Multicenter Prospective Observational Cohort Study Research Articles

The Detrimental Impact of the COVID‐19 Pandemic on Major Trauma Outcomes in the Netherlands: A Comprehensive Nationwide Study

Background: The COVID-19 pandemic had a profound impact on healthcare in general and on the availability of emergency services. Immediate access to specialised services, including intensive care unit (ICUs), is potentially endangered during a pandemic. Severely injured patients highly rely on these resources, shortage may influence their outcome. We therefore evaluated the impact of the COVID-19 pandemic on the outcome of major trauma patients.Methods: A nationwide comprehensive multi-centre prospective observational cohort study, based on the Dutch National Trauma Registry was performed to compare the patient characteristics, resource usage, and outcome of major trauma patients treated at all trauma-receiving hospitals during the first COVID-19 peak (March 23rd through May 10th) in 2020 versus pre–COVID-19 reference periods in 2018 and 2019.Findings: During the COVID-19 peak period, 502 major trauma patients were admitted, versus 566 on average in the pre-COVID-19 years. Significantly fewer patients were admitted to ICU facilities during the peak than during the reference period (46·1% versus 53·3%; p=0·008). The subgroup of 155 major trauma patients with less severe brain injuries (abbreviated injury score ≤3) were in particular less often admitted to the ICU during the peak (36·1% vs 52 ·1%; p=0·001). Moreover, this subgroup showed increased mortality compared to the reference group (14·2% vs 7·7%; p=0·023). In addition, a significant increase in observed versus predicted mortality was also recorded for patients who had a priori predicted mortality of 50% to 75% (p=0·012).Interpretation: We speculate that the restricted availability of ICU beds negatively influenced the outcome of major trauma patients during the COVID-19 peak in 2020. In particular for patients with less severe traumatic brain injuries or with a high mortality probability.Funding: None to declare. Declaration of Interest: All authors declare no conflict of interest, including financial, consultant, institutional, and other relationships that might lead to bias or conflict of interestEthical Approval: This study was approved by the Scientific Advisory Board, as well as the Board of the Dutch Emergency Care Network.

Clinical Predictors of Encephalitis in UK Adults – A Multi-Centre Prospective Observational Cohort Study

Background: Encephalitis, brain inflammation and swelling, most often caused by an infection or the body’s immune defences, can have devastating consequences, especially if diagnosed late. We looked for clinical predictors of different types of encephalitis to help clinicians consider earlier treatment. Methods: We conducted a multicentre prospective observational cohort study (ENCEPH-UK) of adults (> 16 years) with suspected encephalitis at 31 UK hospitals. We evaluated clinical features and investigated for infectious and autoimmune causes. Findings: 341 patients were enrolled between December 2012 and December 2015 and followed up for 12 months. 233 had encephalitis, of whom 65 (28%) had herpes simplex virus (HSV), 38 (16%) had confirmed or probable autoimmune encephalitis, and 87 (37%) had no cause found. The median time from admission to 1st dose of aciclovir for those with HSV was 14 hours (IQR 5-50); time to 1st dose of immunosuppressant for the autoimmune group was 125 hours (IQR 45-250). Compared to non-HSV encephalitis, patients with HSV more often had fever, lower serum sodium and lacked a rash. Those with probable or confirmed autoimmune encephalitis were more likely to be female, have abnormal movements, normal serum sodium levels and a cerebrospinal fluid white cell count < 20 cells x106/L, but they were less likely to have a febrile illness. Interpretation: Initiation of treatment for autoimmune encephalitis is delayed considerably compared with HSV encephalitis. Clinical features can help identify patients with autoimmune disease and could be used to initiate earlier presumptive therapy. Clinical Trial Registration Details: Funding Information: National Institute for Health Research, UK. Declaration of Interests: None to declare. Ethics Approval Statement: The study protocols were approved by participating sites and the National Research Ethics Service (now part of the Health Research Authority) East Midlands Nottingham 1 committee (reference 11/EM/0442). Written consent for entry into the study was obtained from patients or an accompanying relative.

An original risk scheme to predict in-hospital major bleeding in acute pulmonary embolism: The Syncope, Troponin, Anemia, Anti-platelet therapy, Renal dysfunction (STAR) bleeding score

Bleeding-prediction score may help guiding management of patients with acute pulmonary embolism (PE). We aimed to develop the first risk stratification scheme to predict in-hospital major bleeding in PE. We recorded in-hospital characteristics of 2754 PE patients included in a prospective observational multicenter cohort study contributing 18,028 person-days of follow-up. Bleeding events were independently adjudicated using medical record review. We used the best subsets logistic regression to select candidates included in the in-hospital major bleeding score. The final model was internally validated by bootstrapping (500 replicates) and compared to the PE-derived long-term bleeding RIETE and VTE-BLEED scores. We observed 82 first in-hospital major bleeding [3.0% (95% CI, 2.4–3.7]. Five independent variables were included in the final model and weighted by regression coefficients: anemia (hemoglobin < 12 g/dL) (2.5 points), syncope (2 points), concomitant medication usage predisposing to bleeding (1.5 points), renal dysfunction (eGFRCKD-EPI < 60 ml.min-1) (1 point), and positive troponin (1 point) (i.e., STAR bleeding score). Major bleeding rates ranged from 0.4% (0 point) to 15.6% (≥ 6 points). Collapsed into a 3-category risk score, major bleeding rates were 0.87% in the low risk group (0–1.5 points), 3.9% in intermediate risk (2–3 points), and 8.1% in high risk (> 3 points). The C-index for the continuous risk score was 0.78 and remained good (i.e., 0.75) in the bootstrapped internal validation. The global fit of the STAR bleeding score was significantly higher than those of the RIETE and VTE-BLED scores allowing net reclassification improvement of major bleeding predicted probabilities (37% and 41%, respectively). A simple 5-variable risk score was effective in quantifying the risk of PE-related in-hospital major bleeding in a large community-based cohort of patients. External validations are warranted.

Accuracy of available scoring systems for prediction of in-hospital major bleeding in acute pulmonary embolism patients

Bleeding prediction scores may help guide acute management of patients with pulmonary embolism (PE). However existing scoring systems have not been validated for in-hospital assessment. We compared 6 available bleeding scores for the prediction of major bleeding in the in-hospital phase in a real-life cohort. We recorded in-hospital characteristics of 2754 PE patients included in a prospective observational multicenter cohort study contributing 18,028 person-days of follow-up. The VTE-BLEED, RIETE, ORBIT, HEMORR 2 HAGES, ATRIA, and HAS-BLED scores were assessed at baseline. ISTH-defined bleeding events were independently adjudicated. The accuracy of the overall, original 3-level and newly defined optimal 2-level outcome of the scores were evaluated and compared. We observed 82 first in-hospital major bleeding events [3.0% (95% CI, 2.4–3.7)]. Overall, the predictive power of bleeding scores was poor, with a Harrel's C index ranging from 0.57 to 0.69. The Riete score had the numerically highest model fit and discrimination capacity but without reaching statistical significance versus the ORBIT, HEMORR 2 HAGES, and ATRIA scores. The VTE-BLEED and HAS-BLED scores had significantly lower C indices, integrated discrimination improvement, and net reclassification improvement compared to the others. The rate of observed in-hospital major bleeding in score-defined low-risk patients was high, at between 15% to 34%. Current available scoring systems are not sufficiently accurate for the prediction of in-hospital major bleeding in patients with acute PE. There is a need to develop risk scores specific to acute PE to optimally target bleeding-prevention strategies.

The Prevalence, Risk Factors, and Outcomes of Sepsis in Critically Ill Patients in China: A Multicenter Prospective Cohort Study

Background: Sepsis is a main cause of morbidity and mortality in critically ill patients. The epidemiology of sepsis in high-income countries is well-known, but information on sepsis in middle- or low-income countries is still deficient, especially in China. The purpose of this study was to explore the prevalence, characteristics, risk factors, treatment, and outcomes of sepsis in critically ill patients in tertiary hospitals in China.Methods: A multicenter prospective observational cohort study was performed with consecutively collected data from adults who stayed in any intensive care unit (ICU) for at least 24 h; data were collected from 1 January 2014 to 31 August 2015, and patients were followed until death or discharge from the hospital.Results: A total of 4,910 patients were enrolled in the study. Of these, 2,086 (42.5%) presented with sepsis or septic shock on admission to the ICU or within the first 48 h after admission to the ICU. ICU mortality was higher in patients with sepsis (13.1%) and septic shock (39.0%) and varied according to geographical region. Acinetobacter, Pseudomonas, and Staphylococcus infections were associated with increased ICU mortality. In addition, age, Acute Physiology, and Chronic Health Evaluation II (APACHE II) scores, pre-existing cardiovascular diseases, malignant tumors, renal replacement therapy (RRT), and septic shock were independent risk factors for mortality in patients with sepsis. The prompt administration of antibiotics (OR 0.65, 95% CI 0.46–0.92) and 30 mL/kg of initial fluid resuscitation during the first 3 h (OR 0.43, 95% CI 0.30–0.63) improved the outcome in patients with septic shock.Conclusions: Sepsis was common and was associated with a high mortality rate in critically ill patients in tertiary hospitals in China. The prompt administration of antibiotics and 30 mL/kg fluid resuscitation decreased the risk of mortality.

Insulin-like growth factor-binding protein 7 and risk of congestive heart failure hospitalization in patients with atrial fibrillation

The occurrence of congestive heart failure (CHF) hospitalization among patients with atrial fibrillation (AF) is a poor prognostic marker. The purpose of this study was to assess whether insulin-like growth factor-binding protein 7 (IGFBP-7), a marker of myocardial damage, identifies AF patients at high risk for this complication. We analyzed 2 prospective multicenter observational cohort studies that included 3691 AF patients. Levels of IGFBP-7 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured from frozen plasma samples at baseline. The primary endpoint was hospitalization for CHF. Multivariable adjusted Cox regression analyses were constructed. Mean patient age was 69 ± 12 years, 1028 (28%) were female, and 879 (24%) had a history of CHF. The incidence per 1000 patient-years across increasing IGFBP-7 quartiles was 7, 10, 32, and 85. The corresponding multivariable adjusted hazard ratios (aHRs) (95% confidence interval [CI]) were 1.0, 1.05 (0.63-1.77), 2.38 (1.50-3.79), and 4.37 (2.72-7.04) (P for trend <.001). In a subgroup of 2812 patients without pre-existing CHF at baseline, the corresponding aHRs were 1.0, 0.90 (0.47-1.72), 1.69 (0.94-3.04), and 3.48 (1.94-6.24) (P for trend <.001). Patients with IGFBP-7 and NT-proBNP levels above the biomarker-specific median had a higher risk of incident CHF hospitalization (aHR 5.20; 3.35-8.09) compared to those with only 1 elevated marker (elevated IGFBP-7 aHR 2.17; 1.30-3.60); elevated NT-proBNP aHR 1.97; 1.17-3.33); or no elevated marker (reference). Higher plasma levels of IGFBP-7 were strongly and independently associated with CHF hospitalization in AF patients. The prognostic information provided by IGFBP-7 was additive to that of NT-proBNP.

PDG7 Multicenter Prospective Observational Double Cohort Study to Evaluate the Associations between Clinical Characteristics and Use of ORAL Anticoagulants in Italian Elderly Patients Suffering from NVAF. Presbus Study Design

PDG7 Multicenter Prospective Observational Double Cohort Study to Evaluate the Associations between Clinical Characteristics and Use of ORAL Anticoagulants in Italian Elderly Patients Suffering from NVAF. Presbus Study Design

Early abolition of cough reflex predicts mortality in deeply sedated brain-injured patients.

BackgroundDeep sedation may hamper the detection of neurological deterioration in brain-injured patients. Impaired brainstem reflexes within the first 24 h of deep sedation are associated with increased mortality in non-brain-injured patients. Our objective was to confirm this association in brain-injured patients.MethodsThis was an observational prospective multicenter cohort study involving four neuro-intensive care units. We included acute brain-injured patients requiring deep sedation, defined by a Richmond Assessment Sedation Scale (RASS) < −3. Neurological assessment was performed at day 1 and included pupillary diameter, pupillary light, corneal and cough reflexes, and grimace and motor response to noxious stimuli. Pre-sedation Glasgow Coma Scale (GCS) and Simplified Acute Physiology Score (SAPS-II) were collected, as well as the cause of death in the Intensive Care Unit (ICU).ResultsA total of 137 brain-injured patients were recruited, including 70 (51%) traumatic brain-injured patients, 40 (29%) vascular (subarachnoid hemorrhage or intracerebral hemorrhage). Thirty patients (22%) died in the ICU. At day 1, the corneal (OR 2.69, p = 0.034) and cough reflexes (OR 5.12, p = 0.0003) were more frequently abolished in patients that died in the ICU. In a multivariate analysis, abolished cough reflex was associated with ICU mortality after adjustment to pre-sedation GCS, SAPS-II, RASS (OR: 5.19, 95% CI [1.92–14.1], p = 0.001) or dose of sedatives (OR: 8.89, 95% CI [2.64–30.0], p = 0.0004).ConclusionEarly (day 1) cough reflex abolition is an independent predictor of mortality in deeply sedated brain-injured patients. Abolished cough reflex likely reflects a brainstem dysfunction that might result from the combination of primary and secondary neuro-inflammatory cerebral insults revealed and/or worsened by sedation.

Groin wound infection after vascular exposure (GIVE) multicentre cohort study.

Surgical site infections (SSIs) of groin wounds are a common and potentially preventable cause of morbidity, mortality, and healthcare costs in vascular surgery. Our aim was to define the contemporaneous rate of groin SSIs, determine clinical sequelae, and identify risk factors for SSI.An international multicentre prospective observational cohort study of consecutive patients undergoing groin incision for femoral vessel access in vascular surgery was undertaken over 3 months, follow‐up was 90 days. The primary outcome was the incidence of groin wound SSI.1337 groin incisions (1039 patients) from 37 centres were included. 115 groin incisions (8.6%) developed SSI, of which 62 (4.6%) were superficial. Patients who developed an SSI had a significantly longer length of hospital stay (6 versus 5 days, P = .005), a significantly higher rate of post‐operative acute kidney injury (19.6% versus 11.7%, P = .018), with no significant difference in 90‐day mortality. Female sex, Body mass index≥30 kg/m2, ischaemic heart disease, aqueous betadine skin preparation, bypass/patch use (vein, xenograft, or prosthetic), and increased operative time were independent predictors of SSI.Groin infections, which are clinically apparent to the treating vascular unit, are frequent and their development carries significant clinical sequelae. Risk factors include modifiable and non‐modifiable variables.

Effect of intravenous thrombolysis in stroke depends on pattern of intracranial internal carotid artery calcification

Background and aimsThe pattern of intracranial internal carotid artery calcification (ICAC) has been identified as an effect modifier of endovascular treatment in patients with acute ischemic stroke, but it is unclear whether it modifies the effect of intravenous thrombolysis. The purpose of this study was to evaluate the association between intravenous thrombolysis and 90-day clinical outcome, follow-up infarct volume, intracranial hemorrhage and recanalization across different patterns of ICAC. MethodsPatients with acute ischemic stroke were selected from the Dutch acute stroke study, a prospective multicenter observational cohort study. ICAC pattern was determined on admission thin-slice non-contrast CT and categorized as absent, intimal, medial or indistinguishable. The primary outcome was the ordinal 90-day modified Rankin Scale. Other outcomes included follow-up infarct volume, intracranial hemorrhage, recanalization and collateral status. Associations were quantified with regression analyses and stratified by ICAC pattern. ResultsOf 982 patients, 609 (62%) received intravenous thrombolysis and 381 (39%) had a 90-day modified Rankin Scale of 3–6. Intravenous thrombolysis was associated with a lower 90-day modified Rankin Scale in the group without ICAC (adjusted OR 0.3; 95%-CI 0.1–0.9) and in the group with a medial ICAC pattern (adjusted OR 0.5; 95%-CI 0.3–0.8), but not in the groups with intimal (adjusted OR 0.9; 95%-CI 0.5–1.5) or indistinguishable patterns (adjusted OR 0.6; 95%-CI 0.2–1.8). The associations between intravenous thrombolysis and follow-up infarct volume and intracranial hemorrhage were not significant for any of the ICAC pattern groups. Intravenous thrombolysis was only associated with recanalization in the group with a medial ICAC pattern (adjusted OR 3.5; 95%-CI 1.2–11.0). Compared to an intimal ICAC pattern, a medial ICAC pattern was associated with good collateral status (adjusted OR 2.6; 95%-CI 1.1–6.0). ConclusionsIntravenous thrombolysis was significantly associated with favorable clinical outcome and successful recanalization in the group with a medial ICAC pattern, but not in the group with an intimal ICAC pattern.

Clinical outcomes of infection-related hospitalization in incident peritoneal dialysis patients.

BackgroundInfection is the second leading cause of death in patients undergoing long-term dialysis. Peritoneal dialysis (PD) is associated with an increased risk of infection-related hospitalization (IRH) when compared with hemodialysis. In this study, we investigated the influence of IRH on clinical outcomes in incident PD patients.MethodsIn total, 583 incident PD patients were selected from the Clinical Research Center Registry for End-Stage Renal Disease, a nationwide multicenter prospective observational cohort study in Korea. Incident PD patients who had been hospitalized for infection-related diseases were defined as the IRH group. The primary outcome was all-cause mortality and the secondary outcome was technical failure. The median follow-up period was 29 months.ResultsSeventy-three PD patients (12.5%) were categorized in the IRH group. Multivariable logistic regression analysis showed that diabetes mellitus was a significant independent predictor for IRH (odds ratio, 2.43; 95% confidence interval [CI], 1.12 to 5.29; P = 0.007). The most common causes of IRH were peritonitis (63.0%) and respiratory tract infection (9.6%). Multivariable Cox proportional hazard model analysis showed that IRH was a significant independent risk factor for all-cause mortality (hazard ratio [HR], 2.51; 95% CI, 1.12 to 5.62; P = 0.026) and for the technical failure of PD (HR, 3.23; 95% CI, 1.90 to 5.51; P < 0.001).ConclusionOur data showed that after initiation of PD, IRH was significantly associated with higher risk of all-cause mortality and technical failure.

Sex differences in ventricular remodeling and long-term heart failure outcomes following acute coronary syndrome

Abstract Background Compared with men, women are at increased risk of heart failure hospitalization following acute coronary syndrome (ACS). Purpose We sought to determine whether this increased hazard was associated with differing patterns in left ventricular (LV) remodeling over the first 12 months after ACS. Methods In a prospective multi-centre observational cohort study, 2,140 patients with ACS underwent echocardiography at 1, 4, and 12 months following the index event. Heart failure hospitalisation events were captured over a median 4.8 (IQR 3.4–6.5) years and relative risk compared between women and men using a multivariable Cox model adjusted for baseline demographics (age and systolic blood pressure) and echocardiographic variables (LV end diastolic and end systolic volumes, LV ejection fraction, interventricular septal wall thickness, and E/e') captured at baseline and 12 months. Results The 609 (28.5%) women were older (mean [SD] age 70 [12] versus 65 [12] years), had higher systolic blood pressure, demonstrated smaller increases in peak myocardial biomarkers, and were less likely to undergo coronary revascularization during the index admission (41.9% versus 62.0%; p&amp;lt;0.001 for all). After indexing for body surface area, women had smaller LV end diastolic and end systolic volumes, greater LV ejection fractions, and greater septal wall thickness and diastolic filling pressure estimates (E/e' 14 versus 11; p&amp;lt;0.001 for all). Diastolic volumes further diverged at 12 months (p=0.05) and septal wall thickness increased compared with men (p=0.016). In unadjusted and adjusted analyses women were at increased risk of future heart failure hospitalization (unadjusted HR 1.5, 95% CI 1.2–1.9, adjusted HR 1.6, 95% CI 1.1–2.4). Conclusions Women experience a more concentric remodeling pattern over the 12 months following ACS. Women remain at increased risk of long-term heart failure hospitalization after accounting for clinical and echocardiographic characteristics. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Heart Foundation of New Zealand, New Zealand Health Research Council

Age-related differences in ventricular remodeling and long-term heart failure outcomes following acute coronary syndrome

Abstract Background Older patients are at increased risk of heart failure hospitalization following acute coronary syndrome (ACS). Purpose We sought to determine whether this increased hazard was related to differing patterns in left ventricular (LV) remodeling over the first 12 months after ACS. Methods In a prospective multi-centre observational cohort study, 2,140 patients with ACS underwent echocardiography at 1, 4, and 12 months following the index event. Long-term heart failure hospitalisation events were captured for a median 4.8 (IQR 3.4–6.5) years and the relative risk compared between individuals ≤65 years and those &amp;gt;65 years using a multivariable Cox model adjusted for baseline clinical (sex, blood pressure, coronary revascularisation) and echocardiographic (LV end diastolic and end systolic volumes, LV ejection fraction, interventricular septal wall thickness, and E/e') variables recorded at baseline and 12 months. Results The 1177 (55%) participants who were &amp;gt;65 years were more likely to be women (34% versus 22%), had higher blood pressure, were more likely to present with non-ST elevation ACS, demonstrated smaller increases in peak myocardial biomarkers and were less likely to undergo coronary revascularization during the index admission (43.2% versus 72.3%; p&amp;lt;0.001 for all comparisons). At the 1 month visit, after indexing for body surface area, older patients had similar LV end diastolic but larger end systolic volumes (p=0.029), lower LV ejection fractions, and greater left ventricular mass and diastolic filling pressure estimates (E/e' 14 versus 10; p&amp;lt;0.001 for all) compared with the young. Systolic volumes appeared to further diverge at 12 months (p=0.064) however LV mass did not change in either group. In unadjusted analysis older patients were at increased risk of future heart failure hospitalization (HR 4.1, 95% CI 3.2–5.3). This increased risk persisted after adjustment for differences in baseline clinical and echocardiography data, and LV remodeling (adjusted HR 2.4, 95% CI 1.5–3.9). Conclusions Older patients experience a more eccentric remodeling pattern over the 12 months following ACS. Older individuals remain at increased risk of long-term heart failure hospitalization after accounting for clinical and echocardiographic characteristics. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): New Zealand Heart Foundation, New Zealand Health Research Council

Button battery ingestion in older people: Prospective study and management algorithm

People over 60 years old represent 4 to 16% of all incidents with button batteries. Significant necrotic lesions can appear as early as 2 hours following ingestion. This can induce esophagus perforation and lead to death. To determine cause of ingestion, clinical manifestations and outcome of button battery ingestion in older people. PilBouTox® was a 2 years prospective observational multicenter cohort study conducted by all French poison control centers for button battery ingestion in people aged 65 and over. After ingestion or insertion, patients were monitored for 21 days. We recorded cause of ingestion, button battery description, clinical manifestations, use of X-ray, endoscopy or surgery, duration of hospitalization and outcome. The patient mean age was 85 ± 7 years old with 64% being women. The incidence was 0.27 ingestion/100,000 aged people/year. In 82% of cases, only one battery was ingested. Seventy-six percent of the button batteries ingested came from the hearing aids. Ninety-four percent of patients were asymptomatic but 2 patients died: one unrelated and one potentially related. Three gastric endoscopies were performed, and one found distal esophagus lesion Forrest III. With simple precautionary advice, we can prevent 94% of button battery ingestions in older people. We proposed management algorithm for button battery ingestions in older people. Button battery ingestions appeared as an uncommon event. Button batteries ingestions can cause severe esophagus or gastric ulceration. Hearing aid batteries are mostly involved in older people without medical importance. Only one case of esophagus impaction needing endoscopic removal was recorded.

A Multicenter Prospective Observational Cohort Study to Investigate the Effectiveness and Safety of Rivaroxaban in Japanese Venous Thromboembolism Patients (The J'xactly Study).

There is insufficient real-world data on the current status of Japanese patients with venous thromboembolism (VTE) or its treatment and prevention with rivaroxaban.Methods and Results:In this multicenter, prospective, observational study conducted in Japan, 1,039 patients with acute symptomatic/asymptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE) with or without DVT prescribed rivaroxaban were enrolled at 152 institutions and observed for a median of 21.3 months. Mean age was 68.0±14.7 years, mean body weight was 60.3±14.1 kg, 59.0% were females, and 19.0% had active cancer. Incidences of recurrence or aggravation of symptomatic VTE (primary effectiveness outcome) and major bleeding (principal safety outcome) were 2.6% and 2.9% per patient-year, respectively. These outcomes did not differ between patients with DVT and those with PE (primary effectiveness outcome: 2.6% vs. 2.5% per patient-year, P=0.810; principal safety outcome: 3.5% vs. 2.4% per patient-year, P=0.394). The incidence of composite clinically relevant events, including recurrence or aggravation of symptomatic VTE, acute coronary syndrome, ischemic stroke, all-cause death, or major bleeding events, was 9.2% per patient-year. Multivariate analysis revealed that male sex, being underweight, having active cancer, chronic heart and lung disease, and previous stroke were independent determinants for composite clinically relevant events. In Japanese clinical practice, a single-drug approach with rivaroxaban was demonstrated to be a valuable treatment for a broad range of VTE patients.

Early detection of small volume stroke and thromboembolic sources with computed tomography: Rationale and design of the ENCLOSE study.

BackgroundComputed tomography is the most frequently used imaging modality in acute stroke imaging protocols. Detection of small volume infarcts in the brain and cardioembolic sources of stroke is difficult with current computed tomography protocols. Furthermore, the role of computed tomography findings to predict recurrent ischemic stroke is unclear. With ENCLOSE, we aim to improve (1) the detection of small volume infarcts with thin slice computed tomography perfusion (CTP) images and thromboembolic source with cardiac computed tomography techniques in the acute stage of ischemic stroke and (2) prediction of recurrent ischemic stroke with computed tomography-derived predictors.Methods/design: ENCLOSE is a prospective multicenter observational cohort study, which will be conducted in three Dutch stroke centers (ClinicalTrials.gov Identifier: NCT04019483). Patients (≥18 years) with suspected acute ischemic stroke who undergo computed tomography imaging within 9 h after symptom onset are eligible. Computed tomography imaging includes non-contrast CT, CTP, and computed tomography angiography (CTA) from base of the heart to the top of the brain. Dual-energy CT data will be acquired when possible, and thin-slice CTP reconstructions will be obtained in addition to standard 5 mm CTP data. CTP data will be processed with commercially available software and locally developed model-based methods. The post-processed thin-slice CTP images will be compared to the standard CTP images and to magnetic resonance diffusion-weighted imaging performed within 48 h after admission. Detection of cardioembolic sources of stroke will be evaluated on the CTA images. Recurrence will be evaluated 90 days and two years after the index event. The added value of imaging findings to prognostic models for recurrent ischemic stroke will be evaluated.ConclusionThe aim of ENCLOSE is to improve early detection of small volume stroke and thromboembolic sources and to improve prediction of recurrence in patients with acute ischemic stroke.

Prehospital Triage of Patients with Suspected Stroke (PRESTO): A Prospective In-Field Validation of Eight Prehospital Stroke Scales to Detect Intracranial Large Vessel Occlusion

Background: Due to the time-sensitive effect of endovascular treatment (EVT), rapid prehospital identification of large vessel occlusion (LVO) in suspected stroke patients is essential to optimize outcome. Inter-hospital transfers are an important cause of delay of EVT. Prehospital stroke scales have been proposed to select patients with LVO for direct transport to an endovascular-capable intervention centre. We aimed to prospectively validate eight prehospital stroke scales in the field. Methods: In a multi-centre prospective observational cohort study, we included suspected stroke patients transported by ambulance in the Southwest Netherlands. Paramedics assessed items from eight prehospital stroke scales: Rapid Arterial oCclusion Evaluation (RACE), Los Angeles Motor Scale (LAMS), Cincinnati Stroke Triage Assessment Tool (C-STAT), Gaze-Face-Arm-Speech-Time (G-FAST), Prehospital Acute Stroke Severity (PASS), Cincinnati Prehospital Stroke Scale (CPSS), Conveniently-Grasped Field Assessment Stroke Triage (CG-FAST), and the FAST PLUS Test. Patients that presented beyond six hours from symptom onset were excluded. Primary outcome was the clinical diagnosis of ischaemic stroke with a proximal intracranial LVO in the anterior circulation (aLVO) on CT-angiography. Prehospital stroke scale performance was expressed as the area under the receiver operating characteristic curve (AUC) and was compared with National Institute of Health Stroke Scale (NIHSS) scores assessed by physicians at the emergency department. Findings: We included 1039 patients, of which 121 patients (12%) were diagnosed with aLVO. AUCs for the prehospital stroke scales ranged from 0·69 (FAST PLUS) to 0·82 (RACE). The performance of RACE was not significantly different from G-FAST (AUC=0·80, p=0·14) and CG-FAST (AUC=0·80, p=0·09), but was significantly different from the other scales (p-values<0·05). The NIHSS performed somewhat better (AUC 0·86, p-values<0·05). Interpretation: Prehospital stroke scales detect aLVO with good accuracy and approach the performance of the physician-assessed NIHSS. RACE is the best performing prehospital stroke scale, but does not differ significantly from G-FAST and CG-FAST. Trial Registration: This study was registered at the Netherlands Trial Register (www.trialregister.nl), NL7387 Funding: BeterKeten collaboration and Theia Foundation (Zilveren Kruis) Declaration of Interests: Diederik Dippel and Aad van der Lugt report funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and unrestricted grants from Penumbra Inc., Stryker, Stryker European Operations BV, Medtronic, Thrombolytic Science, LLC and Cerenovus for research, all paid to institution. Pieter Jan van Doormaal reports funding from Stryker, paid to institution and an unrestricted fee from Bayer. All other authors declare no conflict of interest. Ethics Approval Statement: This study was conducted in accordance with the Dutch Agreement on Medical Treatment Act and the European General Data Protection Regulation. The Institutional Review Board of the Erasmus MC University Medical Centre has reviewed the study protocol and confirmed that the Dutch Medical Research Involving Human Subjects Act is not applicable. Because our study met the exceptions of informed consent regulations, the need for informed consent was waived. Patients or their relatives were informed about the study and could withdraw from the study through an opt-out system.

Rates, risks and routes to reduce vascular dementia (R4vad), a UK-wide multicentre prospective observational cohort study of cognition after stroke: Protocol.

BackgroundStroke commonly affects cognition and, by definition, much vascular dementia follows stroke. However, there are fundamental limitations in our understanding of vascular cognitive impairment, restricting understanding of prevalence, trajectories, mechanisms, prevention, treatment and patient-service needs.AimsRates, Risks and Routes to Reduce Vascular Dementia (R4VaD) is an observational cohort study of post-stroke cognition. We aim to recruit a wide range of patients with stroke, presenting to geographically diverse UK hospitals, into a longitudinal study to determine rates of, and risk factors for, cognitive and related impairments after stroke, to assess potential mechanisms and improve prediction models.MethodsWe will recruit at least 2000 patients within six weeks of stroke with or without capacity to consent and collect baseline demographic, clinical, socioeconomic, lifestyle, cognitive, neuropsychiatric and informant data using streamlined patient-centred methods appropriate to the stage after stroke. We will obtain more detailed assessments at four to eight weeks after the baseline assessment and follow-up by phone and post yearly to at least two years. We will assess diagnostic neuroimaging in all and high-sensitivity inflammatory markers, genetics, blood pressure and diffusion tensor imaging in mechanistic sub-studies.Planned outputs: R4VaD will provide reliable data on long-term cognitive function after stroke, stratified by prior cognition, stroke- and patient-related variables and improved risk prediction. It will create a platform enabling sharing of data, imaging and samples. Participants will be consented for re-contact, facilitating future clinical trials and providing a resource for the stroke and dementia research communities.

BNP for prediction of outcome following lung resection surgery (Profiles); an interim analysis

Introduction Lung cancer is the leading cause of cancer death in the UK with the highest incidence in Scotland. In suitable cases surgical resection is the first-choice treatment; resection rates have risen markedly particularly in elderly patients. Lung cancer surgery is associated with significant co-morbidity resulting in high cardio-respiratory complication rates. B-type natriuretic peptide (BNP) is a quantitative biomarker of myocardial dysfunction, identifying patients at risk of cardiopulmonary complications in a variety of surgeries. Little work has focused on its use for prediction of cardiopulmonary complications following lung resection. The British Thoracic Society (BTS) and The National Institute of Clinical Excellence (NICE) highlight the need for studies concerning patient fitness and operative risk when deciding to undergo lung resection. This analysis explores the predictive role of BNP as a peri-operative biomarker of cardiopulmonary complications following lung resection. Methods With informed consent and ethics approval we prospectively recruited 107 patients undergoing lung resection in a single centre. BNP was measured pre-op (BNPpre-op) and on post-op days 2&3 (BNPpost-op). Association was sought between peri-operative BNP levels and cardiopulmonary complications (according to the European Society of Thoracic Surgeons definitions) and hospital length of stay. Friedman's test, Mann-Whitney U-test and Spearman's rank test were used as appropriate. Results BNP increased post-operatively, peaking on POD2, (p Discussion This study demonstrates association between peri-operative BNP levels and post-operative, in-hospital, cardio-pulmonary complications highlighting the potential for BNP as a predictive marker in patients undergoing lung resection. Further work is required to identify association between peri-operative BNP and longer-term complications and to explore the integration of BNP into risk prediction models for patients undergoing lung resection surgery. In previous pilot work, Pre-op BNP was associated with breathlessness 3-months postoperatively1. PROFILES is a multicentre prospective observational cohort study of 250 patients (across four sites in Scotland and Northern Ireland) undergoing lung resection and seeks to validate this finding (NCT03888937). Upon completion of recruitment we hope to create a novel scoring tool incorporating BNP, to identify those at risk of disabling dyspnoea.

Pancreatic Cancer Malnutrition and Pancreatic Exocrine Insufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer

Background: Malnutrition and cachexia are common in patients with advanced pancreatic ductal adenocarcinoma (PDAC) and have a significant influence on the tolerance and response to treatments. If timely identified, malnourished PDAC patients could be treated to increase their capacity to complete the planned treatments and, therefore, possibly, improve their efficacy.Aims: The aim of this study is to assess the impact of nutritional status, pancreatic exocrine insufficiency (PEI), and other clinical factors on patient outcomes in patients with advanced PDAC.Methods: PAncreatic Cancer MAlnutrition and Pancreatic Exocrine INsufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer (PAC-MAIN) is an international multicenter prospective observational cohort study. The nutritional status will be determined by means of Mini-Nutritional Assessment score and laboratory blood tests. PEI will be defined by reduced fecal elastase levels. Main outcome: adherence to planned chemotherapy in the first 12 weeks following the diagnosis, according to patients' baseline nutritional status and quantified and reported as “percent of standard chemotherapy dose delivered.” Secondary outcomes: rate of chemotherapy-related toxicity, progression-free survival, survival at 6 months, overall survival, quality of life, and the number of hospitalizations. Analysis: chemotherapy dosing over the first 12 weeks of therapy (i.e., percent of chemotherapy received in the first 12 weeks, as defined above) will be compared between well-nourished and malnourished patients. Sample size: based on an expected percentage of chemotherapy delivered of 70% in well-nourished patients, with a type I error of 0.05 and a type II error of 0.20, a sample size of 93 patients per group will be required in case of a percentage difference of chemotherapy delivered of 20% between well-nourished and malnourished patients, 163 patients per group in case of a difference of 15% between the groups, and 356 patients per group in case of a 10% difference. Centers from Russia, Romania, Turkey, Spain, Serbia, and Italy will participate in the study upon Local Ethics Committee approval.Discussion: PAC-MAIN will provide insights into the role of malnutrition and PEI in the outcomes of PDAC. The study protocol was registered at clinicaltrials.gov as NCT04112836.