exsanguinating trauma patients. Univariate logistic regression was performed for the unadjusted association between phRTx and mortality was performed, and multiple logistic regression adjusting for potential confounders.We identified 623 subjects with suspected major hemorrhage. We excluded 84 (13.5%) patients due to missing data on survival status. Overall 187 (62.3%) patients died in the before phRTx period and 143 (59.8%) died in the after phRTx group. There was no significant improvement in overall survival after the introduction of phRTx (P = 0.554). Examination of prehospital mortality demonstrated 126 deaths in the pre-phRTx group (42.2%) and 66 deaths in the RBC administered group (27.6%). There was a significant reduction in prehospital mortality in the group who received RBC (P 0.001).phRTx was associated with increased survival to hospital, but not overall survival. The "delay death" effect of phRTx carries an impetus to further develop inhospital strategies to improve survival in severely bleeding patients.

Haemostasis is a complex process that ensures the maintenance of blood flow under normal physiological conditions and prevents major blood loss following vascular injury. The process is tightly regulated to prevent pathological thrombosis. Normal haemostasis relies on the delicate balance of prothrombotic and anticoagulant processes, where five components play a significant role in maintaining the haemostasis, these include: (1) endothelial cells; (2) platelets which are key to platelet plug formation; (3) coagulation factors that are essential to formation of insoluble fibrin clot; (4) coagulation inhibitors; and (5) fibrinolysis. This article will provide an overview of the current concepts of haemostasis, and through this we will explain how antiplatelets and antithrombotic drugs work, as well as provide a basic understanding of how to interpret clotting tests used to measure coagulation disorders.

The lack of antidotes for activated factor X‐inhibitor direct oral anticoagulants (DOACs) means that management of bleeding consists largely of existing supportive therapies. This study aimed to: (i) examine the relative frequency of DOAC‐related major bleeding in relation to DOAC prescriptions over the study period; (ii) describe the presentation and haematological management of DOAC‐related major bleeding; and (iii) evaluate the association between the use of prothrombin‐complex‐concentrate (PCC) and in‐hospital mortality. Over a 3‐year period, 32 UK hospitals submitted data on haematological management of DOAC‐related bleeding. Data consisted of 421 episodes (67%, 21%, 11% and 1% on rivaroxaban, apixaban, dabigatran and edoxaban respectively) of major bleeding on DOACs. The proportion of major bleeds on DOACs and DOAC prescriptions increased throughout the study. Overall, 44% and 37% of patients presented with gastrointestinal bleeding and intracranial haemorrhage (ICH) respectively. Drug concentrations were seldom measured. Compared to no PCC, there was a borderline evidence that receiving low dose PCC (≤25 iu/kg) was associated with better outcomes in terms of mortality (sub‐distribution hazard ratio: 0·15; 95% confidence interval: 0·02–1·19; P = 0·07): but this was not the case for higher doses. DOAC concentrations are seldom measured. There was no evidence of benefit for PCC on in‐hospital mortality.

Prolonged aPTT in Patients with Covid-19 In this study, 20% of patients with Covid-19 had a prolonged activated partial-thromboplastin time. In 90% of these cases, the cause was lupus anticoagulant...

There are no estimates of the heritability of phenotypic udder traits in suckler sheep, which produce meat lambs, and whether these are associated with resilience to mastitis. Mastitis is a common disease which damages the mammary gland and reduces productivity. The aims of this study were to investigate the feasibility of collecting udder phenotypes, their heritability and their association with mastitis in suckler ewes. Udder and teat conformation, teat lesions, intramammary masses (IMM) and litter size were recorded from 10 Texel flocks in Great Britain between 2012 and 2014; 968 records were collected. Pedigree data were obtained from an online pedigree recording system. Univariate quantitative genetic parameters were estimated using animal and sire models. Linear mixed models were used to analyse continuous traits and generalised linear mixed models were used to analyse binary traits. Continuous traits had higher heritabilities than binary with teat placement and teat length heritability (h2) highest at 0.35 (SD 0.04) and 0.42 (SD 0.04), respectively. Udder width, drop and separation heritabilities were lower and varied with udder volume. The heritabilities of IMM and teat lesions (sire model) were 0.18 (SD 0.12) and 0.17 (SD 0.11), respectively. All heritabilities were sufficiently high to be in a selection programme to increase resilience to mastitis in the population of Texel sheep. Further studies are required to investigate genetic relationships between traits and to determine whether udder traits predict IMM, and the potential benefits from including traits in a selection programme to increase resilience to chronic mastitis.\ud \ud

BACKGROUND: Prolongation of prothrombin time (PT) is often recorded in critical illness, but has limited ability to predict risk of bleeding. This exploratory study was aimed at assessing a role for thrombin generation (TG) to predict bleeding. STUDY DESIGN AND METHODS: TG was measured by Calibrated Automated Thrombography in admissions to intensive care with prolonged PT. Bleeding events were recorded up to day 5 after enrolment and correlated with results of PT ratio (PTR) and parameters of TG. RESULTS: 306 patients were recruited. 101 bleeding events developed in 46 patients during the period of observation. Many patients with prolonged PT had endogenous thrombin potential (ETP) which was within the normal range (120/251 patients, 47.8%) or even elevated (8%). Although some patients had a reduction in ETP or peak thrombin these were present over a wide range of PTR. There was no suggestion by Receiver operating characteristic (ROC) analysis that parameters of conventional TG were sensitive at predicting bleeding. No bleeding events were documented in patients defined as ETP-high, despite elevated PTR. CONCLUSION: Future studies need to explore a role for alternatives tests of coagulation in critical illness. Development of TG assays is required to positively identify more patients at increased bleeding risk or to exclude a larger number at low risk and how this relates to subgroups, such as patients with liver disease, and the need for prophylactic plasma transfusion. Trial registration-ISRCTN50516147Keywords: critical illness, coagulopathy, prothrombin time, thrombin generation, plasma transfusion

Introduction The benefit of administering chemical thromboprophylaxis to chronic kidney disease patients undergoing renal transplantation is unclear and no previous systematic review has addressed this as reflected by variations in national guidelines. Methods A literature search was performed using MEDLINE, Embase, Cochrane, CINAHL, World Health Organisation (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov databases to December 2019. Studies included participants undergoing renal transplantation only with no contra-indication to thromboprophylaxis, no history/clinical suspicion of acute organ rejection and those describing a form of chemical thromboprophylaxis intervention compared with another form, no intervention or placebo. Results Thirteen studies with 1600 patients were included. There was wide variation concerning type of thromboprophylaxis, time of onset, dosing and duration. Reports of symptomatic/asymptomatic venous thromboembolism and mortality were limited. Seven studies reported on renal allograft thrombosis. When comparing thromboprophylaxis to no intervention, there was no evidence of difference for thrombosis risk (risk ratio 0.2; [95% CI 0.01–4.63]), however all studies were underpowered to answer this question. Six studies reported on major bleeding but type of intervention, timing of onset and duration of thromboprophylaxis varied significantly, making it difficult to pool data for further analysis. Conclusion There is insufficient evidence to advise on efficacy and safety of chemical thromboprophylaxis in patients undergoing renal transplantation or to determine whether one chemical thromboprophylaxis is better than another thromboprophylaxis.

SUMMARYBackground Haemorrhage is the leading cause of mortality during trauma. In 2012, London's Air Ambulance introduced Blood on Board (BOB), transfusing group O red cells (RBC) to trauma patients at the scene. Objectives This study assessed the impact of BOB on the number of mixed field samples received by the laboratory, the number of group O RBC transfused to non-group O patients and the ratio of RBC to fresh frozen plasma (FFP) transfused in the initial 24 h. Methods Three major trauma centres collected data on patients for whom the major haemorrhage protocol was activated between August 2008 and February 2012 pre-BOB and March 2012 and December 2013 post-BOB. Results A total of 233 trauma patients were identified pre-BOB and 119 post-BOB. There was no significant difference in the percentage of group O units transfused to non-group O patients (75 vs 82%, P = 0·21) or the RBC : FFP ratio (pre-BOB mean 1·6 [interquartile range (IQR) 1·0–2·0]; post-BOB mean 1·7 [IQR 1·1–2·2], P = 0·24). There was no significant difference in the percentage of mixed field samples received (23% vs 27%, P = 0·3). Conclusion The introduction of BOB did not change the proportion of group O RBC transfused or the RBC : FFP ratio; however, the proportion of acceptable samples decreased. This is largely due to an increase in blood samples not received from the post-BOB cohort, which we believe is probably due to patients who died at the scene. We have introduced robust systems to indicate reasons for not obtaining samples.

Highlights • More severe claw horn lesions were associated with increased risk of future lameness. • More severe sole lesions were associated with reduction in daily yield of 2.68 kg. • Managing heifers to reduce severe lesions is likely to have positive herd impacts. • Mild claw horn lesions associated with reduced risk of future lameness and culling. • Mild insult may lead to adaptive changes in the hoof which are beneficial., The importance of lameness in primiparous dairy heifers is increasingly recognised. Although it is accepted that clinical lameness in any lactation increases the risk of future lameness, the impact of foot lesions during the first lactation on long-term lameness risk is less clear. This retrospective cohort study aimed to investigate the impacts of foot lesions occurring around the time of first calving in heifers on future lameness risk, daily milk yield and survival within a dairy herd. Records were obtained for 158 heifers from one UK dairy herd. Heifers were examined in 2 month blocks from 2 months pre-calving through to 4 months post-calving. Sole lesions and white line lesions were scored on a zero to 10 scale and digital dermatitis on a zero to 3 scale. Outcomes investigated were; lameness risk based on weekly locomotion scores, average daily milk yield and culling risk. Mixed effect models were used to investigate associations between maximum lesion scores and outcomes. Lesion scores in the highest score categories for claw horn lesions (sole lesions and white line lesions) in the 2 to 4 month post-calving period were associated with an increased risk of future lameness; heifers with white line lesion scores ≥3 compared with scores zero to 1 and heifers with sole lesion scores ≥4 compared with score 2, at this time point, had a predicted increased risk of future lameness of 1.6 and 2.6 respectively. Sole lesions ≥4 were also associated with a reduction in average daily milk yield of 2.68 kg. Managing heifers to reduce claw horn lesions during this time period post-calving may provide health, welfare and production benefits for the long-term future of those animals. A novel finding from the study was that mild lesion scores compared with scores zero to 1, were associated with a reduced risk of future lameness for white line lesions and sole lesions occurring in the pre-calving or 2 to 4 months post-calving periods respectively. Mild sole lesions in the pre-calving period were also associated with a reduced risk of premature culling. One hypothesis for this result is that a mild insult may result in adaptive changes to the foot leading to greater biomechanical resilience and so increased longevity.

A 2-year prospective, longitudinal study of 10 suckler sheep flocks in Great Britain was run to identify factors associated with acute mastitis (AM) and chronic mastitis, and their impact on lamb growth rate. Data were collected on AM, intramammary masses (IMM; a marker for chronic mastitis), udder and teat conformation, teat lesions, body condition, ewe nutrition, litter size, lamb weight and general flock management. Each flock was visited twice each year, approximately 4 weeks before lambing and 9 weeks into lactation, for two years and all ewes present at a visit were examined. There were 7021 examinations in total. AM was reported in 2.1–3.0% of ewes/year; this ranged from 0.0% to 37.1% by flock. IMM were detected in 4.7% of ewes in pregnancy and 10.9% of ewes in lactation. Once an IMM had been detected there was an increased risk of future IMM although IMM were not consistently present. The majority of ewes had good udder conformation to suckle lambs. Factors associated with AM, IMM in pregnant and lactating ewes, udder conformation and lamb daily live weight gain were explored using mixed effect multivariable models. An increased risk of AM was associated with underfeeding protein in pregnancy (OR 4.05), forward pointing teats (OR 2.54), downward pointing teats (OR 4.68), rearing ≥ 2 lambs (OR 2.65), non-traumatic teat lesions (OR 2.09); and marginally associated with the presence of IMM. An increased risk of IMM in lactation was associated with AM during lactation (OR 12.39), IMM in pregnancy (OR 4.79), IMM in the previous lactation (OR 4.77), underfeeding energy in pregnancy (OR 6.66) and traumatic teat lesions (OR 2.48). An increased risk of IMM in pregnancy was associated with IMM in the previous pregnancy, IMM in the previous lactation and underfeeding energy in the previous lactation (OR 2.95). Lower lamb daily live weight gain was associated with traumatic teat lesions, IMM in lactation (−0.01 kg/day) and AM (−0.04 kg/day). We conclude that inadequate nutrition is an important cause of mastitis in suckler ewes which farmers could address in part using current nutritional guidelines but further work is needed. The relationship between AM and IMM indicates that separating or culling ewes with IMM would help reduce AM.\ud

Granulomas and shelly hoof (SH), are lesions of sheep feet. Our objective was to use data from four questionnaires on lameness sent to English sheep farmers in 2004, 2013, 2014 and 2015 to further understanding of the risks and aetiologies of both lesions. Granulomas were more likely in flocks where routine foot trimming (odds ratio [OR] = 3.17; 95% confidence intervals [CI] 1.11–11.47) and routine footbathing (OR = 2.38; 95% CI 1.19–4.83) were practised than where these management protocols were not. SH was more likely in flocks that were footbathed in formalin compared with not footbathing (OR = 1.65; 95% CI 1.19–2.30), and was less common in flocks that stocked ewes at more than eight vs. four per acre (OR = 0.34; 95% CI 0.17–0.68). There were weak associations between SH and foot trimming. In 2004 only, SH was more likely in flocks where therapeutic foot trimming was practised than not practised (OR = 2.24; 95% CI 1.12–4.68). In 2014 only, SH was marginally less likely in flocks where no feet bled during trimming, compared with flocks not routinely trimmed (OR = 0.55; CI 0.30–1.00); SH was not related to foot trimming once severe footrot was included. We propose that flocks with granulomas and SH would decrease if farmers stopped footbathing in general, in particular with formalin, and avoided foot trimming whether as a therapeutic or routine practice. Further work is needed to understand the role of stocking density.

The outcomes of patients developing major bleeding while on oral anticoagulants remain largely unquantified. The objectives of this study were to: (i) describe the burden of major hemorrhage associated with all available oral anticoagulants in terms of proportion of bleeds which are intracranial hemorrhages, in-hospital mortality and duration of hospitalization following major bleeding; (ii) identify risk factors for mortality; and (iii) compare the characteristics of major hemorrhage between cases treated with warfarin and direct oral anticoagulants for the subgroups of patients with atrial fibrillation or venous thromboembolism. This was a multicenter, 3-year prospective cohort study of patients aged ≥18 years on oral anticoagulants who developed major hemorrhage leading to hospitalization. The patients were followed up for 30 days or until discharge or death, whichever occurred first. In total 2,192 patients (47% female, 81% on warfarin, median age 80 years) were reported between October 2013 and August 2016 from 32 hospitals in the UK. Bleeding sites were intracranial (44%), gastrointestinal (33%), and other (24%). The in-hospital mortality was 21% (95% CI: 19%-23%) overall, and 33% (95% CI: 30%-36%) for patients with intracranial hemorrhage. Intracranial hemorrhage, advanced age, spontaneous bleeding, liver failure and cancer were risk factors for death. Compared to warfarin-treated patients, patients treated with direct oral anticoagulants were older and had lower odds of subdural/epidural, subarachnoid and intracerebral bleeding. The mortality rate due to major bleeding was not different between patients being treated with warfarin or direct oral anticoagulants. Major bleeding while on oral anticoagulant therapy leads to considerable hospital stays and short-term mortality.

The aims of this study were to estimate the incidence rate of clinical mastitis (IRCM) and identify risk factors for clinical mastitis in suckler ewes to generate hypotheses for future study. A postal questionnaire was sent to 999 randomly selected English sheep farmers in 2010 to gather data on farmer reported IRCM and flock management practices for the calendar year 2009, of which 329 provided usable information. The mean IRCM per flock was 1.2/100 ewes/year (CI:1.10:1.35). The IRCM was 2.0, 0.9 and 1.3/100 ewes/year for flocks that lambed indoors, outdoors and a combination of both, respectively.\ud \ud Farmers ran a variety of managements before, during and after lambing that were not comparable within one model, therefore six mixed effects over-dispersed Poisson regression models were developed.\ud \ud Factors significantly associated with increased IRCM were increasing percentage of the flock with poor udder conformation, increasing mean number of lambs reared/ewe and when some or all ewes lambed in barns compared with outdoors (Model 1).\ud \ud For ewes housed in barns before lambing (Model 2), concrete, earth and other materials were associated with an increase in IRCM compared with hardcore floors (an aggregate of broken bricks and stones). For ewes in barns during lambing (Model 3), an increase in IRCM was associated with concrete compared with hardcore flooring and where bedding was stored covered outdoors or in a building compared with bedding stored outdoors uncovered. For ewes in barns after lambing (Model 4), increased IRCM was associated with earth compared with hardcore floors, and when fresh bedding was added once per week compared with at a frequency of ≤2 days or twice/week.\ud \ud The IRCM was lower for flocks where some or all ewes remained in the same fields before, during and after lambing compared with flocks that did not (Model 5). Where ewes and lambs were turned outdoors after lambing (Model 6), the IRCM increased as the age of the oldest lambs at turnout increased.\ud \ud We conclude that the reported IRCM is low but highly variable and that the complexity of management of sheep around lambing limits the insight into generating hypotheses at flock level for risks for clinical mastitis across the whole industry. Whilst indoor production was generally associated with an increased IRCM, for ewes with large litter size indoor lambing was protective, we hypothesise that this is possibly because of better nutrition or reduced exposure to poor weather and factors associated with hygiene.

Objective: To ascertain the incidence of massive transfusion (MT) in obstetrics in the UK, and describe its management and clinical outcomes. Design: A population‐based cross‐sectional study conducted through the UK Obstetric Surveillance System (UKOSS). Settings: All UK hospitals with consultant‐led maternity units. Population: Any pregnant woman at ≥20 weeks of gestation receiving ≥8 units of red blood cells within 24 hours of giving birth, from July 2012 to June 2013. Methods: Prospective case identification through the monthly mailing of UKOSS. Results: We identified 181 women who had undergone MT, making the estimated incidence of MT associated with postpartum haemorrhage (PPH) 23 per 100 000 maternities (95% confidence interval 19–26) per year. The median estimated blood loss was 6 l (interquartile range 4.5–8.0 l). The majority of women presented outside working hours (63%), 40% had had previous caesarean sections and 3% had normal vaginal births without risk factors. The main cause for MT was uterine atony (40%) and the main mode of birth was caesarean section (69%). Of the 181 women, 15 received >20 units of red blood cells. In total, 45% of women underwent hysterectomy, and among all causes of PPH, placenta accreta had the highest hysterectomy rate. Two women died, 82% were admitted to intensive care/high‐dependency units, and 28% developed major morbidities. Conclusion: Massive transfusion due to PPH is associated with high rates of morbidity and hysterectomy. Clinical and research efforts should focus on approaches to recognise and optimise timely resuscitation and management of these severe cases. Tweetable abstract: Massive transfusion due to postpartum haemorrhage is associated with high rates of morbidity and hysterectomy.

Acute mastitis in suckler ewes is often detected because of systemic signs such as anorexia or lameness, whereas chronic mastitis, characterized by intramammary abscesses with no systemic disease, is typically detected when ewes are inspected before mating. The aims of the current study were to identify the species and strains of culturable bacteria associated with acutely diseased, chronically diseased, and unaffected mammary glands to investigate whether species and strains vary by state. To investigate acute mastitis, 28 milk samples were obtained from both glands of 14 ewes with acute mastitis in one gland only. To investigate chronic mastitis, 16 ovine udders were obtained from 2 abattoirs; milk was aspirated from the 32 glands where possible, and the udders were sectioned to expose intramammary abscesses, which were swab sampled. All milk and swab samples were cultured aerobically. In total, 37 bacterial species were identified, 4 from acute mastitis, 26 from chronic mastitis, and 8 from apparently healthy glands. In chronic mastitis, the overall coincidence index of overlap of species detected in intramammary abscesses and milk was 0.60, reducing to 0.36 within individual glands, indicating a high degree of species overlap in milk and abscesses overall, but less overlap within specific glands. Staphylococcus aureus was detected frequently in all sample types; it was isolated from 10/14 glands with acute mastitis. In 5 ewes, closely related strains were present in both affected and unaffected glands. In chronic mastitis, closely related Staphylococcus aureus strains were detected in milk and abscesses from the same gland.

Background Low fibrinogen (Fg) concentrations in trauma haemorrhage are associated with poorer outcomes. Cryoprecipitate is the standard source for Fg administration in the UK and USA and is often given in the later stages of transfusion therapy. It is not known whether early cryoprecipitate therapy improves clinical outcomes. The primary aim of this feasibility study was to determine whether it was possible to administer cryoprecipitate, within 90 min of admission to hospital. Secondary aims were to evaluate laboratory measures of Fg and clinical outcomes including thrombotic events, organ failure, length of hospital stay and mortality. Methods This was an unblinded RCT, conducted at two civilian UK major trauma centres of adult trauma patients (age ≥16 yrs), with active bleeding and requiring activation of the major haemorrhage protocol. Participants were randomised to standard major haemorrhage therapy (STANDARD) (n=22), or to standard haemorrhage therapy plus two early pools of cryoprecipitate (CRYO) (n=21). Results 85% (95% CI: 69–100%) CRYO participants received cryoprecipitate within 90 min, median time 60 min (IQR: 57–76) compared with 108 min (67–147), CRYO and STANDARD arms respectively (P=0.002). Fg concentrations were higher in the CRYO arm and were maintained above 1.8 g litre−1 at all time-points during active haemorrhage. All-cause mortality at 28 days was not significantly different (P=0.14). Conclusions Early Fg supplementation using cryoprecipitate is feasible in trauma patients. This study supports the need for a definitive RCT to determine the effect of early Fg supplementation on mortality and other clinical outcomes. Trial registry number ISRCTN55509212.

This study investigated the effect of three dietary regimes for replacement gilts on lameness and carcass traits. Diets were: a diet specifically formulated for replacement gilts (diet 1, 14.0 MJ of DE/kg, 0.75% lysine), a finisher diet (diet 2, 13.5 MJ of DE/kg, 1.02% lysine) and a gestation sow diet (diet 3, 13.0 MJ of DE/kg, 0.69% lysine): the latter two diets are traditionally fed to replacement gilts. Thirty-six gilts were selected at day (d)0 (70.8 kg±0.78 SE, aged ~130d), housed individually and allocated at random to 1) DEV (restricted access diet 1, n=12), 2) FIN (ad-libitum access diet 2, n=12) or 3) GES (initially ad-libitum access diet 2, then restricted access to diet 3 from d30, n=12). All gilts were fed ad-libitum from d71–83. Locomotory ability (0=normal to 5=severely impaired) and limb lesions (0=normal to 3=severe) were scored weekly until d82. Hind-claw lesions and toe uneveness were scored (0=normal to 3=severe) at d0, 40 and 82. Gilts were weighed at d0, 28, 70 and 82. Carcass traits were recorded at slaughter (d83) and one front leg was removed for dual-energy X-ray absorptiometry (DXA) to establish areal bone mineral density (aBMD). Joint surface lesions of the humeral condyle (HC; 1=normal to 4=severe, 5=osteochondrosis dissecans) and anconeal process (AP; 1=absent 2=present) were scored. The percentage of lame animals (locomotion score ≥2) on ≥1 occasion were DEV=0% (0/11), FIN=73% (8/11) and GES=75% (9/12) (P

FOOTROT (interdigital dermatitis [ID] and under-running footrot) is an infectious dermatitis of sheep feet that results in both poor welfare and production losses. Footrot is present in more than 90 per cent of flocks (Winter and others 2015) and accounts for approximately 70 per cent of lameness in sheep in England. The cost to the UK sheep industry is estimated between £24 million and £80 million per annum (Nieuwhof and Bishop 2005, Wassink and others 2010). In 1941, Beveridge identified Dichelobacter nodosus as the causal agent of ovine footrot. Through experimental challenge he concluded that D nodosus alone was required for footrot to occur but the disease was more severe when other bacterial species including Fusobacterium necrophorum and spirochaetes were present. More recent research has confirmed that D nodosus has virulence factors (Type IV fimbriae and AprV2 protease) that are essential for the occurrence of footrot (Kennan and others 2001, 2010). Later studies of disease pathogenesis reported that F necrophorum was the causal agent of ID, and that the presence of F necrophorum was required before colonisation with D nodosus could occur (Roberts and Egerton 1969). This led to the concept that ID, also known as scald, and under-running footrot were two separate disease conditions, with ID making sheep more susceptible to under-running footrot (Grogono-Thomas and Johnston 1997, Winter 2004). This concept was widely believed and stated in veterinary textbooks, expert articles and information provided to farmers (Winter 2004, Abbott and Lewis 2005). The advent of molecular techniques has allowed further investigation of …

Background: The lack of antidotes for direct-oral-anticoagulants (DOACs) means that management of bleeding on DOACs will consist largely of existing therapies. This study aimed to: a) examine the relative frequency of DOAC-related major bleeding in relation to DOAC prescriptions over study period; b) describe the presentation and haematological management of DOAC-related major bleeding; and c) evaluate the association between use of prothrombin-complex-concentrate (PCC) and in-hospital mortality. Methods: Over a three-year period (2013-2016) 32 UK hospitals submitted routine data on haematological management of DOAC-related bleeding. Findings: Data consisted of 421 episodes (67%, 21%, 11% and 1% on rivaroxaban, apixaban, dabigatran and edoxaban respectively) of major bleeding on DOACs. The proportion of major bleeds on DOAC and DOAC prescriptions increased throughout the study. Overall, 44% and 37% of patients presented with gastrointestinal bleeding and intracranial-haemorrhage (ICH) respectively. Factor-specific assays were seldom performed. PCC was the most common treatment (39%) and was more likely to be given for ICH and factor-Xa inhibitor DOACs. Compared to no PCC, receiving ≥3000 IU of PCC was associated with over twofold increase in adjusted cumulative incidence of death (subdistribution hazard ratio: 2.56; 95%CI: 1.46-4.47; p=0.001); there were no statistically significant associations with lower doses. The in-hospital thromboembolic event rate was 1.9% and was not associated with PCC use. Interpretation: There was no evidence of benefit associated with PCC use for major bleeding DOAC patients in terms of in-hospital mortality, and higher doses were associated an increased incidence of death; PCC effects should be further investigated. Funding: The study was funded by the British Society for Haematology Early Stage Researcher Fellowship awarded to Dr Laura Green. Declaration of Interest: All authors declare the following: LG, JT, JM, NC, TE and SS have no conflicts of interest to disclose. AS has received honorarium from from Bayer Healthcare, Daiichi Sankyo, and Portola, outside the submitted work. RA has received honorarium from Bayer, Daiichi-Sankyo, Boehringer Ingelheim and BMS/Pfizer. KS has received honorarium from Bayer, BMS/Pfizer and Boehringer Ingelheim. CT has received honoraria and/or support to attend scientific meetings from Bayer, Pfizer, NovoNordisk, Shire, Sobi, CSL Behring and Daiichi-Sankyo. PM has served as a speaker for Bayer and Daiichi-Sankyo, as a consultant for Daiichi-Sankyo, and has received travel support from Boehringer Ingelheim. Ethical Approval: Ethics approval was obtained for the study from the National Health Service, Health Research Authority (East of England- Cambridge South Research Ethics Committee, reference: 12/EE/0431)

Highlights • Investigate the role of D. nodosus and F. necrophorum in the progression of ovine FR. • Markovian model developed using bacterial load and disease severity. • The model generates probabilistic forecasts one week ahead. • All 34 rates between the 12 states of an individual foot are time homogeneous. • Results suggest primary role of D. nodosus in the initiation and progression of footrot. • Results suggest a secondary role of F. necrophorum only in severely diseased feet., Dichelobacter nodosus is a virulent, invasive, anaerobic bacterium that is believed to be the causative agent of ovine footrot, an infectious bacterial disease of sheep that causes lameness. Another anaerobe, Fusobacterium necrophorum, has been intimately linked with the disease occurrence and severity. Here we examine data from a longitudinal study of footrot on one UK farm, including quantitative PCR (qPCR) estimates of bacterial load of D. nodosus and F. necrophorum. The data is at foot level; all feet were monitored for five weeks assessing disease severity (healthy, interdigital dermatitis (ID), or severe footrot (SFR)) and bacterial load (number of bacteria/swab). We investigate the role of D. nodosus and F. necrophorum in the progress of the disease using a continuous-time Markov model with 12 different states characterising the foot. The transition rates between the adjacent states are the (34) model parameters, these are determined using Metropolis Hasting MCMC. Our aim is to determine the predictive relationship between past and future D. nodosus and F. necrophorum load and disease states. We demonstrate a high level of predictive accuracy at the population level for the D. nodosus model, although the dynamics of individual feet is highly stochastic. However, we note that this predictive accuracy at population level is only high in more diseased states for F. necrophorum model. This supports our hypothesis that D. nodosus load and status of the foot work in combination to give rise to severe footrot and lameness, and that D. nodosus load plays the primary role in the initiation and progression of footrot, while F. necrophorum load rather increases disease severity of SFR.

Lameness in sheep has economic and welfare implications, including loss of ewe body condition, lower lambing percentages, and poor lamb growth rates. It costs the UK sheep industry around £80 million per year. The majority of lameness is caused by the infectious diseases footrot and contagious ovine digital dermatitis, with white line separation, white line abscesses, and toe granulomas also reported by farmers. Most sheep farmers in the UK have other enterprises and care for their flock part-time. A lameness control plan (LCP) consisting of 37 management practices that covered all aspects of control of lameness was developed for part-time sheep farmers. Testing of the LCP was done using a stepped-wedge trial design with 7 visits to 44 flocks in England over 18 months. Flocks had 100–500 breeding ewes. Locomotion scoring was carried out at every visit, and farmers were interviewed every 6 months to record management practices. Clinical significance of changes in prevalence of lameness within each flock was analysed using the reliable change index (RCI). Management practices associated with prevalence of lameness were assessed using a multi-level multivariable over-dispersed Poisson model. The geometric mean (GM) prevalence of lameness at the start of the trial was 7.3% (95% confidence interval(CI) = 6.3–8.3%). Flocks with a clinically significant lameness reduction had a GM prevalence of lameness of 4.6% (95% CI = 4.1–5.2%), while flocks with a clinically significant increase in lameness had a GM prevalence of 10.5% (95% CI = 9.4–11.6%). Always separating lame sheep at treatment (relative risk (RR) = 0.60, 95% CI = 0.43-0.84) and culling sheep lame ≥2 occasions in a year (RR = 0.75, 95% CI = 0.61-0.92) were associated with a significant reduction in lameness. Compared with not footbathing at all, footbathing sheep when there were outbreaks of interdigital dermatitis reduced lameness (RR = 0.85, 95% CI = 0.75-0.96), however, ‘routine’ footbathing was not associated with a reduction in lameness. Housing during the previous lambing period was associated with a higher prevalence of lameness (RR = 1.23, 95% CI = 1.04–1.46). Vaccination in flocks with period prevalence ≥10% did not significantly reduce their risk of lameness compared to lower prevalence flocks. In conclusion, separating lame sheep at treatment, culling sheep lame ≥2 occasions per year, and only using a footbath to treat outbreaks of interdigital dermatitis are flock managements that contribute to improved control of lameness in flocks with part-time farmers.

A prospective longitudinal study was carried out on 39 outdoor breeding pig farms in England in 2003 and 2004 to investigate the risks associated with mortality in liveborn preweaning piglets. Researchers visited each farm and completed a questionnaire with the farmer and made observations of the paddocks, huts and pigs. The farmer recorded the number of piglets born alive and stillborn, fostered on and off and the number of piglets that died before weaning for 20 litters born after the visit. Data were analysed from a cohort of 9424 liveborn piglets from 855 litters. Overall 1274 liveborn piglets (13.5%) died before weaning. A mixed effect binomial model was used to investigate the associations between preweaning mortality and farm and litter level factors, controlling for litter size and number of piglets stillborn and fostered. Increased risk of mortality was associated with fostering piglets over 24h of age, organic certification or membership of an assurance scheme with higher welfare standards, farmer's perception that there was a problem with pest birds, use of medication to treat coccidiosis and presence of lame sows on the farm. Reduced mortality was associated with insulated farrowing huts and door flaps, women working on the farm and the farmer reporting a problem with foxes.

Summary Major obstetric haemorrhage (MOH) remains an important medical challenge worldwide, contributing to significant maternal morbidity and mortality. Prompt and appropriate management is essential if we are to improve outcomes and reduce substandard care that may result in adverse consequences. This review describes the current understanding of the pathophysiological aspects of MOH together with the principles of transfusion and haemostatic therapy, with emphasis on a coordinated multidisciplinary approach. We also highlight the current lack of evidence available from randomized controlled trials to inform best practice and the need to prioritize research in this key clinical area.

This study evaluated the influence of floor type on sow welfare with particular focus on lameness, claw lesions (CL), and injuries. The study used 164 gilts housed in groups of 8 from AI to 110 d of pregnancy in pens with concrete (n = 84) slatted floor left uncovered or covered by 10-mm rubber slat mats (n = 80) through 2 parities. Lameness (0 = normal to 5 = severe), limb (0 = normal to 6 = severe) and body (0 = normal to 5 = severe) lesions, and manure on the body (MOB; score 0 to 2) were recorded at AI, 24 to 72 h postmixing, between 50 and 70 d of pregnancy, and 2 wk before farrowing. Claw lesions (score 0 = normal to 3 = severe) were recorded at AI and between 50 and 70 d of pregnancy. The dirtiness and wetness of the floors was scored weekly (score 0 = clean to 4 = >75% of the pen soiled/wet). Data from the first and second parities were analyzed separately. Sows were categorized as nonlame (score ≤ 1) or lame (score ≥ 2). Median (M e ) scores were calculated for CL and body and limb lesions and were classified as less than or equal to the median or greater than the median lesion scores. Sows on rubber slat mats had a reduced risk of lameness during both parities (P < 0.01) compared with sows on concrete. They also had an increased risk of scores greater than the median for toe overgrowth (M e = 2 and M e = 3 in the first and second parity, respectively) and heel sole crack (HSC; M e = 3) during both parities (P < 0.01) and for cracks in the wall (CW; M e = 4) and white line damage (WL; M e = 4; P < 0.01) in the first and second parity, respectively. There was a reduced risk of lameness in sows with scores greater than the median for HSC (P = 0.05) in the first parity and WL (M e = 3; P < 0.01) and CW (M e = 3; P < 0.05) in the second parity. Wounds (M e = 3) and severe lesions (M e = 0) on the limbs with scores greater than the median were associated with an increased risk of lameness (P < 0.01) in the first and second parity, respectively. Sows on rubber slat mats had a reduced risk of scores greater than the median for swellings (M e = 4) and wounds (P < 0.01) during both parities. Pens with rubber slat mats were dirtier than uncovered pens (P < 0.01); however, there was no association between MOB and flooring type. There was also no association between body lesion score and flooring type. In this study, CL were not associated with an increased risk of lameness. Therefore, even though rubber slat mats were associated with an increased risk of CL, they improved the welfare of group housed sows by reducing the risk of lameness and limb lesions.

A multi-species model that incorporates the transmission of both major and minor mastitis pathogens as well as the interaction between them via coinfection of a quarter is fitted to data from seven dairy herds. The results suggest that major and minor pathogens can interact, on occasion, in a counter-intuitive way with implications for the control of clinical mastitis. The key finding is that delaying culling of cows with major pathogen infections for more than 100 days post infection could result in a higher prevalence of major pathogen infections, whereas early culling would reduce the levels. A theoretical exploration of current and proposed control strategies is carried out, informed by parameters estimated from the model and data. The results at each stage suggest of areas of further research such as: field-testing of the hypotheses presented; the exploration of a stochastic formulation of the model; analysis of the raw repeated measures data; application of control theory to determine the most effective combination of control strategies; inclusion of economic factors into the modelling framework.

© 2016 International Society for Microbial Ecology All rights reserved. Pulmonary symptoms in cystic fibrosis (CF) begin in early life with chronic lung infections and concomitant airway inflammation leading to progressive loss of lung function. Gradual pulmonary function decline is interspersed with periods of acute worsening of respiratory symptoms known as CF pulmonary exacerbations (CFPEs). Cumulatively, CFPEs are associated with more rapid disease progression. In this study multiple sputum samples were collected from adult CF patients over the course of CFPEs to better understand how changes in microbiota are associated with CFPE onset and management. Data were divided into five clinical periods: pre-CFPE baseline, CFPE, antibiotic treatment, recovery, and post-CFPE baseline. Samples were treated with propidium monoazide prior to DNA extraction, to remove the impact of bacterial cell death artefacts following antibiotic treatment, and then characterised by 16S rRNA gene-targeted high-throughput sequencing. Partitioning CF microbiota into core and rare groups revealed compositional resistance to CFPE and resilience to antibiotics interventions. Mixed effects modelling of core microbiota members revealed no significant negative impact on the relative abundance of Pseudomonas aeruginosa across the exacerbation cycle. Our findings have implications for current CFPE management strategies, supporting reassessment of existing antimicrobial treatment regimens, as antimicrobial resistance by pathogens and other members of the microbiota may be significant contributing factors.

Activated protein C resistance (APCR) within a thrombin generation test (TGT) system is associated with an increased risk of venous thromboembolism (VTE). However, application of the TGT is restricted by the analytical platforms used to monitor thrombin generation. Using a routine coagulation analyser we have developed an automated chromogenic TGT that is sensitive to defects in the protein C pathway.The TGT was performed on a TOP500 analyser, in the presence and absence of Protac. The reaction was monitored using a substrate with slow kinetics for thrombin (S-2444). Results were expressed as the area under the curve normalised ratio (AUCnr). Assay results were compared with Coatest APCR (expressed as APC-ratio [CoAPCr]).Samples were obtained from 35 healthy subjects and 91 patients with previous history of VTE. Of these patients, 19, 17, and 9 had heterozygous factor V Leiden (FVL), antiphospholipid syndrome (APS), and protein C/protein S deficiencies (PC/PS) respectively.Inter-assay imprecision in the presence and absence of Protac were 20% and5% respectively. There was a significant difference between the AUCnr of normals (median [IQR]: 2.8 [2.4-4.7]) compared to: FVL (1.0 [0.7-1.2]); PC/PS (1.1 [0.9-1.2]); and APS (1.1 [0.8-1.4]); p0.001 for each comparison. No significant difference was seen between the AUCnr of normals and other VTE patients. The detection rate of AUCnr and CoAPCr were: 100% and 56% for FVL; 88% and 44% for PC/PS; and 64% and 45% for APS respectively.The automated TGT exhibited good sensitivity to defects in the protein C pathway.

In the final year of a three-year study of lameness in dairy cattle, 40 herds were allocated to either an intervention (22) or control (18) group. Farms in the intervention group were visited by a veterinarian who made up to 16 recommendations to reduce the incidence of lameness based on potential risks for lameness observed at that visit. Farms in the control group were visited and the same observations were made, but no changes recommended. All farms were visited on three further occasions to score the locomotion of all cows and collect information on changes made to the farm. Before intervention, the mean herd size, lactation average milk yield per cow and prevalence of severely lame cows were 122, 8,157 I and 9.85% for the control group and 109, 7,807 I and 9.14% for the intervention group. After the intervention there were no significant differences between the treatments in terms of the change in prevalence of severely lame cows or the change in rate of sole ulcer, white line disease or digital dermatitis. The overall uptake of recommendations was 41.3%. There were no significant correlations between the percentage of risks addressed and the rate of sole ulcer or prevalence of severely lame cows and only a non-significant trend for white line disease. Improvements to cubicle dimensions were associated with a reduction in the rate of sole ulcer, and changing nutrition and adding biotin to the ration were associated with a reduction in white line disease. Conversely, increasing the amount of sawdust to cubicle floors was associated with increased rate of sole ulcer and white line disease and improving cubicle dimensions was associated with increased rate of white line disease.

This review article summarises the evidence for an effective management protocol for footrot to sheep, the welfare and economic benefits of such a protocol and its likely uptake by farmers. Over 90% of lameness in sheep in England is caused by Dichelobacter nodosus, the aetiological agent of footrot. Farmers can recognise lame sheep both from video clips and when examining their own sheep but make a separate decision about whether to catch lame sheep. Only farmers who catch and treat mildly lame sheep immediately report a low prevalence of lameness (< 5%). From a within-farm clinical trial, treatment of sheep lame with footrot with parenteral antibiotic and topical spray led to over 90% recovery from lameness within 10 days whilst only 25% of sheep treated with foot trimming and topical spray recovered in 10 days. In parallel, a within-farm clinical trial with approximately 800 ewes was run for 18 months to test the hypothesis that rapid appropriate treatment led to reduced prevalence of lameness. Ewes were stratified and randomly allocated to one of two groups. The prevalence and incidence of lameness decreased in the treatment group, where lame sheep were treated with parenteral and topical antibacterials within three days of being observed lame, but remained at approximately 8% in the control group where lame sheep were treated with trimming hoof horn and topical antibacterial spray when the farm shepherd considered them sufficiently lame. Sheep in the treatment group had a higher body condition and produced more lambs that grew faster. The net economic benefit to all sheep (whether lame or not) in 2006 was £6 per ewe put to the ram. A group of 265 farmers were asked about their satisfaction with methods to manage footrot. Satisfied farmers reported a prevalence of lameness of ≤ 5% and used rapid individual treatment. Dissatisfied farmers reported a prevalence of lameness of > 5% and used whole-flock footbathing and vaccination. Overall, farmers stated that their ideal managements would be footbathing and vaccination. One explanation for this apparent inconsistency is that farmers want effective vaccines and footbaths; an alternative explanation is that this is an example of cognitive dissonance, where subjects adopt a belief because it is their current practice despite evidence that it is not effective. We conclude that farmers can identify lame sheep and that rapid treatment of individual sheep lame with footrot with intramuscular and topical antibacterials is currently the most effective control of interdigital dermatitis and footrot in sheep but that in future effective measures that prevent footrot would be ideal.

Farmers can recognise even mildly lame sheep and are reasonably accurate at estimating the prevalence of lameness in their flocks but make a separate decision on whether to treat lame sheep. Those who are treating individual lame sheep promptly and appropriately have a median prevalence of lameness of

We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H) and interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR-affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR, respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified because of mismatches in the 16S rRNA universal forward primer (27F). A specific real-time PCR assay was used to demonstrate the presence of D. nodosus, which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (10(4)-10(9) cells per g tissue) than those with H or VFR feet.

P>Total hip/knee replacement surgeries are associated with an increased risk of venous thromboembolism and post-operative thromboprophylaxis has become standard treatment. This study aimed to: (i) assess the impact of hip/knee replacement surgery on ex vivo thrombin generation (TG), prothrombin fragments 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT) and D-dimer; (ii) compare the anticoagulant effects of dalteparin and rivaroxaban on TG 24 h after surgery. Haemostatic variables were assessed in plasma samples of 51 patients taken pre-operatively, peri-operatively, and 24 h post-operatively. Prophylaxis, once a day, with dalteparin or rivaroxaban, starting 6-8 h post-operatively, was administered in 25 (14 knee/11 hip) and 26 patients (13 knee/13 hip) respectively. TG, F1 + 2, TAT and D-dimer increased during surgery. Dalteparin patients showed a variable TG response 24 h after surgery: conversely, the effect of rivaroxaban on TG was consistent across individuals. Good correlation was seen between rivaroxaban levels and TG-lag-time (rs = 0 center dot 46, P = 0 center dot 01); TG-time-to-Peak (rs = 0 center dot 53, P = 0 center dot 005); TG-peak-thrombin (rs = -0 center dot 59, P = 0 center dot 001); and TG-velocity-index-rate (rs = -0 center dot 61, P = 0 center dot 0009). Patients who received rivaroxaban showed a greater decrease of TG, F1 + 2 and TAT (but not D-dimer) than those on dalteparin. TG increases during hip/knee replacement surgery. Rivaroxaban inhibits TG more than dalteparin at 24 h after surgery.

Bovine tuberculosis (bTB) is caused by Mycobacterium bovis. The disease has a long latent period, heterogenous spread, can infect many species and can persist in the environment. In the UK, the rate of herd breakdowns (HBD) with bTB is increasing. A retrospective cohort study of 148 cattle herds was set up to investigate risk factors for HBD from October 2001 to November 2004. Herds were selected from farms located in the randomised badger culling trial (RBCT) and comprised holdings (24%) that were restocked with cattle after the foot and mouth disease (FMD) epidemic in 2001 and holdings (76%) that were continuously stocked throughout the FMD epidemic. Farmers were interviewed between June 2003 and February 2004. Questions on herd and farm management were asked for the period October 2001 to June 2003. Data on herd testing for bTB were sourced from the VetNet database and historic data from 1995 were used in the analysis. A discrete time survival analysis was used to examine factors associated with the risk of HBD.\ud \ud By the end of the study period. November 2004, 50% of study herds had experienced a HBD with bTB at least once. Farms that were restocked for less than 1 year after FMD had a reduced risk of HBD (P < 0.01) compared with continuously stocked farms in the same year. This reduced risk did not persist after 1 year of restocking. Feeding vitamin and mineral lick supplements compared with not feeding these supplements also reduced the risk of HBD. Factors associated with an increased risk of HBD were storing manure and slurry indoors or in a closed container, spreading manure all year round, herds with dairy cattle compared with herds without dairy cattle, increasing herd size, purchase of cattle from markets, location of the farm in the proactive area of the RBCT compared with survey only and location of farms in Somerset and North Devon.\ud \ud The lower risk of HBD in the first year after restocking but not the second or third year suggests that removal of all cattle might have lowered the infectious load of M. bovis on these premises for a period of time but that this did not persist once cattle were reintroduced. Purchase of cattle from markets suggests that there was a risk of introduction or re-introduction of bTB from these cattle. Method of storage or lack of storage of slurry might aid persistence of M. bovis in the environment if M. bovis survives in slurry in some circumstances.

The widespread use of central neuraxial block (CNB) and the prevalence of anticoagulation for different indications have led to an inevitable overlap between the two. The most serious complication of CNB in anticoagulated patients is the risk of spinal/epidural haematoma. Performing CNB in these patients is a complex decision that should take into account the twin risks of bleeding and venous/arterial thrombosis if anticoagulation therapies were to be stopped. Various guidelines have been issued to achieve normal haemostasis and thus allow safe administration of CNB. However, the evidence base for many such recommendations is weak, relying mainly on case reports, small studies and pharmacokinetics of the drugs. Given these limitations it is crucial to fully assess individual risk factors and understand anticoagulant pharmacokinetics in order to appropriately set time intervals for catheter insertion/removal. This paper will review traditional and newer anticoagulation/antiplatelet therapies with a view to improving the management of anticoagulated patients undergoing CNB.

Retroviral and transposon-based mutagenesis screens in mice have been useful for identifying candidate cancer genes for some tumor types. However, many of the organs that exhibit the highest cancer rates in humans, including the prostate, have not previously been amenable to these approaches. This study shows for the first time that the Sleeping Beauty transposon system can be used to identify candidate prostate cancer genes in mice. Somatic mobilization of a mutagenic transposon resulted in focal epithelial proliferation and hyperplasia in the prostate. Efficient methods were established to identify transposon insertion sites in these lesions, and analysis of transposon insertions identified candidate prostate cancer genes at common insertion sites, including Pde4d. PDE4D was also overexpressed in human prostate cancer patient samples and cell lines, and changes in PDE4D mRNA isoform expression were observed in human prostate cancers. Furthermore, knockdown of PDE4D reduced the growth and migration of prostate cancer cells in vitro, and knockdown of PDE4D reduced the growth and proliferation rate of prostate cancer xenografts in vivo. These data indicate that PDE4D functions as a proliferation promoting factor in prostate cancer, and the Sleeping Beauty transposon system is a useful tool for identifying candidate prostate cancer genes. [Cancer Res 2009;69(10):4388–97]

Claw lesion treatment records were recorded by farmers on 27 dairy farms (3,074 cows, 36,432 records) in England and Wales between February 2003 and February 2004. These were combined with farm environment and management data collected using a combination of direct observations, interviews with farmers, and milk recording data. Multilevel models were constructed for the 3 most frequently reported lesions related to lameness, namely, sole ulcers, white line disease, and digital dermatitis. Risks associated with an increased incidence of sole ulcers were parity 4 or greater, the use of roads or concrete cow tracks between the parlor and grazing, the use of lime on free stalls, and housing in free stalls with sparse bedding for 4 mo or more. The risks for white line disease were increasing parity and increasing herd size, cows at pasture by day and housed at night, and solid grooved concrete floors in yards or alleys. Solid grooved flooring was also associated with an increased risk of digital dermatitis, and cows 6 or more months after calving had a decreased risk of a first case of digital dermatitis. These results improve our understanding of the specific risks for 3 important lesions associated with bovine lameness and could be used as interventions in future clinical studies targeted at the reduction of specific lesions.

Between December 2002 and April 2006, 114 cattle farms in the south west of England were visited at least once, with 100 farms visited three times. A total of 29,782 serum samples were collected from 15,736 individually identified cattle. The sera were tested for the presence of antibodies against Mycobacterium avium subsp. paratuberculosis (MAP) using an indirect enzyme-linked immunosorbent assay (ELISA). The mean seroprevalence in herds sampled three times was 7.1%; 10.1% of cattle had at least one positive result. There were 78%, 75% and 75% dairy herds with at least one positive bovine at the first, second and third routine visits, respectively. In comparison, 44%, 42% and 46% suckler herds had at least one positive bovine for the first, second and third routine visits, respectively. In most herds (90%), within herd seroprevalence of MAP remained stable over time. Markov chain Monte Carlo (MCMC) simulation methods were used to re-estimate the test sensitivity and specificity. The sensitivity results were 33.3% (95% CI, 28.8-37.8%), 34.5% (95% CI, 30.3-38.8%) and 34.8% (95% CI, 30.8-38.9%) for the first, second and third routine visits and the specificity results were 99.7% (95% CI, 99.3-99.9%), 99.8% (95% CI, 99.4-99.9%) and 99.7% (95% CI, 99.3-99.9%) for the first, second and third routine visits, respectively. The expected true prevalence was also estimated, 11 (21.1%) suckler herds and 1 (2.1%) dairy herd were predicted to be truly free from infection during the study period. The seroprevalence of antibodies against MAP increased with cattle age. There was a significantly higher seroprevalence of MAP in dairy breeds of cattle compared with suckler breeds of cattle. This was more pronounced in Channel Island breeds. Smaller dairy herds (100 cattle) had a relatively lower seroprevalence of MAP than dairy herds with/=100 cattle. In 8 (42%) of the 19 herds withor =100 cattle born into the same herd, seropositive cattle were clustered by birth month whilst in the remaining herds clustering was not apparent. Daughters were significantly more likely to be MAP seropositive when born to a seropositive dam.

STAGE 1 MAKE THE CORRECT DIAGNOSIS (SPEAK A COMMON LANGUAGE) The common foot conditions are interdigital dermatitis (ID) (Fig. 2), footrot (FR) (Fig. 3), contagious ovine digital dermatitis (CODD) (Fig. 4), toe granuloma (Fig. 5), toe abscess (Fig. 6) and shelly hoof (Fig. 7) (illustrated and described at www.warwick.ac.uk/go/sheeplameness). In recent work at Warwick we highlighted that not all farmers

The foot and mouth disease (FMD) epidemic of 2001 was used to investigate herd breakdown (HBD) with bovine tuberculosis (bTB) in totally restocked herds of cattle. By August 2004, 2941 restocked cattle herds, with cattle movements from before and after 2001, had been tested for bTB for the first time since restocking. A total of 6% (177) of these herds broke down at the first bTB test. A binomial logistic regression model with HBD (at least one reactor bovine) at the first test after restocking as the outcome was used to investigate risks associated with HBD. The final model contained three risk factors. There was an increased risk for HBD in restocked herds with every log increase in herd size with an OR=1.38 (CI 1.16-1.64) to a maximum OR of 10.75. When there was a history of bTB on the restocked farm before 2001 the OR, with CI not including unity, were 5.92, 4.63, 3.8 and 2.9 for last HBD in 2000, 1999, 1998 and 1997, respectively, indicating a persistence in increased risk for restocked herds from farms with a history of HBD in the previous herd before restocking, i.e. a different population of cattle. Finally, for every log increase in the number of cattle purchased from herds with a greater than biennial frequency of testing for bTB in the previous 8 years (i.e. perceived high risk herds for bTB) there was an OR=1.35 (95% CI 1.22-1.49). The maximum OR was 9.27. These results indicate that both introduction of bTB through the purchase of cattle from farms with a high perceived risk of bTB infection and persistence of bTB on the restocked farm, (not the farm's original herd), were associated with an increased risk of HBD in the newly formed herds after restocking.

A cross-sectional study of 93 farms in England was carried out to estimate the prevalence and associated risk factors for bursitis. A total of 6250 pigs aged 6-22 weeks were examined for presence and severity of bursitis. Details of pen construction, pen quality and farm management were recorded including floor type, presence of bedding, condition of the floor and floor materials. The prevalence of bursitis was 41.2% and increased with each week of age (OR 1.1). Two-level logistic regression models were developed with the outcome as the proportion of pigs affected with bursitis in a pen. Pigs kept on soil floors with straw bedding were used as the reference level. In comparison with these soil floors, bursitis increased on concrete floors where the bedding was deep throughout (OR 4.6), deep in part (OR 3.7), and sparse throughout (OR 9.0), part slatted floors (OR 8.0), and fully slatted floors (OR 18.8). Slip or skid marks in the dunging area (OR 1.5), pigs observed slipping during the examination of the pen (OR 1.3) and wet floors (OR 3.6) were also associated with an increased risk of bursitis. The results indicate that bursitis is a common condition of growing pigs and that the associated risk factors for bursitis were a lack of bedding in the lying area, presence of voids and pen conditions which increased the likelihood of injury.

The milk yields of 1824 cows were used to investigate the effect of lesion-specific causes of lameness, based on farmer treatment and diagnosis of lame cows, on milk yield. A three-level hierarchical model of repeated test day yields within cows within herds was used to investigate the impact of lesion-specific causes of lameness (sole ulcer, white line disease, digital dermatitis and other causes) on milk yield before and after treatment compared with unaffected cows. Cattle which developed sole ulcer (SU) and white line disease (WLD) were higher yielding cattle before they were diagnosed. Their milk production fell to below that of the mean of unaffected cows before diagnosis and remained low after diagnosis. In cattle which developed digital dermatitis (DD) there was no significant difference in milk yield before treatment and a slightly raised milk yield immediately after treatment. The estimated milk loss attributable to SU and WLD was approximately 570 and 370 kg, respectively. These results highlight that specific types of lameness vary by herds and within herds they are associated with higher yielding cattle. Consequently lesion-specific lameness reduction programmes targeting the cow and farm specific causes of lameness might be more effective than generic recommendations. They also highlight the importance of milk loss when estimating the economic impact of SU and WLD on the farms profitability.

Caseous lymphadenitis (CLA) is an infectious disease of sheep caused by Corynebacterium pseudotuberculosis. It is prevalent in most sheep producing countries and was introduced into the UK sheep population in 1991. The pathogen invades the host through epithelium and forms an abscess in the local draining lymph node. Typically, disease presents as clinical, with overt (externally visible) swollen lymph nodes (the parotid, submandibular, prefemoral, prescapular, popliteal or mammary) or sub-clinical, with abscesses in the lungs and associated thoracic (bronchial and mediastinal) lymph nodes. We present a mathematical model in which disease is categorised as overt and/or respiratory (sub-clinical), using the above groupings. In both situations sheep may be infected and may or may not be infectious. In the model, overt abscesses may resolve and respiratory abscesses are considered to be present for life. Using the location of the abscesses, three routes of transmission are postulated: overt to overt, respiratory to overt and respiratory to respiratory. Data from four naturally infected flocks were used to describe populations of sheep with epidemic CLA and to estimate transmission coefficients for each of the postulated transmission routes. The infection process parameters were derived from literature where possible. Parameters were estimated using maximum likelihood methods and compared to the data using a multinomial distribution. The distribution of abscesses in the flocks was similar to endemic data reported in other studies. In the model most infected sheep developed abscesses, and approximately 36% of sheep with overt abscesses recovered from infection. The average time for respiratory abscesses to become infectious was 41 days. In these data, overt to overt transmission was the most frequent route of transmission since it had the highest coefficient in the model compared with respiratory to overt and respiratory to respiratory transmission. Transmission coefficients specific for each flock significantly (P < 0.05) improved the model fit to the data. In simulations using values of best-fitting parameter combinations, the proportion of sheep infected was between 0.39 and 0.60 at equilibrium. This is the first mathematical model of C. pseudotuberculosis infection, the parameter estimates indicate that aspects of the infection process could be utilised to design control strategies.