Search

Experiments providing evidence for the importance of stimulus enhancement unconfounded by social facilitation and local enhancement in animals' food-finding behavior are described. This suggests that demonstrator-deposited scent cuses can facilitate discrimination via local enhancement or on the basis of their sensory properties alone.

Prostacyclin (PGI2) production was diminished when rat aortic rings were incubated with plasma from 5 of 6 patients with the sporadic form of haemolytic uraemic syndrome but was normal in the presence of plasma from 7 patients with the epidemic form of haemolytic uraemic syndrome or from patients with other renal diseases. The reduced PGI2 production was caused by an unstable inhibitor, extractable into polar lipid solvents, in sporadic haemolytic uraemic plasma. These results suggest that there may be at least 2 different pathogenetic mechanisms in epidemic and sporadic haemolytic uraemic syndrome and that the reduced PGI2 production observed in the sporadic type is due to an inhibitor of PGI2 production rather than a deficiency of stimulating factors. [ABSTRACT FROM AUTHOR]

An increasing number of people are taking anticoagulants for the prophylaxis of thromboembolic disease. This may cause problems when they attend hospital following trauma. Patients may also develop spontaneous bleeding that may have similar effects to bleeding after an injury. This article discusses the risks of bleeding (especially in head injury); the risks of stopping anticoagulation; how anticoagulation should be reversed and how anticoagulation should affect the approach to the head-injured patient. [ABSTRACT FROM AUTHOR]

Few studies have reported the real-world use of both romiplostim and eltrombopag in immune thrombocytopenia (ITP). TRAIT was a retrospective observational study aimed to evaluate the platelet responses and adverse effects associated with the use of these thrombopoietin receptor agonists (TPO-RAs) in adult patients with ITP in the United Kingdom. Of 267 patients (median age at diagnosis, 48 years) with ITP (primary ITP [n = 218], secondary ITP [n = 49]) included in the study, 112 (42%) received eltrombopag and 155 (58%) received romiplostim as the first prescribed TPO-RA. A platelet count ≥30 × 10 9 /L was achieved in 89% of patients with the first TPO-RA treatments, while 68% achieved a platelet count ≥100 × 10 9 /L. Treatment-free response (TFR; platelet count ≥30 × 10 9 /L, 3 months after discontinuing treatment) was achieved by 18% of the total patients. Overall, 61 patients (23%) switched TPO-RAs, most of whom achieved platelet counts ≥30 × 10 9 /L with the second TPO-RA (23/25 who switched from eltrombopag to romiplostim [92%]; 28/36 who switched from romiplostim to eltrombopag [78%]). TFR was associated with secondary ITP, early TPO-RA initiation after diagnosis, the presence of comorbidity and no prior splenectomy or treatment with steroids or mycophenolate mofetil. Both TPO-RAs had similar efficacy and safety profiles to those reported in clinical studies., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

There is approximately a 2% risk of clinically significant VTE following temporary lower limb immobilisation after injury with an ankle immobilising plaster cast or boot. There is evidence that thromboprophylaxis for lower limb immobilised patients reduces the risk of VTE by approximately 50% but there is no international consensus as to which patients should receive thromboprophylaxis. The Plymouth VTE Risk Score was developed to identify patients at particular risk of VTE, in order to offer chemical prophylaxis to reduce their VTE risk. The score showed high completion rates, reliability and consistency. Using the Plymouth VTE Risk Score Version 3 (2014), we found an incidence of clinical VTE of 0.36% with 37.6% of patients being advised to have thromboprophylaxis. This is a lower VTE incidence than in most other studies of this patient group, which is of the order of 2 to 3%. The optimal RAM to use in clinical practice is yet to be defined, further clinical research is needed to accurately stratify patient risk and to define optimal risk treatment levels. We suggest research should focus on comparative clinical studies of risk assessment models., Competing Interests: Declaration of Competing Interest Although none of the authors has received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this article, benefits have been or will be received but will be directed solely to a research fund, foundation, educational institution, or other non- profit organization with which one or more of the authors are associated. Printing of Plymouth VTE Risk Score sheets were supported by a medical and educational grant from Sanofi to University Hospitals Plymouth NHS Trust., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Background: Thromboprophylaxis has the potential to reduce venous thromboembolism (VTE) following lower limb immobilization resulting from injury., Objectives: We aimed to estimate the effectiveness of thromboprophylaxis, compare different agents, and identify any factors associated with effectiveness., Methods: We undertook a systematic review and network meta-analysis (NMA) of randomized trials reporting VTE or bleeding outcomes that compared thromboprophylactic agents with each other or to no pharmacological prophylaxis, for this indication. An NMA was undertaken for each outcome or agent used, and a series of study-level network meta-regressions examined whether population characteristics, type of injury, treatment of injury, or duration of thromboprophylaxis were associated with treatment effect., Results: Data from 6857 participants across 13 randomized trials showed that, compared with no treatment, low molecular weight heparin (LMWH) reduced the risk of any VTE (odds ratio [OR]: 0.52; 95% credible interval [CrI]: 0.37-0.71), clinically detected deep vein thrombosis (DVT) (OR: 0.39; 95% CrI: 0.12-0.94) and pulmonary embolism (PE) (OR: 0.16; 95% CrI: 0.01-0.74), whereas fondaparinux reduced the risk of any VTE (OR: 0.13; 95% CrI: 0.05-0.30) and clinically detected DVT (OR: 0.10; 95% CrI: 0.01-0.86), with inconclusive results for PE (OR: 0.40; 95% CrI: 0.01-7.53)., Conclusions: Thromboprophylaxis with either fondaparinux or LMWH appears to reduce the odds of both asymptomatic and clinically detected VTE in people with temporary lower limb immobilization following an injury. Treatment effects vary by outcome and are not always conclusive. We were unable to identify any treatment effect modifiers other than thromboprophylactic agent used., (© 2019 Crown copyright. Journal of Thrombosis and Haemostasis © 2019 International Society on Thrombosis and Haemostasis.)

Venous thromboembolic disease is a major global cause of morbidity and mortality. An estimated 10 million episodes are diagnosed yearly; over half of these episodes are provoked by hospital admission/procedures and result in significant loss of disability adjusted life years. Temporary lower limb immobilisation after injury is a significant contributor to the overall burden of venous thromboembolism (VTE). Existing evidence suggests that pharmacological prophylaxis could reduce overall VTE event rates in these patients, but the proportional reduction of symptomatic events remains unclear. Recent studies have used different pharmacological agents, dosing regimens and outcome measures. Consequently, there is wide variation in thromboprophylaxis strategies, and international guidelines continue to offer conflicting advice for clinicians. In this review, we provide a summary of recent evidence assessing both the clinical and cost effectiveness of thromboprophylaxis in patients with temporary immobilisation after injury. We also examine the evidence supporting stratified thromboprophylaxis and the validity of widely used risk assessment methods., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Thromboprophylaxis can reduce the risk of venous thromboembolism (VTE) during lower-limb immobilisation, but it is unclear whether or not this translates into meaningful health benefit, justifies the risk of bleeding or is cost-effective. Risk assessment models (RAMs) could select higher-risk individuals for thromboprophylaxis., Objectives: To determine the clinical effectiveness and cost-effectiveness of different strategies for providing thromboprophylaxis to people with lower-limb immobilisation caused by injury and to identify priorities for future research., Data Sources: Ten electronic databases and research registers (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects, the Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluation Database, Science Citation Index Expanded, ClinicalTrials.gov and the International Clinical Trials Registry Platform) were searched from inception to May 2017, and this was supplemented by hand-searching reference lists and contacting experts in the field., Review Methods: Systematic reviews were undertaken to determine the effectiveness of pharmacological thromboprophylaxis in lower-limb immobilisation and to identify any study of risk factors or RAMs for VTE in lower-limb immobilisation. Study quality was assessed using appropriate tools. A network meta-analysis was undertaken for each outcome in the effectiveness review and the results of risk-prediction studies were presented descriptively. A modified Delphi survey was undertaken to identify risk predictors supported by expert consensus. Decision-analytic modelling was used to estimate the incremental cost per quality-adjusted life-year (QALY) gained of different thromboprophylaxis strategies from the perspectives of the NHS and Personal Social Services., Results: Data from 6857 participants across 13 trials were included in the meta-analysis. Thromboprophylaxis with low-molecular-weight heparin reduced the risk of any VTE [odds ratio (OR) 0.52, 95% credible interval (CrI) 0.37 to 0.71], clinically detected deep-vein thrombosis (DVT) (OR 0.40, 95% CrI 0.12 to 0.99) and pulmonary embolism (PE) (OR 0.17, 95% CrI 0.01 to 0.88). Thromboprophylaxis with fondaparinux (Arixtra ® , Aspen Pharma Trading Ltd, Dublin, Ireland) reduced the risk of any VTE (OR 0.13, 95% CrI 0.05 to 0.30) and clinically detected DVT (OR 0.10, 95% CrI 0.01 to 0.94), but the effect on PE was inconclusive (OR 0.47, 95% CrI 0.01 to 9.54). Estimates of the risk of major bleeding with thromboprophylaxis were inconclusive owing to the small numbers of events. Fifteen studies of risk factors were identified, but only age (ORs 1.05 to 3.48), and injury type were consistently associated with VTE. Six studies of RAMs were identified, but only two reported prognostic accuracy data for VTE, based on small numbers of patients. Expert consensus was achieved for 13 risk predictors in lower-limb immobilisation due to injury. Modelling showed that thromboprophylaxis for all is effective (0.015 QALY gain, 95% CrI 0.004 to 0.029 QALYs) with a cost-effectiveness of £13,524 per QALY, compared with thromboprophylaxis for none. If risk-based strategies are included, it is potentially more cost-effective to limit thromboprophylaxis to patients with a Leiden thrombosis risk in plaster (cast) [L-TRiP(cast)] score of ≥ 9 (£20,000 per QALY threshold) or ≥ 8 (£30,000 per QALY threshold). An optimal threshold on the L-TRiP(cast) receiver operating characteristic curve would have sensitivity of 84-89% and specificity of 46-55%., Limitations: Estimates of RAM prognostic accuracy are based on weak evidence. People at risk of bleeding were excluded from trials and, by implication, from modelling., Conclusions: Thromboprophylaxis for lower-limb immobilisation due to injury is clinically effective and cost-effective compared with no thromboprophylaxis. Risk-based thromboprophylaxis is potentially optimal but the prognostic accuracy of existing RAMs is uncertain., Future Work: Research is required to determine whether or not an appropriate RAM can accurately select higher-risk patients for thromboprophylaxis., Study Registration: This study is registered as PROSPERO CRD42017058688., Funding: The National Institute for Health Research Health Technology Assessment programme., Competing Interests: Steve Goodacre is chairperson of the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme Clinical Evaluation and Trials Board and a member of the HTA Funding Boards Policy Group. Tim Nokes received personal fees from Bayer Pharmaceuticals (Bayer AG, Leverkusen, Germany), personal fees from the Bristol-Myers Squibb Company (New York City, NY, USA)–Pfizer Inc. (New York City, NY, USA) Alliance and personal fees from Daiichi Sankyo Company Ltd (Tokyo, Japan) outside the submitted work. Kerstin de Wit reports grants from Bayer Pharmaceuticals outside the submitted work.

A multicenter, retrospective, observational study of 4-factor prothrombin complex concentrate (PCC) and/or fresh frozen plasma (FFP) use within routine clinical care unrelated to vitamin K antagonists was conducted. The PCC was administered preprocedure for correction of coagulopathy (prophylactic cohort) and treatment of bleeding postsurgery (treatment cohort). Of the 445 patients included, 40 were in the prophylactic cohort (PCC alone [n = 16], PCC and FFP [n = 5], FFP alone [n = 19]) and 405 were in the treatment cohort (PCC alone [n = 228], PCC and FFP [n = 123], FFP alone [n = 54]). Cardiovascular surgery was the most common setting. PCC doses ranged between 500 and 5000 IU. Effectiveness (assessed retrospectively) was reported as effective in 93.0% in the PCC-only group (95% confidence interval, 89.1% to 95.9%), 78.9% (70.8% to 85.6%) with PCC and FFP, and 86.3% (76.2% to 93.2%) with FFP alone. In the treatment cohort, international normalized ratio was significantly reduced in all 3 groups. In patients who received PCC, the rate of thromboembolic events (1.9%) was below rates in the literature for similar procedures. PCCs offer a potential alternative to FFP in the management of perioperative bleeding unrelated to oral anticoagulant therapy.

The Department of Health has defined hospital acquired venous thromboembolism (VTE) as any VTE event occurring within 90 days of hospital admission or surgery. 1 Hospital acquired thrombosis (HAT) is common during and after hospital admission and is considered a major patient safety issue. Current NICE guideline (CG 92) 2010, recommends that medical patients assessed at risk of VTE should have pharmacological prophylaxis commenced as soon as possible after risk assessment has been completed and continued until the patient is no longer at increased risk of VTE. 2 This quality improvement project was carried out in the medical assessment unit in Derriford Hospital, Plymouth. We aimed to increase appropriate VTE pharmacological prophylaxis to 100% prescribed in 6 hours by the end of May 2016 using the Plan-Do-Study-Act (PDSA) methodology. The primary outcome measure was whether or not enoxaparin was given within 6 hours of admission. Analysis showed that a major contributing factor to the prolonged time interval was lack of awareness of the Trust VTE guidelines which had recently been updated in accordance with NICE recommendations. Baseline measurement demonstrated that 29% of patients had first dose of enoxaparin within the 6-hour target, with a mean delay of 12 hours 22 minutes. With implementation of an education programme and development of a local VTE prevention care pathway to raise awareness of the new guidelines, a significant improvement was achieved with 71% of patients meeting the 6-hour target in PDSA cycle 1 and 83% of patients in PDSA cycle 2. The average time interval also reduced to 5 hours 52 minutes in PDSA cycle 1 and 5 hours 7 minutes in PDSA cycle 2. In conclusion, through utilization of simple change methodology, enoxaparin prescribing practice significantly improved. Potentially this may reduce morbidity (and mortality) associated with HAT together with cost implications of its management.

Ventilation-perfusion (VQ) single-photon emission computed tomography (SPECT) comprised the administration of SmartVent (n=386) or Technegas (n=1564) and 200 MBq (99m)Tc-MAA. 1406 scans were normal, 462 showed PE, 61 showed a singular subsegmental mismatched defect, 21 scans were non-diagnostic. 26% of scans performed with Technegas showed PE, compared to 15% with SmartVent. VQ SPECT had a sensitivity of 95.7%, specificity 98.6%, positive predictive value 95.7%, negative predictive value 98.6%. A normal VQ SPECT scan implied a more than ten-fold lower cause-specific mortality (1 in 1406) than a scan showing PE (1 in 116). NPV of a negative D-dimer was 94.3%., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To determine the frequency of pulmonary involvement in patients with thrombotic thrombocytopenic purpura (TTP)., Methods: The experience of the Oklahoma TTP-HUS (hemolytic-uremic syndrome) Registry, a population-based cohort of consecutive patients without selection or referral bias, 1995-2012, was analyzed. Evidence for pulmonary involvement in patients with TTP was also documented with a systematic review of published reports., Results: Only one of 74 Registry patients with acquired severe ADAMTS13 deficiency (activity <10%) had clinically important pulmonary involvement (transient PaO2 , 42 mm Hg; arterial O2 saturation, 78%; normal chest X-ray). No clinically important pulmonary involvement occurred in the remaining 73 patients. The systematic review identified 144 articles with search terms for TTP and pulmonary involvement; seven, published 1978-2002, had evaluable individual patient data. Five articles described single patients; only one patient was documented to have severe acquired ADAMTS13 deficiency; in none of the five patients was pulmonary involvement clearly related to TTP. Two articles were case series of seven patients each; no patients had ADAMTS13 activity measured. Each of the 14 patients had potential etiologies other than TTP for pulmonary involvement., Conclusions: Only one of 74 patients in the Oklahoma Registry had clinically important pulmonary involvement. A systematic review of published reports documented no clear evidence for pulmonary involvement resulting from TTP. Clinically important pulmonary involvement may be rare in patients with TTP because (i) pulmonary microvasculature may be inherently resistant to the formation of platelet thrombi and (ii) pulmonary function can be maintained in spite of multiple microvascular thrombi., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in hospitalised patients. VTE prevention has been identified as a major health need internationally to improve patient safety. A National Institute for Health and Clinical Excellence (NICE) guideline was issued in February 2010. Its key priorities were to assess patients for risk of VTE on admission to hospital, assess patients for bleeding risk and evaluate the risks and benefits of prescribing VTE prophylaxis. The aim of this study was to evaluate the implementation of NICE guidance and its impact on patient safety., Methods: A before-after observational design was used to investigate changes in VTE risk assessment documentation and inappropriate prescribing of prophylaxis between the year prior to (2009) and the year following (2010) the implementation of NICE guidance, using data from a 3-week period during each year. A total of 408 patients were sampled in each year across four hospitals in the NHS South region., Results: Implementation strategies such as audit, education and training were used. The percentage of patients for whom a VTE risk assessment was documented increased from 51.5% (210/408) in 2009 to 79.2% (323/408) in 2010; difference 27.7% (95% CI: 21.4% to 33.9%; p < 0.001). There was little evidence of change in the percentage who were prescribed prophylaxis amongst patients without a risk assessment (71.7% (142/198) in 2009 and 68.2% (58/85) in 2010; difference -3.5% (95% CI: -15.2% to 8.2%; p =0.56) nor the percentage who were prescribed low molecular weight heparin amongst patients with a contraindication (14% (4/28) in 2009 and 15% (6/41) in 2010; RD = 0.3% (95% CI: -16.5% to 17.2%; p =0.97)., Conclusions: The documentation of risk assessment improved following the implementation of NICE guidance; it is questionable, however, whether this led to improved patient safety with respect to prescribing appropriate prophylaxis.

Venous thrombo-embolism (VTE) is increasingly recognized in paediatric practice. Few clinical trials have been performed in this area in children and management is largely extrapolated from adult practice where there is a considerable evidence base. This is likely to be unsatisfactory for a number of reasons. Firstly, there are significant differences in epidemiology and potential differences in the mechanisms for VTE in this age group. Secondly, many aspects of haemostasis are age-dependant, which has implications for the use of anticoagulants in the paediatric population. Thirdly, there are very limited data available on the safety and efficacy of anticoagulants to manage specific indications in paediatric practice, often with limited paediatric formulations available. In addition, children may survive for a prolonged period following these events so that long-term consequences may be highly significant in this age group. The aim of this guideline is to provide a rational basis for the investigation and management of children aged 1 month-16 years with VTE, including cerebral venous thrombosis (CVT). The guideline is targeted at healthcare professionals involved in the management of children and adolescents with VTE, particularly paediatric haematologists., (© 2011 Blackwell Publishing Ltd.)

The use of plasma D-dimer assay has been advocated for the exclusion of pulmonary embolism. We retrospectively looked at 840 patients in whom both ventilation-perfusion scan and D-dimer assay were performed within 48 h. The negative predictive value of a negative D-dimer assay was 96% for emergency admissions and 98% for inpatients. We present the cases of two patients with negative D-dimer assay results who had a high-probability lung scan, and we have found a further three patients with negative D-dimer assay results who had an intermediate-probability lung scan.

Venous thromboembolism (VTE) is a clinically important complication for both hospitalised and ambulatory cancer patients. In the current study, the frequency, demographics and risk (according to tumour site) of VTE were examined among patients seen at outpatient DVT (deep-vein thrombosis) clinics. Of 10,015 VTE cases, 1,361 were diagnosed with cancer, for an overall rate of cancer-associated VTE of 13.6% in this outpatient population. Patients with cancer-associated VTE were significantly older than cancer-free VTE cases (66.4 +/- 12.7 vs. 58.8 +/- 18.5 years; p<0.0001). The frequency of cancer-associated VTE peaked earlier among females than males, occurring in the sixth (137/639, 21.4% vs. 98/851, 11.3%; p<0.001) and seventh decades (213/980, 21.7% vs. 197/1096, 18%; p=0.036). VTE was described most frequently in common cancers - breast, prostate, colorectal and lung (56.1% of cases). The risk of VTE varied widely across 17 cancer types. Calculating odds ratios (OR) to assess the effect size of cancer type on VTE risk, the highest odds were observed for patients with pancreatic cancer (OR 9.65, 95% confidence interval [CI] (5.51-16.91). Tumours of the head and neck had higher odds than previously reported (OR 8.24, 95% CI 5.06-13.42). Reduced risk estimates were observed for skin cancers (melanoma and non-melanoma: OR 0.89, 95% CI 0.42-1.87; OR 0.74, 95% CI, 0.32-1.69, respectively). We conclude that outpatients have a similar rate of cancer-associated VTE as VTE patient populations previously reported, that cancer-associated VTE occurs in an older age group and earlier in females and that outpatients exhibit distinct tumour site-specific risk from that described among hospitalised cancer patients.