Albumin Versus Balanced Crystalloid for the Early Resuscitation of Sepsis: An Open Parallel-Group Randomized Feasibility Trial. The ABC-Sepsis Trial.

OBJECTIVES: International guidelines recommend IV crystalloid as the primary fluid for sepsis resuscitation, with 5% human albumin solution (HAS) as the second line. However, it is unclear which fluid has superior clinical effectiveness. We conducted a trial to assess the feasibility of delivering a randomized controlled trial comparing balanced crystalloid against 5% HAS as sole early resuscitation fluid in patients with sepsis presenting to hospital. DESIGN: Multicenter, open, parallel-group randomized feasibility trial. SETTING: Emergency departments (EDs) in 15 U.K. National Health Service (NHS) hospitals. PATIENTS: Adult patients with sepsis and a National Early Warning Score 2 greater than or equal to five requiring IV fluids withing one hour of randomization. INTERVENTIONS: IV fluid resuscitation with balanced crystalloid or 5% HAS for the first 6 hours following randomization. MEASUREMENTS AND MAIN RESULTS: Primary feasibility outcomes were recruitment rate and 30-day mortality. We successfully recruited 301 participants over 12 months. Mean (sd) age was 69 years (± 16 yr), and 151 (50%) were male. From 1303 participants screened; 502 participants were potentially eligible and 300 randomized to receive trial intervention with greater than 95% of participants receiving the intervention. The median number of participants per site was 19 (range, 1-63). Thirty-day mortality was 17.9% (n = 53). Thirty-one participants died (21.1%) within 30 days in the 5% HAS arm, compared with 22 participants (14.8%) in the crystalloid arm (adjusted odds ratio, 1.50; 95% CIs, 0.84-2.83). CONCLUSIONS: Our results suggest it is feasible to recruit critically ill patients to a fluid resuscitation trial in U.K. EDs using 5% HAS as a primary resuscitation fluid. There was lower mortality in the balanced crystalloid arm. Given these findings, a definitive trial is likely to be deliverable, but the point estimates suggest such a trial would be unlikely to demonstrate a significant benefit from using 5% HAS as a primary resuscitation fluid in sepsis.

Eccentric Exercise-Induced Muscle Damage Reduces Gross Efficiency.

INTRODUCTION: The effect of eccentric exercise-induced muscle damage (EIMD) on cycling efficiency is unknown. The aim of the present study was to assess the effect of EIMD on gross and delta efficiency and the cardiopulmonary responses to cycle ergometry. METHODS: Twenty-one recreational athletes performed cycling at 70%, 90% and 110% of the gas exchange threshold (GET) under control conditions (Control) and 24 h following an eccentric damaging protocol (Damage). Knee extensor isometric maximal voluntary contraction (MVC), potentiated twitch (Qtw,pot) and voluntary activation (VA) were assessed before Control and Damage. Gross and delta efficiency were assessed using indirect calorimetry, and cardiopulmonary responses were measured at each power output. Electromyography root-mean-square (EMGRMS) during cycling was also determined. RESULTS: MVC was 25 ± 18% lower for Damage than Control (p < 0.001). Gross efficiency was lower for Damage than Control (p < 0.001) by 0.55 ± 0.79%, 0.59 ± 0.73% and 0.60 ± 0.87% for 70%, 90% and 110% GET, respectively. Delta efficiency was unchanged between conditions (p = 0.513). Concurrently, cycling EMGRMS was higher for Damage than Control (p = 0.004). An intensity-dependent increase in breath frequency and V̇E/V̇CO2 was found, which were higher for Damage only at 110% GET (p ≤ 0.019). CONCLUSIONS: Thus, gross efficiency is reduced following EIMD. The concurrently higher EMGRMS suggests that increases in muscle activation in the presence of EIMD might have contributed to reduced gross efficiency. The lack of change in delta efficiency might relate to its poor reliability hindering the ability to detect change. The findings also show that EIMD-associated hyperventilation is dependent on exercise intensity, which might relate to increases in central command with EIMD.

The role of health policy in the prevention of venous thromboembolism in the UK National Health Service-Learning from the past, looking to the future.

Venous thromboembolism is the third most common cause of cardiovascular death globally and many diagnoses are preventable. The UK NHS has led international efforts to reduce VTE, particularly hospital-associated VTE, through coordinated national policy action and world-leading research. Despite this, VTE remains an important cause of morbidity and mortality in the UK, as underlined by the recent COVID-19 pandemic. Future reductions in VTE incidence/deaths will require progress on several fronts: a better understanding of case mix; revisiting VTE risk assessment, focussing on thromboprophylaxis failure and improving awareness of VTE amongst clinicians and the public. Changes to healthcare delivery, with care increasingly delivered outside of hospital, alongside changing disease patterns, including the rise in obesity, have huge implications for VTE and will dramatically alter prevention. The UK, with its nationalised healthcare model and long history of policy action on VTE, provides a unique lens through which to study past successes and future priorities for VTE prevention.

Evaluation of venous thromboembolism risk assessment models for hospital inpatients: the VTEAM evidence synthesis.

Background: Pharmacological prophylaxis during hospital admission can reduce the risk of acquired blood clots (venous thromboembolism) but may cause complications, such as bleeding. Using a risk assessment model to predict the risk of blood clots could facilitate selection of patients for prophylaxis and optimise the balance of benefits, risks and costs. Objectives: We aimed to identify validated risk assessment models and estimate their prognostic accuracy, evaluate the cost-effectiveness of different strategies for selecting hospitalised patients for prophylaxis, assess the feasibility of using efficient research methods and estimate key parameters for future research. Design: We undertook a systematic review, decision-analytic modelling and observational cohort study conducted in accordance with Enhancing the QUAlity and Transparency Of health Research (EQUATOR) guidelines. Setting: NHS hospitals, with primary data collection at four sites. Participants: Medical and surgical hospital inpatients, excluding paediatric, critical care and pregnancy-related admissions. Interventions: Prophylaxis for all patients, none and according to selected risk assessment models. Main outcome measures: Model accuracy for predicting blood clots, lifetime costs and quality-adjusted life-years associated with alternative strategies, accuracy of efficient methods for identifying key outcomes and proportion of inpatients recommended prophylaxis using different models. Results: We identified 24 validated risk assessment models, but low-quality heterogeneous data suggested weak accuracy for prediction of blood clots and generally high risk of bias in all studies. Decision-analytic modelling showed that pharmacological prophylaxis for all eligible is generally more cost-effective than model-based strategies for both medical and surgical inpatients, when valuing a quality-adjusted life-year at £20,000. The findings were more sensitive to uncertainties in the surgical population; strategies using risk assessment models were more cost-effective if the model was assumed to have a very high sensitivity, or the long-term risks of post-thrombotic complications were lower. Efficient methods using routine data did not accurately identify blood clots or bleeding events and several pre-specified feasibility criteria were not met. Theoretical prophylaxis rates across an inpatient cohort based on existing risk assessment models ranged from 13% to 91%. Limitations: Existing studies may underestimate the accuracy of risk assessment models, leading to underestimation of their cost-effectiveness. The cost-effectiveness findings do not apply to patients with an increased risk of bleeding. Mechanical thromboprophylaxis options were excluded from the modelling. Primary data collection was predominately retrospective, risking case ascertainment bias. Conclusions: Thromboprophylaxis for all patients appears to be generally more cost-effective than using a risk assessment model, in hospitalised patients at low risk of bleeding. To be cost-effective, any risk assessment model would need to be highly sensitive. Current evidence on risk assessment models is at high risk of bias and our findings should be interpreted in this context. We were unable to demonstrate the feasibility of using efficient methods to accurately detect relevant outcomes for future research. Future work: Further research should evaluate routine prophylaxis strategies for all eligible hospitalised patients. Models that could accurately identify individuals at very low risk of blood clots (who could discontinue prophylaxis) warrant further evaluation. Study registration: This study is registered as PROSPERO CRD42020165778 and Researchregistry5216. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127454) and will be published in full in Health Technology Assessment; Vol. 28, No. 20. See the NIHR Funding and Awards website for further award information.

People who are admitted to hospital are at risk of blood clots that can cause serious illness or death. Patients are often given low doses of blood-thinning drugs to reduce this risk. However, these drugs can cause side effects, such as bleeding. Hospitals currently use complex risk assessment models (risk scores, which usually include patient, disease, mobility and intervention factors) to determine the individual risk of blood clots and identify people most likely to benefit from blood-thinning drugs. There are a lot of different risk scores and we do not know which one is best. We also do not know how these scores compare to each other or whether using scores to decide who should get blood-thinning drugs provides good value for money to the NHS. We reviewed all previous studies of risk scores. We found that they did not predict blood clots very well and we could not recommend one score over another. We then created a mathematical model to simulate the use of blood-thinning drugs in people admitted to hospital. The model suggested that giving blood-thinning drugs to everyone who could have them would probably provide the best value for money, in medical patients. Our findings were the same, but less certain, for surgical patients. We also collected information from four NHS hospitals to explore possibilities for future research. Our work showed that routinely collected electronic data on blood clots and bleeding events is not very accurate and that using different scores could result in variable use of blood-thinning medications. Our findings suggest that it may be better value to the NHS and better for patients if we were to offer blood-thinning medications to everyone on admission to hospital, without using any risk score. However, this approach needs further research to ensure it is safe and effective. Such research would not be able to rely on routine electronic data to identify blood clots or bleeding events, in isolation.

Predictive performance of the common red flags in emergency department headache patients: a HEAD and HEAD-Colombia study.

OBJECTIVES: Only a small proportion of patients presenting to an ED with headache have a serious cause. The SNNOOP10 criteria, which incorporates red and orange flags for serious causes, has been proposed but not well studied. This project aims to compare the proportion of patients with 10 commonly accepted red flag criteria (singly and in combination) between patients with and without a diagnosis of serious secondary headache in a large, multinational cohort of ED patients presenting with headache. METHODS: Secondary analysis of data obtained in the HEAD and HEAD-Colombia studies. The outcome of interest was serious secondary headache. The predictive performance of 10 red flag criteria from the SNNOOP10 criteria list was estimated individually and in combination. RESULTS: 5293 patients were included, of whom 6.1% (95% CI 5.5% to 6.8%) had a defined serious cause identified. New neurological deficit, history of neoplasm, older age (>50 years) and recent head trauma (2-7 days prior) were independent predictors of a serious secondary headache diagnosis. After adjusting for other predictors, sudden onset, onset during exertion, pregnancy and immune suppression were not associated with a serious headache diagnosis. The combined sensitivity of the red flag criteria overall was 96.5% (95% CI 93.2% to 98.3%) but specificity was low, 5.1% (95% CI 4.3% to 6.0%). Positive predictive value was 9.3% (95% CI 8.2% to 10.5%) with negative predictive value of 93.5% (95% CI 87.6% to 96.8%). CONCLUSION: The sensitivity and specificity of the red flag criteria in this study were lower than previously reported. Regarding clinical practice, this suggests that red flag criteria may be useful to identify patients at higher risk of a serious secondary headache cause, but their low specificity could result in increased rates of CT scanning. TRIAL REGISTRATION NUMBER: ANZCTR376695.

Venous thromboembolism chemical prophylaxis after skull base surgery.

PURPOSE: There is no guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using pharmacological agents (chemoprophylaxis) in patients undergoing skull base surgery. The aim of this study was to compare VTE and intracranial haematoma rates after skull base surgery in patients treated with/without chemoprophylaxis. METHODS: Review of prospective quaternary centre database including adults undergoing first-time skull base surgery (2009-2020). VTE was defined as deep vein thrombosis (DVT) and pulmonary embolism (PE) within 6 months of surgery. Multivariate logistic regression was used to determine factors predictive of postoperative intracranial haematoma/VTE. Propensity score matching (PSM) was used in group comparisons. RESULTS: One thousand five hundred fifty-one patients were included with a median age of 52 years (range 16-89 years) and female predominance (62%). Postoperative chemoprophylaxis was used in 81% of patients at a median of 1 day postoperatively. There were 12 VTE events (1.2%), and the use of chemoprophylaxis did not negate the risk of VTE entirely (p > 0.99) and was highest on/after postoperative day 6 (9/12 VTE events). There were 18 intracranial haematomas (0.8%), and after PSM, chemoprophylaxis did not significantly increase the risk of an intracranial haematoma (p > 0.99). Patients administered chemoprophylaxis from postoperative days 1 and 2 had similar rates of intracranial haematomas (p = 0.60) and VTE (p = 0.60), affirmed in PSM. CONCLUSION: Postoperative chemoprophylaxis represents a relatively safe strategy in patients undergoing skull base surgery. We advocate a personalised approach to chemoprophylaxis and recommend it on postoperative days 1 or 2 when indicated.

Best Evidence Topic report: Antithrombotic therapy and endovascular intervention for blunt cerebrovascular injury.

A short cut review of the literature was carried out to examine the evidence supporting antithrombotic treatment and/or endovascular therapy to reduce mortality and/or prevent future stroke following blunt cerebrovascular injury (BCVI). Five papers were identified as suitable for inclusion using the reported search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the best papers are tabulated. It is concluded that in patients with BCVI confirmed by CT angiography, there is limited evidence to support screening for, or treating BCVI. In confirmed BCVI where the risk of stroke is felt to outweigh the risk of bleeding, antiplatelet therapy appears to be as effective as therapeutic anticoagulation.

Effectiveness and cost effectiveness of pharmacological thromboprophylaxis for medical inpatients: decision analysis modelling study.

Objective: To determine the balance of costs, risks, and benefits for different thromboprophylaxis strategies for medical patients during hospital admission. Design: Decision analysis modelling study. Setting: NHS hospitals in England. Population: Eligible adult medical inpatients, excluding patients in critical care and pregnant women. Interventions: Pharmacological thromboprophylaxis (low molecular weight heparin) for all medical inpatients, thromboprophylaxis for none, and thromboprophylaxis given to higher risk inpatients according to risk assessment models (Padua, Caprini, IMPROVE, Intermountain, Kucher, Geneva, and Rothberg) previously validated in medical cohorts. Main outcome measures: Lifetime costs and quality adjusted life years (QALYs). Costs were assessed from the perspective of the NHS and Personal Social Services in England. Other outcomes assessed were incidence and treatment of venous thromboembolism, major bleeds including intracranial haemorrhage, chronic thromboembolic complications, and overall survival. Results: Offering thromboprophylaxis to all medical inpatients had a high probability (>99%) of being the most cost effective strategy (at a threshold of £20 000 (€23 440; $25 270) per QALY) in the probabilistic sensitivity analysis, when applying performance data from the Padua risk assessment model, which was typical of that observed across several risk assessment models in a medical inpatient cohort. Thromboprophylaxis for all medical inpatients was estimated to result in 0.0552 additional QALYs (95% credible interval 0.0209 to 0.1111) while generating cost savings of £28.44 (-£47 to £105) compared with thromboprophylaxis for none. No other risk assessment model was more cost effective than thromboprophylaxis for all medical inpatients when assessed in deterministic analysis. Risk based thromboprophylaxis was found to have a high (76.6%) probability of being the most cost effective strategy only when assuming a risk assessment model with very high sensitivity is available (sensitivity 99.9% and specificity 23.7% v base case sensitivity 49.3% and specificity 73.0%). Conclusions: Offering pharmacological thromboprophylaxis to all eligible medical inpatients appears to be the most cost effective strategy. To be cost effective, any risk assessment model would need to have a very high sensitivity resulting in widespread thromboprophylaxis in all patients except those at the very lowest risk, who could potentially avoid prophylactic anticoagulation during their hospital stay.

Plasma interleukin responses as predictors of outcome stratification in patients after major trauma: a prospective observational two centre study.

Background and objectives: There is a need to develop objective risk stratification tools to define efficient care pathways for trauma patients. Biomarker-based point of care testing may strengthen existing clinical tools currently available for this purpose. The dysregulation of pro- and anti-inflammatory cytokines in the pathogenesis of organ failure is well recognised. This study was carried out to evaluate whether blood concentrations of IL-6, IL-10, and IL-6:IL-10 ratios in the early stages of the illness are significantly different in patients with worsening organ function. Materials and methods: In this prospective observational cohort study, plasma concentrations of IL-6 and IL-10 on days 1, 3 and 5 were measured in 91 major trauma patients using a multiplexed cytometric bead array approach. A composite measure of adverse outcome - defined as SOFA ≥ 2 or mortality at 7 days, was the primary outcome. IL-6 and IL-10 concentrations in early samples (days 1, 3 & 5) in patients who developed SOFA ≥ 2 on day 7 were compared against those who did not. Similar composite outcome groups at day 5 and in groups with worsening or improving SOFA scores (ΔSOFA) at days 7 and 5 were undertaken as secondary analyses. Results: Stratification on day 7, 44 (48%) patients showed adverse outcomes. These adverse outcomes associated with significantly greater IL-6 concentrations on days 1 and 5 (Day 1: 47.65 [23.24-78.68] Vs 73.69 [39.93 - 118.07] pg/mL, P = 0.040 and Day 5: 12.85 [5.80-19.51] Vs 28.90 [8.78-74.08] pg/mL; P = 0.0019). Similarly, IL-10 levels were significantly greater in the adverse outcome group on days 3 and 5 (Day 3: 2.54 [1.76-3.19] Vs 3.16 [2.68-4.21] pg/mL; P = 0.044 and Day 5: 2.03 [1.65-2.55] Vs 2.90 [2.00-5.06] pg/mL; P <0.001). IL-6 and IL-10 concentrations were also significantly elevated in the adverse outcome groups at day 3 and day 5 when stratified on day 5 outcomes. Both IL-6 and IL-6:IL-10 were found to be significantly elevated on days 1 and 3 when stratified based on ΔSOFA at day 5. This significance was lost when stratified on day 7 scores. Conclusions: Early IL-6 and IL-10 concentrations are significantly greater in patients who develop worsening organ functions downstream. These differences may provide an alternate biomarker-based approach to strengthen risk stratification in trauma patients.

Computed tomography brain scan utilization in patients with headache presenting to emergency departments: a multinational study.

BACKGROUND AND IMPORTANCE: Recommended indications for emergency computed tomography (CT) brain scans are not only complex and evolving, but it is also unknown whether they are being followed in emergency departments (EDs). OBJECTIVE: To determine the CT utilization and diagnostic yield in the ED in patients with headaches across broad geographical regions. DESIGN: Secondary analysis of data from a multinational cross-sectional study of ED headache presentations over one month in 2019. SETTING AND PARTICIPANTS: Hospitals from 10 participating countries were divided into five geographical regions [Australia and New Zealand (ANZ); Colombia; Europe: Belgium, France, UK, and Romania; Hong Kong and Singapore (HKS); and Turkey). Adult patients with nontraumatic headache as the primary presenting complaint were included. Patients were identified from ED management systems. OUTCOME MEASURES AND ANALYSIS: The outcome measures were CT utilization and diagnostic yield. CT utilization was calculated using a multilevel binary logistic regression model to account for clustering of patients within hospitals and regions. Imaging data (CT requests and reports) were sourced from radiology management systems. MAIN RESULTS: The study included 5281 participants. Median (interquartile range) age was 40 (29-55) years, 66% were women. Overall mean CT utilization was 38.5% [95% confidence interval (CI), 30.4-47.4%]. Regional utilization was highest in Europe (46.0%) and lowest in Turkey (28.9%), with HKS (38.0%), ANZ (40.0%), and Colombia (40.8%) in between. Its distribution across hospitals was approximately symmetrical. There was greater variation in CT utilization between hospitals within a region than between regions (hospital variance 0.422, region variance 0.100). Overall mean CT diagnostic yield was 9.9% (95% CI, 8.7-11.3%). Its distribution across hospitals was positively skewed. Regional yield was lower in Europe (5.4%) than in other regions: Colombia (9.1%), HKS (9.7%), Turkey (10.6%), and ANZ (11.2%). There was a weak negative correlation between utilization and diagnostic yield ( r  = -0.248). CONCLUSION: In this international study, there was a high variation (28.9-46.6%) in CT utilization and diagnostic yield (5.4-11.2%) across broad geographic regions. Europe had the highest utilization and the lowest yield. The study findings provide a foundation to address variation in neuroimaging in ED headache presentations.

Albumin versus balanced crystalloid for resuscitation in the treatment of sepsis: A protocol for a randomised controlled feasibility study, "ABC-Sepsis".

Background: Patients presenting with suspected sepsis to secondary care often require fluid resuscitation to correct hypovolaemia and/or septic shock. Existing evidence signals, but does not demonstrate, a benefit for regimes including albumin over balanced crystalloid alone. However, interventions may be started too late, missing a critical resuscitation window. Methods: ABC Sepsis is a currently recruiting randomised controlled feasibility trial comparing 5% human albumin solution (HAS) with balanced crystalloid for fluid resuscitation in patients with suspected sepsis. This multicentre trial is recruiting adult patients within 12 hours of presentation to secondary care with suspected community acquired sepsis, with a National Early Warning Score ≥5, who require intravenous fluid resuscitation. Participants are randomised to 5% HAS or balanced crystalloid as the sole resuscitation fluid for the first 6 hours. Objectives: Primary objectives are feasibility of recruitment to the study and 30-day mortality between groups. Secondary objectives include in-hospital and 90-day mortality, adherence to trial protocol, quality of life measurement and secondary care costs. Discussion: This trial aims to determine the feasibility of conducting a trial to address the current uncertainty around optimal fluid resuscitation of patients with suspected sepsis. Understanding the feasibility of delivering a definitive study will be dependent on how the study team are able to negotiate clinician choice, Emergency Department pressures and participant acceptability, as well as whether any clinical signal of benefit is detected.

Decision-analysis modeling of effectiveness and cost-effectiveness of pharmacologic thromboprophylaxis for surgical inpatients using variable risk assessment models or other strategies.

BACKGROUND: Surgical inpatients are at a risk of venous thromboembolism (VTE), which can be life-threatening or result in chronic complications. Thromboprophylaxis reduces the VTE risk but incurs costs and may increase bleeding risk. Risk assessment models (RAMs) are currently used to target thromboprophylaxis at high-risk patients. OBJECTIVES: To determine the balance of cost, risk, and benefit for different thromboprophylaxis strategies in adult surgical inpatients, excluding patients who underwent major orthopedic surgery or were under critical care and pregnant women. METHODS: Decision analytic modeling was performed to estimate the following outcomes for alternative thromboprophylaxis strategies: thromboprophylaxis usage; VTE incidence and treatment; major bleeding; chronic thromboembolic complications; and overall survival. Strategies compared were as follows: no thromboprophylaxis; thromboprophylaxis for all; and thromboprophylaxis given according to RAMs (Caprini and Pannucci). Thromboprophylaxis is assumed to be given for the duration of hospitalization. The model evaluates lifetime costs and quality-adjusted life-years (QALYs) within England's health and social care services. RESULTS: Thromboprophylaxis for all surgical inpatients had a 70% probability of being the most cost-effective strategy (at a £20 000 per QALY threshold). RAM-based prophylaxis would be the most cost-effective strategy if a RAM with a higher sensitivity (99.9%) were available for surgical inpatients. QALY gains were mainly due to reduced postthrombotic complications. The optimal strategy was sensitive to several other factors such as the risk of VTE, bleeding and postthrombotic syndrome, duration of prophylaxis, and patient age. CONCLUSION: Thromboprophylaxis for all eligible surgical inpatients seemed to be the most cost-effective strategy. Default recommendations for pharmacologic thromboprophylaxis, with the potential to opt-out, may be superior to a complex risk-based opt-in approach.

Accuracy of efficient data methods to determine the incidence of hospital-acquired thrombosis and major bleeding in medical and surgical inpatients: a multicentre observational cohort study in four UK hospitals.

OBJECTIVES: We evaluated the accuracy of using routine health service data to identify hospital-acquired thrombosis (HAT) and major bleeding events (MBE) compared with a reference standard of case note review. DESIGN: A multicentre observational cohort study. SETTING: Four acute hospitals in the UK. PARTICIPANTS: A consecutive unselective cohort of general medical and surgical patients requiring hospitalisation for a period of >24 hours during the calendar year 2021. We excluded paediatric, obstetric and critical care patients due to differential risk profiles. INTERVENTIONS: We compared preidentified sources of routinely collected information (using hospital coding data and local contractually mandated thrombosis datasets) to data extracted from case notes using a predesigned workflow methodology. PRIMARY AND SECONDARY OUTCOME MEASURES: We defined HAT as objectively confirmed venous thromboembolism occurring during hospital stay or within 90 days of discharge and MBE as per international consensus. RESULTS: We were able to source all necessary routinely collected outcome data for 87% of 2008 case episodes reviewed. The sensitivity of hospital coding data (International Classification of Diseases 10th Revision, ICD-10) for the diagnosis of HAT and MBE was 62% (95% CI, 54 to 69) and 38% (95% CI, 27 to 50), respectively. Sensitivity improved to 81% (95% CI, 75 to 87) when using local thrombosis data sets. CONCLUSIONS: Using routinely collected data appeared to miss a substantial proportion of outcome events, when compared with case note review. Our study suggests that currently available routine data collection methods in the UK are inadequate to support efficient study designs in venous thromboembolism research. TRIAL REGISTRATION NUMBER: NIHR127454.

Pulmonary embolism management in the emergency department: part 2.

Pulmonary embolism (PE) can present with a range of severity. Prognostic risk stratification is important for efficacious and safe management. This second of two review articles discusses the management of high-, intermediate- and low-risk PE. We discuss strategies to identify patients suitable for urgent outpatient care in addition to identification of patients who would benefit from thrombolysis. We discuss specific subgroups of patients where optimal treatment differs from the usual approach and identify emerging management paradigms exploring new therapies and subgroups.

Deep vein thrombosis and pulmonary embolism: a prospective, observational study to evaluate diagnostic performance of the Tina-quant D-Dimer Gen.2 assay.

Background: D-Dimer testing is a diagnostic tool for exclusion of deep vein thrombosis (DVT) and pulmonary embolism (PE). This study evaluated the diagnostic performance of the Tina-quant® D-Dimer Gen.2 assay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) in patients with low/intermediate pre-test probability of DVT/PE using standard, age-, and clinical probability-adjusted cut-offs. Methods: In this prospective, observational, multicenter study (July 2017-August 2019), plasma samples were collected from hospital emergency departments and specialist referral centers. DVT/PE was diagnosed under hospital standard procedures and imaging protocols. A standard D-dimer cut-off of 0.5 µg fibrinogen equivalent units (FEU)/ml was combined with the three-level Wells score; cut-offs adjusted for age (age × 0.01 µg FEU/ml for patients >50 years) and clinical probability (1 µg FEU/ml for low probability) were also evaluated. An assay comparison was conducted in a subset of samples using the Tina-quant D-Dimer Gen.2 assay and the previously established routine laboratory assay, STA-Liatest D-Di Plus assay (Stago Deutschland GmbH, Düsseldorf, Germany). Results: 2,897 patients were enrolled; 2,516 completed the study (DVT cohort: 1,741 PE cohort: 775). Clinical assessment plus D-dimer testing using the standard cut-off resulted in 317 (DVT) and 230 (PE) false positives, and zero (DVT) and one (PE) false negatives. Negative predictive value (NPV) was 100.0% (95% confidence interval [CI]: 99.7%-100.0%) and 99.8% (95% CI: 98.8%-100.0%) for DVT and PE, respectively. After age-adjustment, NPV was 99.9% (95% CI: 99.6%-100.0%) and 99.1% (95% CI: 97.8-99.7) for DVT and PE, respectively. False positive rates decreased (>50%) in clinical probability-adjusted analyses vs. primary analysis. In the assay comparison, the performances of the two assays were comparable. Conclusion: The Tina-quant D-Dimer Gen.2 assay and standard D-dimer cut-off level combined with the three-level Wells score accurately identified patients with a very low probability of DVT/PE.

The application of an age adjusted D-dimer threshold to rule out suspected venous thromboembolism (VTE) in an emergency department setting: a retrospective diagnostic cohort study.

BACKGROUND: Venous Thromboembolic disease (VTE) poses a diagnostic challenge for clinicians in acute care. Over reliance on reference standard investigations can lead to over treatment and potential harm. We sought to evaluate the pragmatic performance and implications of using an age adjusted D-dimer (AADD) strategy to rule out VTE in patients with suspected disease attending an emergency department (ED) setting. We aimed to determine diagnostic test characteristics and assess whether this strategy would result in proportional imaging reduction and potential cost savings. METHODS: Design: Single centre retrospective diagnostic cohort study. All patients > 50 years old evaluated for possible VTE who presented to the emergency department over a consecutive 12-month period between January and December 2016 with a positive D-dimer result. Clinical assessment records and reference standard imaging results were followed up by multiple independent adjudicators and coded as VTE positive or negative. RESULTS: During the study period, there were 2132 positive D-dimer results. One thousand two hundred thirty-six patients received reference standard investigations. A total increase of 314/1236 (25.1%) results would have been coded as true negatives as opposed to false positive if the AADD cut off point had been applied, with 314 reference standard tests subsequently avoided. The AADD cut off had comparable sensitivity to the current cut off despite this increase in specificity; sensitivities for the diagnosis of DVT were 99.28% (95% CI 96.06-99.98%) and 97.72% for PE (95% CI 91.94% to 97.72). There were 3 false negative results using the AADD strategy. CONCLUSIONS: In patients with suspected VTE with a low or moderate pre-test probability, the application of AADD appears to increase the proportion of patients in which VTE can be excluded without the need for reference standard imaging. This management strategy is likely to be associated with substantial reduction in anticoagulation treatment, investigations and cost/time savings.