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Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography. In a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known. Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07). In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials. UK Medical Research Council and British Heart Foundation.

ObjectiveTo summarise evidence of the effects of blood pressure (BP)-lowering interventions after acute spontaneous intracerebral haemorrhage (ICH).MethodsA prespecified systematic review of the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE databases from inception to 23 June 2020 to identify randomised controlled trials that compared active BP-lowering agents versus placebo or intensive versus guideline BP-lowering targets for adults <7 days after ICH onset. The primary outcome was function (distribution of scores on the modified Rankin scale) 90 days after randomisation. Radiological outcomes were absolute (>6 mL) and proportional (>33%) haematoma growth at 24 hours. Meta-analysis used a one-stage approach, adjusted using generalised linear mixed models with prespecified covariables and trial as a random effect.ResultsOf 7094 studies identified, 50 trials involving 11 494 patients were eligible and 16 (32.0%) shared patient-level data from 6221 (54.1%) patients (mean age 64.2 [SD 12.9], 2266 [36.4%] females) with a median time from symptom onset to randomisation of 3.8 hours (IQR 2.6–5.3). Active/intensive BP-lowering interventions had no effect on the primary outcome compared with placebo/guideline treatment (adjusted OR for unfavourable shift in modified Rankin scale scores: 0.97, 95% CI 0.88 to 1.06; p=0.50), but there was significant heterogeneity by strategy (pinteraction=0.031) and agent (pinteraction<0.0001). Active/intensive BP-lowering interventions clearly reduced absolute (>6 ml, adjusted OR 0.75, 95%CI 0.60 to 0.92; p=0.0077) and relative (≥33%, adjusted OR 0.82, 95%CI 0.68 to 0.99; p=0.034) haematoma growth.InterpretationOverall, a broad range of interventions to lower BP within 7 days of ICH onset had no overall benefit on functional recovery, despite reducing bleeding. The treatment effect appeared to vary according to strategy and agent.PROSPERO registration numberCRD42019141136.

Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3–6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI). We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3–6 h after onset of ischaemic stroke. PWI and DWI were done before and 3–5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537. We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71·6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1·24 with alteplase and 1·78 with placebo (ratio 0·69, 95% CI 0·38–1·28; Student's t test p=0·239); the median relative infarct growth was 1·18 with alteplase and 1·79 with placebo (ratio 0·66, 0·36–0·92; Wilcoxon's test p=0·054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0·001), better neurological outcome (p<0·0001), and better functional outcome (p=0·010) than was no reperfusion. Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted. National Health and Medical Research Council, Australia; National Stroke Foundation, Australia; Heart Foundation of Australia.

Mobile Stroke Unit (MSU) expedites the delivery of intravenous thrombolysis in acute stroke patients. We further evaluated the functional outcome of patients shipped to a tertiary care centre or repatriated to local hospitals after triage by MSU in acute stroke syndrome in rural northern Alberta. Consecutive patients with suspected acute stroke syndrome were included. On the basis of neurology consultation and, Computed Tomography findings, patients, who were thrombolysed or needed advanced care were transported to the Comprehensive stroke center (CSC) (Triage to CSC group). Other patients were repatriated to local hospital care (Triage to LHC group). A total of 156 patients were assessed in MSU, 73 (46.8%) were female and the mean age was 66.6 ± 15 years. One hundred and eight (69.2%) patients, including 41 (26.3%) treated with thrombolysis were transported to the CSC (Triage to CSC group) and 48 (30.8%) were repatriated to local hospital care. The diagnosis made in MSU and final diagnosis were matching in 88% (95) and 91.7% (44, p = 0.39) in Triage to CSC and Triage to LHC groups respectively. Prehospital triage by MSU of acute stroke syndrome can reliably repatriate patients to the home hospital. The proposed model has the potential to triage patients according to their medical needs by enabling treatment in home hospitals whenever reasonable.

Clot retraction in intracerebral hemorrhage (ICH) has been described and postulated to be related to effective hemostasis and perihematoma edema (PHE) formation. The incidence and quantitative extent of hematoma retraction (HR) is unknown. Our aim was to determine the incidence of HR between baseline and time of admission. We also tested the hypothesis that patients with HR had higher PHE volume and good prognosis. This was a retrospective single-centre study in which serial planimetric volume measurements of the total hematoma volume (parenchymal (IPH) and intraventricular (IVH)) and PHE were performed in ICH patients with baseline non-contrast computed tomography (CT) completed within 6 hours of onset and follow-up CT 24 (±12) hours from symptom onset. HR was defined as a decrease in volume of >3ml or >15%, and hematoma expansion (HE) as an increase of >6ml or >30%. All other patients were categorized as stable hematoma (HS). Good outcome was defined as modified Rankin Scale (mRS) 0-2 at 90 days. A total of 136 patients (mean age = 69.3±13.39 years, 58.1% male) were included. Median (interquartile range) baseline total hematoma volume was 14.96 (7.80, 31.88) ml. HR >3ml and >15% occurred in 6 (4.4%) and 8 (5.9%) patients, respectively. Neither definition of HR was associated with follow-up PHE (p>0.297) or good outcome (p>0.249). IVH was the only independent predictor of HR (p<0.0241). Early HR is rare and associated with IVH, but not with PHE or clinical outcome. There was no relationship between HR, PHE, and patient prognosis. Therefore, HR is unlikely to be a useful endpoint in clinical ICH studies.

Couples make joint decisions for their shared travels. However, how such decisions are made, i.e., how different perceptions among two individuals interact and influence one another’s decision-making remains less studied. Conventionally, tourists’ decision-making literature were driven by an individual perspective, assuming one person’s decision is made through his or her own perceptions, beliefs, emotions, and past experiences. Among the prevalent decision-making theories, Ajzen (1991)’s Theory of Planned Behavior is among the most widely adopted. The theory posits that a person’s behavioral decision is subject to his or her Attitude toward the target behavior (Att), Subjective Norm (SN), and Perceived Behavioral Control (PBC). However, such individual-focused approach overlooks the influences of the person’s relationship partner, who actively partakes the same decision-making. Couples’ decision-making should be viewed in a dyadic perspective where both intrapersonal and interpersonal mechanisms should be examined. Built upon the theory of Planned Behavior (TPB) and the Actor Partner Independent Model (APIM), this research examines the mutual influence in couple decisionmaking regarding their revisit intentions. Specifically, we posit that both intrapersonal and interpersonal influences of the TPB (attitude, subjective norms, and perceived behavior control) impact on both members’ revisit intentions. The research uses a cross-sectional design with quantitative methods. Dyadic data involving 125 couples (250 individual responses) were collected onsite and analyzed with APIM and structural equation modeling (SEM). Findings suggest that above and beyond the intrapersonal effects of the TPB (Attitude, SN, and PBC), interpersonal effects of TPB predictors also significantly influence revisit intentions. This research contributes to the tourist decision-making literature by extending TPB to dyads and provides a nuanced understanding of how couples make a tourist decision. Practically, our research provides implications for hospitality and tourist service providers in devising their marketing strategies, especially for those who target couple or family customers.

Background: The reasons for worse outcome following ischemic stroke in patients with atrial fibrillation (AF) remain unclear. We aimed to elucidate the pathophysiological determinants of poorer stroke outcome in patients with AF using systematic MRI data from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). Methods: Comparisons of infarct size, hypoperfusion volume, infarct growth, arterial occlusion, recanalization, reperfusion, hemorrhagic transformation and stroke severity were made between patients with and without AF enrolled in the EPITHET study. Results: AF was present in 42 of 101 patients. At baseline, AF patients were older (79 vs. 73 years, p = 0.02), had more severe neurological impairment (National Institutes of Health Stroke Scale score 16 vs. 11, p = 0.006), larger infarcts (29 vs. 15 ml, p = 0.04) and greater volumes of more severe hypoperfusion (T max ≧8 s, perfusion-weighted imaging volume 70 vs. 43 ml, p = 0.01) compared to patients without AF. There were no significant differences in arterial occlusion site, infarct growth, recanalization or reperfusion. At outcome, AF patients had larger infarcts (52 vs. 16 ml, p = 0.05), more severe hemorrhagic transformation (29 vs. 5%, p = 0.002 for parenchymal hematomas), greater disability (modified Rankin Scale score 4 vs. 3, p = 0.03) and higher mortality rates (31 vs. 12%, p = 0.04). AF was an independent predictor of parenchymal hematoma (OR = 6.90, 95% CI = 1.57–30.25), but not mortality (OR = 2.56, 95% CI = 0.83–7.85). Conclusions: Patients with AF have worse clinical and imaging outcomes following ischemic stroke. This study suggests that the adverse effect of AF is due to greater volumes of more severely hypoperfused tissue, leading to larger infarct size and greater risk of severe hemorrhagic transformation.

Purpose The purpose of this paper is to discuss the current status of experimental research within hospitality and tourism. This paper further aims to develop practical ideas for enhancing the adoption of a cause and effect mindset in researchers. Design/methodology/approach A mini-review of the level of experimental designs and best-practice ideas published by the top 12 journals in hospitality and tourism over a five-year period was conducted. Findings Although the absolute number of experimental studies is growing, the ratio of experimental studies to overall publications remains low at 6.4%. To increase the take-up of experimental design, a broader typology of field experiments is presented. Practical steps to increase causal reality are provided under the categories of purpose; scenario development; scenario testing; and sample characteristics. Research limitations/implications The methodological advances suggested in this paper can contribute to more robust theory development and testing. The recommendations offer guidance to a new generation of researchers seeking to add causal value to their studies, researchers collaborating with scholars from other discipline areas and hospitality managers seeking stronger evidence of cause and effect. Originality/value This paper identifies key obstacles to the take-up of experimental design and the contemporary status of experimental design. A novel typology of five experimental designs that distinguish the difference between experimental and correlational designs in terms of explanatory power is presented, together with a comprehensive list of best practice suggestions to increase causal reality in scenario design.

Leukoaraiosis regions may be more vulnerable to decreases in cerebral perfusion. We aimed to assess perfusion in leukoaraiosis regions in acute intracerebral hemorrhage (ICH) patients. We tested the hypothesis that aggressive acute BP reduction in ICH patients is associated with hypoperfusion in areas of leukoaraiosis. In the ICH Acutely Decreasing Arterial Pressure Trial (ICH ADAPT), patients with ICH <24 hours duration were randomized to two systolic BP (SBP) target groups (<150 mmHg vs. <180 mmHg). Computed tomography perfusion (CTP) imaging was performed 2h post-randomization. Leukoaraiosis tissue volumes were planimetrically measured using semi-automated threshold techniques on the acute non-contrast CT. CTP source leukoaraiosis region-of-interest object maps were co-registered with CTP post-processed maps to assess cerebral perfusion in these areas. Seventy-one patients were included with a mean age of 69±11.4 years, 52 of whom had leukoaraiosis. The mean relative Tmax (rTmax) of leukoaraiotic tissue (2.3±2s) was prolonged compared to that of normal appearing white matter in patients without leukoaraiosis (1.1±1.2s, p = 0.04). In the 52 patients with leukoaraiosis, SBP in the aggressive treatment group (145±20.4 mmHg, n = 27) was significantly lower than that in the conservative group (159.9±13.1 mmHg, n = 25, p = 0.001) at the time of CTP. Despite this SBP difference, mean leukoaraiosis rTmax was similar in the two treatment groups (2.6±2.3 vs. 1.8±1.6 seconds, p = 0.3). Cerebral perfusion in tissue affected by leukoaraiosis is hypoperfused in acute ICH patients. Aggressive BP reduction does not appear to acutely aggravate cerebral hypoperfusion.

The use of multimodal computed tomography imaging (MMCT) in routine clinical assessment of stroke patients improves the identification of patients with large regions of salvageable brain tissue, lower risk for haemorrhagic transformation, or a large vessel occlusion requiring endovascular therapy. To evaluate the cost-effectiveness of using MMCT compared to usual practice for determining eligibility for reperfusion therapy with alteplase using real world data from the International Stroke Perfusion Imaging Registry (INSPIRE). We performed a cost-utility analysis. Mean costs and quality-adjusted life years (QALYs) per patient for two alternative screening protocols were calculated. Protocol 1 represented usual practice, while Protocol 2 reflected treatment targeting using multimodal imaging. Cost-effectiveness was assessed using the net-benefit framework. Protocol 1 had a total mean per patient cost of $2,013 USD and 0.148 QALYs. Protocol 2 had a total mean per patient cost of $1,519 USD and 0.153 QALYs. For a range of willingness-to-pay values, representing implicit thresholds of cost-effectiveness, the lower bound of the incremental net monetary benefit statistic was consistently greater than zero, indicating that MMCT is cost- effective compared to usual practice. The results were most sensitive to variation in the mean number of alteplase vials administered. In a healthcare setting where multimodal imaging technologies are available and reimbursed, their use in screening patients presenting with acute stroke to determine eligibility for alteplase treatment is cost-effective given a range of willingness-to-pay thresholds and warrants consideration as an alternative to routine practice.