Every minute counts: A comparison of thawing times and haemostatic quality of plasma thawed at 37°C and 45°C using four different methods.

BACKGROUND: Having faster plasma thawing devices could be beneficial for transfusion services, as it may improve the rapid availability of thawed plasma for bleeding patients, and it might remove the need to have extended pre-thawed plasma: thus, reducing unnecessary plasma wastage. STUDY DESIGN AND METHODS: The aims of this study were to assess (a) the thawing times and (b) in vitro haemostatic quality of thawed plasma using Barkey Plasmatherm V (PTV) at 37 and 45°C versus Barkey Plasmatherm Classic (PTC) at 37 and 45°C, Sarstedt Sahara-III Maxitherm (SS-III) at 37°C and Helmer Scientific Thermogenesis Thermoline (TT) at 37°C. Haemostatic quality was assessed using LG-Octaplas at three different time points: baseline (5 min), 24 and 120 h after thawing. RESULTS: The thawing time (SD) of 2 and 4 units was significantly different between different thawers. PTV at 45°C was the fastest method for both 2 and 4 units (7.06 min [0.68], 9.6 min [0.87], respectively). SS-III at 37°C being the slowest method (24.69 min [2.09] and 27.18 min [4.4], respectively) (p = < 0.05). Baseline measurements for all assays showed no significant difference in the prothrombin time, fibrinogen, FII, FV, protein C activity or free protein S antigen between all methods tested. However, at baseline PTV (both 37°C and 45°C) had significantly higher levels of FVII, FVIII and FXI and shortened activated partial thromboplastin time. DISCUSSION: PTV was the quickest method at thawing plasma at both 37 and at 45°C. The haemostatic quality of plasma thawed at 45 versus 37°C was not impaired. Thawing frozen plasma at 45°C should be considered.

A systematic review of whether Health Impact Assessment frameworks support best practice principles.

OBJECTIVES: Health Impact Assessment (HIA) is an evidence-based approach to assess the likely public health impacts of a policy or plan in any sector. Several HIA frameworks are available to guide practitioners doing a HIA. This systematic review sought to determine whether these support practitioners to meet best practice principles defined by the International Association for Impact Assessment. STUDY DESIGN: This was a systematic review. METHODS: Three complementary search strategies were used to identify frameworks in June 2022. We used three databases to find completed HIAs published in the last five years and hand-searched their reference lists for frameworks. We also searched 23 HIA repositories using Google's Advanced function and contacted HIA practitioners via two international mailing lists. We used a bespoke quality appraisal tool to assess frameworks against the principles. RESULTS: The search identified 24 HIA frameworks. None of the frameworks achieved a 'good' rating for all best practice principles. Many identified the principles but did not provide guidance on how to meet them at all HIA steps. The highest number of frameworks were rated 'good' for ethical use of evidence and comprehensive approach to health (n = 15). Eight frameworks were rated as 'good' for participation, and two for equity. The highest number of frameworks rated 'poor' for sustainability (n = 11). CONCLUSIONS: There is marked variation in the degree to which HIA frameworks support the best practice principles. HIA practitioners could select elements from different frameworks for practical guidance to meet all the best practice principles.

Advancing the social return on investment framework to capture the social value of public health interventions: semistructured interviews and a review of scoping reviews.

OBJECTIVES: Investment in public health has far-reaching impacts, not only on physical health but also on communities, economies and the environment. There is increasing demand to account for the wider impact of public health and the social value that can be created, which can be captured through the use of the social return on investment (SROI) framework. This study aims to explore the application of SROI and identify areas of advancement for its use in public health. STUDY DESIGN AND METHODS: Publically available SROI studies of public health interventions previously identified through published systematic scoping reviews were examined through a methodological lens. This was complemented by semistructured interviews with key public health academic experts with experience in the field of SROI. The results were thematically analysed and triangulated. RESULTS: In total, 53 studies and nine interviews were included in the analysis. All interviewees agreed that SROI is a suitable framework to demonstrate the social value of public health interventions. Developmental aspects were also identified through the analysis. This included a more systematic use of SROI principles and methodological developments. Lastly, it was identified that further advancements were needed to promote awareness of SROI and how it can be used to generate investment. CONCLUSION: By identifying key areas for advancement, the results from this study can be used to further refine the SROI framework for use within the speciality to promote investment in services and interventions that demonstrate maximum value to people, communities, economies and the environment.

Harnessing the potential of data-driven strategies to optimise transfusion practice.

No one doubts the significant variation in the practice of transfusion medicine. Common examples are the variability in transfusion thresholds and the use of tranexamic acid for surgery with likely high blood loss despite evidence-based standards. There is a long history of applying different strategies to address this variation, including education, clinical guidelines, audit and feedback, but the effectiveness and cost-effectiveness of these initiatives remains unclear. Advances in computerised decision support systems and the application of novel electronic capabilities offer alternative approaches to improving transfusion practice. In England, the National Institute for Health and Care Research funded a Blood and Transplant Research Unit (BTRU) programme focussing on 'A data-enabled programme of research to improve transfusion practices'. The overarching aim of the BTRU is to accelerate the development of data-driven methods to optimise the use of blood and transfusion alternatives, and to integrate them within routine practice to improve patient outcomes. One particular area of focus is implementation science to address variation in practice.

RENEB Inter-Laboratory Comparison 2021: Inter-Assay Comparison of Eight Dosimetry Assays.

Tools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results. In the current RENEB inter-laboratory comparison, the performance quality of established cytogenetic assays [dicentric chromosome assay (DCA), cytokinesis-block micronucleus assay (CBMN), stable chromosomal translocation assay (FISH) and premature chromosome condensation assay (PCC)] was tested in comparison to molecular biological assays [gamma-H2AX foci (gH2AX), gene expression (GE)] and physical dosimetry-based assays [electron paramagnetic resonance (EPR), optically or thermally stimulated luminescence (LUM)]. Three blinded coded samples (e.g., blood, enamel or mobiles) were exposed to 0, 1.2 or 3.5 Gy X-ray reference doses (240 kVp, 1 Gy/min). These doses roughly correspond to clinically relevant groups of unexposed to low exposed (0-1 Gy), moderately exposed (1-2 Gy, no severe acute health effects expected) and highly exposed individuals (>2 Gy, requiring early intensive medical care). In the frame of the current RENEB inter-laboratory comparison, samples were sent to 86 specialized teams in 46 organizations from 27 nations for dose estimation and identification of three clinically relevant groups. The time for sending early crude reports and more precise reports was documented for each laboratory and assay where possible. The quality of dose estimates was analyzed with three different levels of granularity, 1. by calculating the frequency of correctly reported clinically relevant dose categories, 2. by determining the number of dose estimates within the uncertainty intervals recommended for triage dosimetry (±0.5 Gy or ±1.0 Gy for doses <2.5 Gy or >2.5 Gy), and 3. by calculating the absolute difference (AD) of estimated doses relative to the reference doses. In total, 554 dose estimates were submitted within the 6-week period given before the exercise was closed. For samples processed with the highest priority, earliest dose estimates/categories were reported within 5-10 h of receipt for GE, gH2AX, LUM, EPR, 2-3 days for DCA, CBMN and within 6-7 days for the FISH assay. For the unirradiated control sample, the categorization in the correct clinically relevant group (0-1 Gy) as well as the allocation to the triage uncertainty interval was, with the exception of a few outliers, successfully performed for all assays. For the 3.5 Gy sample the percentage of correct classifications to the clinically relevant group (≥2 Gy) was between 89-100% for all assays, with the exception of gH2AX. For the 1.2 Gy sample, an exact allocation to the clinically relevant group was more difficult and 0-50% or 0-48% of the estimates were wrongly classified into the lowest or highest dose categories, respectively. For the irradiated samples, the correct allocation to the triage uncertainty intervals varied considerably between assays for the 1.2 Gy (29-76%) and 3.5 Gy (17-100%) samples. While a systematic shift towards higher doses was observed for the cytogenetic-based assays, extreme outliers exceeding the reference doses 2-6 fold were observed for EPR, FISH and GE assays. These outliers were related to a particular material examined (tooth enamel for EPR assay, reported as kerma in enamel, but when converted into the proper quantity, i.e. to kerma in air, expected dose estimates could be recalculated in most cases), the level of experience of the teams (FISH) and methodological uncertainties (GE). This was the first RENEB ILC where everything, from blood sampling to irradiation and shipment of the samples, was organized and realized at the same institution, for several biological and physical retrospective dosimetry assays. Almost all assays appeared comparably applicable for the identification of unexposed and highly exposed individuals and the allocation of medical relevant groups, with the latter requiring medical support for the acute radiation scenario simulated in this exercise. However, extreme outliers or a systematic shift of dose estimates have been observed for some assays. Possible reasons will be discussed in the assay specific papers of this special issue. In summary, this ILC clearly demonstrates the need to conduct regular exercises to identify research needs, but also to identify technical problems and to optimize the design of future ILCs.

RENEB Inter-Laboratory Comparison 2021: The Dicentric Chromosome Assay.

After large-scale radiation accidents where many individuals are suspected to be exposed to ionizing radiation, biological and physical retrospective dosimetry assays are important tools to aid clinical decision making by categorizing individuals into unexposed/minimally, moderately or highly exposed groups. Quality-controlled inter-laboratory comparisons of simulated accident scenarios are regularly performed in the frame of the European legal association RENEB (Running the European Network of Biological and Physical retrospective Dosimetry) to optimize international networking and emergency readiness in case of large-scale radiation events. In total 33 laboratories from 22 countries around the world participated in the current RENEB inter-laboratory comparison 2021 for the dicentric chromosome assay. Blood was irradiated in vitro with X rays (240 kVp, 13 mA, ∼75 keV, 1 Gy/min) to simulate an acute, homogeneous whole-body exposure. Three blood samples (no. 1: 0 Gy, no. 2: 1.2 Gy, no. 3: 3.5 Gy) were sent to each participant and the task was to culture samples, to prepare slides and to assess radiation doses based on the observed dicentric yields from 50 manually or 150 semi-automatically scored metaphases (triage mode scoring). Approximately two-thirds of the participants applied calibration curves from irradiations with γ rays and about 1/3 from irradiations with X rays with varying energies. The categorization of the samples in clinically relevant groups corresponding to individuals that were unexposed/minimally (0-1 Gy), moderately (1-2 Gy) or highly exposed (>2 Gy) was successfully performed by all participants for sample no. 1 and no. 3 and by ≥74% for sample no. 2. However, while most participants estimated a dose of exactly 0 Gy for the sham-irradiated sample, the precise dose estimates of the samples irradiated with doses >0 Gy were systematically higher than the corresponding reference doses and showed a median deviation of 0.5 Gy (sample no. 2) and 0.95 Gy (sample no. 3) for manual scoring. By converting doses estimated based on γ-ray calibration curves to X-ray doses of a comparable mean photon energy as used in this exercise, the median deviation decreased to 0.27 Gy (sample no. 2) and 0.6 Gy (sample no. 3). The main aim of biological dosimetry in the case of a large-scale event is the categorization of individuals into clinically relevant groups, to aid clinical decision making. This task was successfully performed by all participants for the 0 Gy and 3.5 Gy samples and by 74% (manual scoring) and 80% (semiautomatic scoring) for the 1.2 Gy sample. Due to the accuracy of the dicentric chromosome assay and the high number of participating laboratories, a systematic shift of the dose estimates could be revealed. Differences in radiation quality (X ray vs. γ ray) between the test samples and the applied dose effect curves can partly explain the systematic shift. There might be several additional reasons for the observed bias (e.g., donor effects, transport, experimental conditions or the irradiation setup) and the analysis of these reasons provides great opportunities for future research. The participation of laboratories from countries around the world gave the opportunity to compare the results on an international level.

Is YouTube™ a good source of information for patients to understand laparoscopic fundoplication?

INTRODUCTION: Gastro-oesophageal reflux disease affects 10-20% of the population, and laparoscopic fundoplication is one management option. As the most frequently accessed video-sharing website, YouTube has become a popular source of information for patients. This study conducted a cross-sectional analysis of the quality and demographics of patient education videos available on YouTube for laparoscopic fundoplication. METHODS: Three searches were performed on YouTube using the phrases 'laparoscopic fundoplication', 'heartburn surgery' and 'reflux operation'. The Health on The Net (HON) code, DISCERN and Journal of the American Medical Association (JAMA) systems were used to score the first 75 results from each query. Information about each video was collected, including number of views, time since posting, number of comments and the author of the video. Relationships between these variables and video quality were investigated. RESULTS: The median number of views was 3,793. The most common author category was videos produced by surgeons. Overall the quality was poor, mean HON score was 2.5/8, mean DISCERN score was 29.3/80 and mean JAMA score was 1.5/4. Surgeon-authored videos scored higher when scored using the HON and JAMA systems. Videos of longer duration scored higher using all three scoring systems. No other factors were found to be associated with video quality. CONCLUSION: The quality of information in YouTube videos on laparoscopic fundoplication is unreliable. Doctors should be aware of this and caution their patients of YouTube's limitations. Further research is needed to develop validated scoring systems for evaluating the quality of patient education videos.

Trade-offs between succulent and non-succulent epiphytes underlie variation in drought tolerance and avoidance.

Epiphyte communities comprise important components of many forest ecosystems in terms of biomass and diversity, but little is known regarding trade-offs that underlie diversity and structure in these communities or the impact that microclimate has on epiphyte trait allocation. We measured 22 functional traits in vascular epiphyte communities across six sites that span a microclimatic gradient in a tropical montane cloud forest region in Costa Rica. We quantified traits that relate to carbon and nitrogen allocation, gas exchange, water storage, and drought tolerance. Functional diversity was high in all but the lowest elevation site where drought likely limits the success of certain species with particular trait combinations. For most traits, variation was explained by relationships with other traits, rather than differences in microclimate across sites. Although there were significant differences in microclimate, epiphyte abundance, and diversity, we found substantial overlap in multivariate trait space across five of the sites. We found significant correlations between functional traits, many of which related to water storage (leaf water content, leaf thickness, hydrenchymal thickness), drought tolerance (turgor loss point), and carbon allocation (specific leaf area, leaf dry matter content). This suite of trait correlations suggests that the epiphyte community has evolved functional strategies along with a drought avoidance versus drought tolerance continuum where leaf succulence emerged as a pivotal overall trait.

A pooled analysis of randomized, controlled, phase 3 trials investigating the efficacy and safety of a novel, fixed dose calcipotriene and betamethasone dipropionate cream for the topical treatment of plaque psoriasis.

BACKGROUND: Plaque psoriasis is a common, chronic and relapsing inflammatory skin disease clinically characterized by erythema and scaling desquamation. As over 90% of psoriasis patients benefit from topical therapies, local treatments continue to play an eminent role in management strategies. One such topical treatment is the fixed dose combination of calcipotriol (CAL) and betamethasone dipropionate (BDP). OBJECTIVES: Pooled analysis of two different phase 3 clinical trails to compare superiority regarding efficacy, safety and quality of life (QoL) between CAL/BDP PAD-cream and CAL/BDP TS. METHODS: The data from two phase 3, multicentre, randomized, investigator-blind, active and vehicle-controlled trials enrolling patients with psoriasis were pooled and analysed. Investigational products included a CAL/BDP cream based on PAD™ Technology (PAD-cream) designed for high skin penetration and increased patient preference, an active control (marketed CAL/BDP topical suspension/gel, in the following abbreviated as CAL/BDP TS) and cream vehicle, which were applied once daily for 8 weeks. RESULTS: Efficacy and safety of the novel CAL/BDP PAD-cream formulation for the topical treatment of psoriasis demonstrated superiority for all efficacy end points after 8 weeks of treatment. PGA treatment success for CAL/BDP PAD-cream (43.2%) was greater than CAL/BDP TS (31.9%; P < 0.0001), the mean per cent reduction in mPASI for CAL/BDP PAD-cream was 64.6% compared to 56.4% for CAL/BDP TS (P < 0.0001) and DLQI 0/1 was obtained by 43.8% in the CAL/BDP PAD-cream group versus 34.2% in the CAL/BDP TS group (P = 0.0005). There was no adverse drug reaction reported with a frequency of >1%, associated with the CAL/BDP PAD-cream. CONCLUSIONS: The novel fixed dose combination CAL/BDP PAD-cream offers greater efficacy, superior patient QoL and equivalent favourable safety for the topical treatment of psoriasis, in comparison to the currently available topical suspension/gel.

Early cryoprecipitate transfusion versus standard care in severe postpartum haemorrhage: a pilot cluster-randomised trial.

There is a lack of evidence evaluating cryoprecipitate transfusion in severe postpartum haemorrhage. We performed a pilot cluster-randomised controlled trial to evaluate the feasibility of a trial on early cryoprecipitate delivery in severe postpartum haemorrhage. Pregnant women (>24 weeks gestation), actively bleeding within 24 h of delivery and who required at least one unit of red blood cells were eligible. Women declining transfusion in advance or with inherited clotting deficiencies were not eligible. Four UK hospitals were randomly allocated to deliver either the intervention (administration of two pools of cryoprecipitate within 90 min of first red blood cell unit requested plus standard care), or the control group treatment (standard care, where cryoprecipitate is administered later or not at all). The primary outcome was the proportion of women who received early cryoprecipitate (intervention) vs. standard care (control). Secondary outcomes included consent rates, acceptability of the intervention, safety outcomes and preliminary clinical outcome data to inform a definitive trial. Between March 2019 and January 2020, 199 participants were recruited; 19 refused consent, leaving 180 for analysis (110 in the intervention and 70 in the control group). Adherence to assigned treatment was 32% (95%CI 23-41%) in the intervention group vs. 81% (95%CI 70-90%) in the control group. The proportion of women receiving cryoprecipitate at any time-point was higher in the intervention (60%) vs. control (31%) groups; the former had fewer red blood cell transfusions at 24 h (mean difference -0.6 units, 95%CI -1.2 to 0); overall surgical procedures (odds ratio 0.6, 95%CI 0.3-1.1); and intensive care admissions (odds ratio 0.4, 95%CI 0.1-1.1). There was no increase in serious adverse or thrombotic events in the intervention group. Staff interviews showed that lack of awareness and uncertainty about study responsibilities contributed to lower adherence in the intervention group. We conclude that a full-scale trial may be feasible, provided that protocol revisions are put in place to establish clear lines of communication for ordering early cryoprecipitate in order to improve adherence. Preliminary clinical outcomes associated with cryoprecipitate administration are encouraging and merit further investigation.

Prefrontal transcranial magnetic stimulation for depression in US military veterans - A naturalistic cohort study in the veterans health administration.

BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) is an evidence-based treatment for pharmacoresistant major depressive disorder (MDD), however, the evidence in veterans has been mixed. To this end, VA implemented a nationwide TMS program that included evaluating clinical outcomes within a naturalistic design. TMS was hypothesized to be safe and provide clinically meaningful reductions in MDD and posttraumatic stress disorder (PTSD) symptoms. METHODS: Inclusion criteria were MDD diagnosis and standard clinical TMS eligibility. Of the 770 patients enrolled between October 2017 and March 2020, 68.4% (n = 521) met threshold-level PTSD symptom criteria. Treatments generally used standard parameters (e.g., left dorsolateral prefrontal cortex, 120% motor threshold, 10 Hz, 3000 pulses/treatment). Adequate dose was operationally defined as 30 sessions. MDD and PTSD symptoms were measured using the 9-item patient health questionnaire (PHQ-9) and PTSD checklist for DSM-5 (PCL-5), respectively. RESULTS: Of the 770 who received at least one session, TMS was associated with clinically meaningful (Cohen's d>1.0) and statistically significant (all p<.001) reductions in MDD and PTSD. Of the 340 veterans who received an adequate dose, MDD response and remission rates were 41.4% and 20%, respectively. In veterans with comorbid PTSD, 65.3% demonstrated clinically meaningful reduction and 46.1% no longer met PTSD threshold criteria after TMS. Side effects were consistent with the known safety profile of TMS. LIMITATIONS: Include those inherent to retrospective observational cohort study in Veterans. CONCLUSIONS: These multisite, large-scale data supports the effectiveness and safety of TMS for veterans with MDD and PTSD using standard clinical approaches.

Analyzing long-term water quality of lakes in Rhode Island and the northeastern United States with an anomaly approach.

Addressing anthropogenic impacts on aquatic ecosystems is a focus of lake management. Controlling phosphorus and nitrogen can mitigate these impacts, but determining management effectiveness requires long-term datasets. Recent analysis of the LAke multi-scaled GeOSpatial and temporal database for the Northeast (LAGOS-NE) United States found stable water quality in the northeastern and midwestern United States; however, sub-regional trends may be obscured. We used the University of Rhode Island's Watershed Watch Volunteer Monitoring Program (URIWW) dataset to determine if there were sub-regional (i.e., 3000 km2) water quality trends. URIWW has collected water quality data on Rhode Island lakes and reservoirs for over 25 yr. The LAGOS-NE and URIWW datasets allowed for comparison of water quality trends at regional and sub-regional scales, respectively. We assessed regional (LAGOS-NE) and sub-regional (URIWW) trends with yearly median anomalies calculated on a per-station basis. Sub-regionally, temperature and chlorophyll a increased from 1993 to 2016. Total nitrogen, total phosphorus, and the nitrogen:phosphorus ratio (N:P) were stable. At the regional scale, the LAGOS-NE dataset showed similar trends to prior studies of the LAGOS-NE with chlorophyll a, total nitrogen, and N:P all stable over time. Total phosphorus did show a very slight increase. In short, algal biomass, as measured by chlorophyll a in Rhode Island lakes and reservoirs increased, despite stability in total nitrogen, total phosphorus, and the nitrogen to phosphorus ratio. Additionally, we demonstrated both the value of long-term monitoring programs, like URIWW, for identifying trends in environmental condition, and the utility of site-specific anomalies for analyzing for long-term water quality trends.

First insight into plastics ingestion by fish in the Gulf of California, Mexico.

Plastic particle occurrence in the digestive tracts of fishes from a tropical estuarine system in the Gulf of California was investigated. A total of 1095 fish were analysed, representing 15 species. In total 1384 particles of plastic debris were recovered from the gastrointestinal tracts of 552 specimens belonging to 13 species, and all consisted of threads, the majority of which were small microplastics (0.23 to 1.89), followed by large microplastics (2.07 to 4.49), and few mesoplastics (5.4 to 19.86). Plastic particles were identified using ATR-FTIR spectroscopy. The mean frequency of occurrence of plastics in the gastrointestinal tracts of fishes from this system was 50.5%, which is higher than frequencies reported in similar systems in other areas. The polymers identified by ATR-FTIR were polyamide (51.2%), polyethylene (36.6%), polypropylene (7.3%), and polyacrylic (4.9%). These results show the first evidence of plastic contamination for estuarine biota in the Gulf of California.

A Feeling for the Human Subject: Margaret Lasker and the Genetic Puzzle of Pentosuria.

In 1933 Margaret Lasker, a biochemist who worked at the labs of Montefiore Hospital in New York, developed an accurate method for the differentiation between pentosuria and diabetes. Research into pentosuria, and mostly its genetic aspects, became Lasker's lifelong passion. Since research was not part of her job description, she conducted the chief part of her study in her home kitchen. Lasker's extensive and personal correspondence with her patients and their families may be the secret key for her success in maintaining a prolonged research career against all odds. Laker's last article was published in 1955 in Human Biology, presenting data on 72 cases of pentosuria, which occurs almost exclusively in Ashkenazi Jews. More than half a century later, and long after Lasker was gone, her well kept data and family records allowed the discovery of two mutations in the DCXR gene, by Mary-Claire King and her team.

Phenyl bioisosteres in medicinal chemistry: discovery of novel γ-secretase modulators as a potential treatment for Alzheimer's disease.

Phenyl rings are one of the most prevalent structural moieties in active pharmaceutical ingredients, even if they often contribute to poor physico-chemical properties. Herein, we propose the use of a bridged piperidine (BP) moiety as a phenyl bioisostere, which could also be seen as a superior phenyl alternative as it led to strongly improved drug like properties, in terms of solubility and lipophilicity. Additionally, this BP moiety compares favorably to the recently reported saturated phenyl bioisosteres. We applied this concept to our γ-secretase modulator (GSM) project for the potential treatment of Alzheimer's disease delivering clinical candidates.

Multiple model triangulation to identify factors associated with lameness in British sheep flocks.

Identification of factors associated with an outcome can be challenging when the number of explanatory variables is large in relation to the number of observations. Multiple model triangulation, where results from several model types are combined, improves the likelihood of identifying true predictor variables. The aim of this study was to use triangulation to identify covariates likely to be truly associated with the prevalence of lameness in sheep flocks in Great Britain. Data were collected using a questionnaire sent to 3200 sheep farmers in Great Britain in 2018. The useable response rate was 14.1 %. The geometric mean prevalence of lameness was 1.4 % (95 % CI 1.2-1.7) for ewes, and 0.6 % (95 % CI 0.5-0.9) for lambs, however, approximately 60 % flocks had >2% prevalence of lameness in ewes. Four model types were investigated, two generalised linear models (negative binomial and quasi-Poisson) built using stepwise selection, and two elastic net models (Poisson and Gaussian distributions) refined with selection stability estimation. Triangulated covariates were those selected in three or all four models - 10 for ewes and 12 for lambs. Higher prevalence of lameness in ewes was associated with 5-100% feet bleeding during routine foot trimming compared with not foot trimming, footbathing the flock to treat severe footrot (SFR) and always using formalin in footbaths, both compared with not footbathing, using FootVax™ for <1 year compared with not using FootVax™, and never quarantining new or returning sheep to the farm for >3 weeks compared with always. Lower prevalence of lameness in ewes was associated with vaccinating with FootVax™ for >5 years compared with not vaccinating, peat soil compared with no peat soil, and having no lame ewes to treat. Higher prevalence of lameness in lambs was associated with 5-100% feet bleeding during routine foot trimming, always foot trimming ewes with SFR, not knowingly selecting replacement ewes from ewes that were never lame compared with always, replacement sheep purchased and homebred compared with only homebred, treating lambs >3 days after recognition of lameness compared with 0-3 days and footbathing the flock to treat interdigital dermatitis compared with not footbathing at all. Lower prevalence of lameness in lambs was associated with peat soil, flocks in Scotland versus England, an altitude of >230-500 m compared with ≤230 m, never using antibiotic injection to treat lambs with SFR compared with always, and having no lame lambs to treat. We conclude triangulation identified reliable management practices for farmers to implement to minimise lameness in sheep.

Prothrombin complex concentrate vs. fresh frozen plasma in adult patients undergoing heart surgery - a pilot randomised controlled trial (PROPHESY trial).

There is equipoise regarding the use of prothrombin complex concentrate vs. fresh frozen plasma in bleeding patients undergoing cardiac surgery. We performed a pilot randomised controlled trial to determine the recruitment rate for a large trial, comparing the impact of prothrombin complex concentrate vs. fresh frozen plasma on haemostasis (1 h and 24 h post-intervention), and assessing safety. Adult patients who developed bleeding within 24 h of cardiac surgery that required coagulation factor replacement were randomly allocated to receive prothrombin complex concentrate (15 IU.kg-1 based on factor IX) or fresh frozen plasma (15 ml.kg-1 ). If bleeding continued after the first administration of prothrombin complex concentrate or fresh frozen plasma administration, standard care was administered. From February 2019 to October 2019, 180 patients were screened, of which 134 (74.4% (95%CI 67-81%)) consented, 59 bled excessively and 50 were randomly allocated; 25 in each arm, recruitment rate 35% (95%CI 27-44%). There were 23 trial protocol deviations, 137 adverse events (75 prothrombin complex concentrate vs. 62 fresh frozen plasma) and 18 serious adverse events (5 prothrombin complex concentrate vs. 13 fresh frozen plasma). There was no increase in thromboembolic events with prothrombin complex concentrate. No patient withdrew from the study, four were lost to follow-up and two died. At 1 h after administration of the intervention there was a significant increase in fibrinogen, Factor V, Factor XII, Factor XIII, α2 -antiplasmin and antithrombin levels in the fresh frozen plasma arm, while Factor II and Factor X were significantly higher in the prothrombin complex concentrate group. At 24 h, there were no significant differences in clotting factor levels. We conclude that recruitment to a larger study is feasible. Haemostatic tests have provided useful insight into the haemostatic changes following prothrombin complex concentrate or fresh frozen plasma administration. A definitive trial is needed to ascertain the benefits and safety for each.

Comparable efficacy and safety of brodalumab in obese and nonobese patients with psoriasis: analysis of two randomized controlled trials.

BACKGROUND: Obesity is associated with psoriasis and negatively affects response to therapy. OBJECTIVES: To evaluate the efficacy and safety of brodalumab in nonobese vs. obese patients with psoriasis. METHODS: This is a post hoc analysis of the prospective, phase III, multicentre, randomized, placebo- and active-comparator-controlled AMAGINE-2 and AMAGINE-3 trials, in which patients were randomized to treatment with brodalumab 210 mg every 2 weeks, ustekinumab or placebo for a 12-week induction phase. At week 12, patients who received brodalumab 210 mg every 2 weeks continued brodalumab, those treated with ustekinumab continued ustekinumab, and those who received placebo switched to brodalumab 210 mg every 2 weeks. Patients were categorized by body mass index (BMI) category (< 30 or ≥ 30 kg m-2 ) and efficacy was evaluated using the physician-rated Psoriasis Area and Severity Index and static Physician's Global Assessment instruments. RESULTS: In total, 281 of 687 patients (40·9%) were obese. Skin clearance was comparable across BMI subgroups in brodalumab-treated patients. Psoriasis Area and Severity Index 100% improvement rates in nonobese and obese patients at week 12 were 54·1% and 49·5%, respectively, and at week 52 they were 72·6% and 64·8%, respectively. Week 12 ustekinumab responses were lower than brodalumab responses and were 6-17% lower in obese than in nonobese patients. No appreciable differences in overall safety were observed between nonobese and obese patients. CONCLUSIONS: The efficacy and safety of brodalumab did not differ between patients with moderate-to-severe psoriasis who had a BMI < 30 kg m-2 or a BMI ≥ 30 kg m-2 .

The large-scale capture of eastern grey kangaroos (Macropus giganteus) and red kangaroos (Osphranter rufus) and its application to a population management project.

OBJECTIVE: A large-scale capture method was developed to enable sterilisation of a macropod population in western Sydney from 2005 to 2018. METHODS: Until March 2007, free ranging eastern grey kangaroos and red kangaroos were herded into purpose-built 15 m diameter capture yards (CYs) for darting with a projectile syringe. From March 2007 onwards, animals were free-range darted in large areas without herding. Kangaroos were darted with 1.33-5.10 mg/kg tiletamine/zolazepam and 0.01-0.02 mg/kg medetomidine, ± 0.03 mg/kg acepromazine. Deaths were monitored. Population counts were performed annually. RESULTS: There were 5825 capture events involving 3963 kangaroos. Over 85% of all captures occurred from 2005 to 2008. Of all reported deaths (n = 523), 135 were attributed to ill health. Musculoskeletal injuries incurred during capture were the main project-related cause of death (n = 116). Post capture myopathy was uncommonly diagnosed following capture (n = 19). CONCLUSION: The herding and capture method enabled a large number of kangaroos to be mobilised and captured with low mortality rates, and the use of CYs resulted in fewer capture-related injuries and deaths than free-range capture. The drug doses and combinations used for darting were safe and effective, and the capture technique was successfully applied to a population management project.