To report an updated, systematic review of medical literature from January 2003 to July 2008, on endovascular treatment (EVT) of intracranial unruptured aneurysms (UAs) (a) to assess the morbidity ...and case fatality rate of EVT of UAs, (b) to understand how bias can affect results, and (c) to estimate the efficacy of EVT by using reported digital subtraction angiographic (DSA) results and clinical follow-up events.
This article was prepared in accordance with the Meta-Analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The literature was searched by using PubMed and the EMBASE and Cochrane Library databases. Eligibility criteria were (a) explicit procedural mortality and morbidity rates; (b) at least 10 patients; (c) saccular, intradural, nondissecting UAs; (d) original study published in English or French between January 2003 and July 2008; and (e) a methodological quality score higher than 6, according to Strengthening the Reporting of Observational Studies in Epidemiology criteria. End points included procedural mortality and morbidity, defined as a modified Rankin scale score of 3-6 at 1 month, and efficacy, estimated by using immediate and follow-up digital subtraction angiographic results, as well as delayed hemorrhagic events.
Seventy-one studies were included. Procedural unfavorable outcome was found in 4.8% (random-effect weighted average; 189 of 5044) of patients (99% confidence interval CI: 3.9%, 6.0%). Immediate angiographic results showed satisfactory occlusion in 86.1% (2660 of 3089) of UAs. Recurrences were shown in 321 (24.4%) of 1316 patients followed up for 0.4-3.2 years. Retreatment was performed in 9.1% (random-effect weighted average; 166 of 1699) of patients (99% CI: 6.2%, 13.1%). The annual risk of bleeding after EVT was 0.2% (random-effect weighted average; nine of 1395) of patients (99% CI: 0.1%, 0.3%), but clinical follow-up was short, limited to the first 6 months for 76.7% (n = 1071) of reported patients.
EVT of UAs can be performed with relative safety. The efficacy of treatment as compared with observation has not been rigorously documented.
Pre-hospital identification of key subgroups within the suspected stroke population could reduce delays to emergency treatment. We aimed to identify and describe technology with existing proof of ...concept for diagnosis or stratification of patients in the pre-hospital setting.
A systematic electronic search of published literature (from 01/01/2000 to 06/06/2019) was conducted in five bibliographic databases. Two reviewers independently assessed eligibility of studies or study protocols describing diagnostic/stratification tests (portable imaging/biomarkers) or technology facilitating diagnosis/stratification (telemedicine) used by ambulance personnel during the assessment of suspected stroke. Eligible descriptions required use of tests or technology during the actual assessment of suspected stroke to provide information directly to ambulance personnel in the pre-hospital setting. Due to study, intervention and setting heterogeneity there was no attempt at meta-analysis.
2887 articles were screened for eligibility, 19 of which were retained. Blood biomarker studies (n = 2) were protocols of prospective diagnostic accuracy studies, one examining purines and the other a panel of known and novel biomarkers for identifying stroke sub-types (versus mimic). No data were yet available on diagnostic accuracy or patient health outcomes. Portable imaging studies (n = 2) reported that an infrared screening device for detecting haemorrhages yielded moderate sensitivity and poor specificity in a small study, whilst a dry-EEG study to detect large vessel occlusion in ischaemic stroke has not yet reported results. Fifteen evaluations of pre-hospital telemedicine were identified (12 observational and 3 controlled comparisons) which all involved transmission of stroke assessment data from the pre-hospital setting to the hospital. Diagnosis was generally comparable with hospital diagnosis and most telemedicine systems reduced time-to-treatment; however, it is unknown whether this time saving translated into more favourable clinical outcomes. Telemedicine systems were deemed acceptable by clinicians.
Pre-hospital technologies to identify clinically important subgroups amongst the suspected stroke population are in development but insufficient evidence precludes recommendations about routine use in the pre-hospital setting. Multi-centre diagnostic accuracy studies and clinical utility trials combining promising technologies are warranted.
Age and infarct volume are strong predictors of outcome in patients with ischemic stroke who underwent endovascular therapy (EVT). We aimed to investigate the impact of ischemic core volume (ICV) on ...stroke outcome after EVT in elderly.
Using the HERMES (Highly Effective Reperfusion Using Multiple Endovascular Devices) collaboration, a patient-level meta-analysis of 7 randomized trials in which patients were enrolled from December 2010 to April 2015) dataset, we categorized patients into those aged <75 and ≥75 years. ICV was calculated on computed tomography perfusion or magnetic resonance diffusion-weighted imaging. The association between ICV and the benefit of EVT over best medical treatment on outcome (modified Rankin Scale mRS at 90 days) and an ICV threshold for high likelihood (≥90%) of very poor outcome (mRS score ≥5) after EVT were investigated.
A total of 899 patients who had baseline ICV data, 247 patients aged ≥75 years, of which 118 were randomized in the EVT arm. Patients aged ≥75 years required smaller ICV to achieve mRS score ≤3 than those aged <75 years in the EVT arm (median 10.7 mL versus 23.9 mL,
<0.001). In patients aged ≥75 years, modeling of outcome in both treatment arms revealed potential loss of effect for EVT at ICV of ≥50 mL or ≥85 mL for achieving mRS score ≤3 or ≤4, respectively. Treatment effect of EVT was significant in ICV <50 mL for mRS ≤3 (odds ratio 2.38, 95% confidence interval 1.35-4.22). ICV ≥132 mL was a threshold for high likelihood of very poor outcome after EVT. However, EVT still predicted at least 30% rate of mRS ≤3 at 150 mL ICV if near-complete or complete reperfusion was achieved.
Baseline ICV has an impact on stroke outcome after EVT in the elderly, but elderly patients with large ICV may still benefit from EVT if near-complete or complete reperfusion is achieved. Young patients seem to benefit from EVT regardless of ICV status.
Current guidelines for ischaemic stroke treatment recommend a strict, but arbitrary, upper threshold of 185/110 mm Hg for blood pressure before endovascular thrombectomy. Nevertheless, whether ...admission blood pressure influences the effect of endovascular thrombectomy on outcome remains unknown. Our aim was to study the influence of admission systolic blood pressure (SBP) on functional outcome and on the effect of endovascular thrombectomy.
We used individual patient data from seven randomised controlled trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, PISTE, and THRACE) that randomly assigned patients with anterior circulation ischaemic stroke to endovascular thrombectomy (predominantly using stent retrievers) or standard medical therapy (control) between June 1, 2010, and April 30, 2015. We included all patients for whom SBP data were available at hospital admission. The primary outcome was functional outcome (modified Rankin Scale) at 90 days. We assessed the association of SBP with outcome in both the endovascular thrombectomy group and the control group using multilevel regression analysis and tested for non-linearity and for interaction between SBP and effect of endovascular thrombectomy, taking into account treatment with intravenous thrombolysis.
We included 1753 patients (867 assigned to endovascular thrombectomy, 886 assigned to control) after excluding 11 patients for whom SBP data were missing. We found a non-linear association between SBP and functional outcome with an inflection point at 140 mm Hg (732 42% of 1753 patients had SBP <140 mm Hg and 1021 58% had SBP ≥140 mm Hg). Among patients with SBP of 140 mm Hg or higher, admission SBP was associated with worse functional outcome (adjusted common odds ratio acOR 0·86 per 10 mm Hg SBP increase; 95% CI 0·81–0·91). We found no association between SBP and functional outcome in patients with SBP less than 140 mm Hg (acOR 0·97 per 10 mm Hg SBP decrease, 95% CI 0·88–1·05). There was no significant interaction between SBP and effect of endovascular thrombectomy on functional outcome (p=0·96).
In our meta-analysis, high admission SBP was associated with worse functional outcome after stroke, but SBP did not seem to negate the effect of endovascular thrombectomy. This finding suggests that admission SBP should not form the basis for decisions to withhold or delay endovascular thrombectomy for ischaemic stroke, but randomised trials are needed to further investigate this possibility.
Medtronic.
NLRP1 is an innate immune sensor that can form cytoplasmic inflammasome complexes. Polymorphisms in NLRP1 are linked to asthma; however, there is currently no functional or mechanistic explanation ...for this.
We sought to clarify the role of NLRP1 in asthma pathogenesis.
Results from the GALA II cohort study were used to identify a link between NLRP1 and asthma in Mexican Americans. In vitro and in vivo models for NLRP1 activation were applied to investigate the role of this inflammasome in asthma at the molecular level.
We document the association of an NLRP1 haplotype with asthma for which the single nucleotide polymorphism rs11651270 (M1184V) individually is the most significant. Surprisingly, M1184V increases NLRP1 activation in the context of N-terminal destabilization, but decreases NLRP1 activation on dipeptidyl peptidase 9 inhibition. In vitro studies demonstrate that M1184V increases binding to dipeptidyl peptidase 9, which can account for its inhibitory role in this context. In addition, in vivo data from a mouse model of airway inflammation reveal a protective role for NLRP1 inflammasome activation reducing eosinophilia in this setting.
Linking our in vitro and in vivo results, we found that the NLRP1 variant M1184V reduces inflammasome activation in the context of dipeptidyl peptidase 9 inhibition and could thereby increase asthma severity. Our studies may have implications for the treatment of asthma in patients carrying this variant of NLRP1.
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The clinical efficacy and cost-effectiveness of mechanical thrombectomy (MT) for the treatment of large vessel occlusion stroke is well established, but uncertainty remains around the true cost of ...delivering this treatment within the NHS. The aim of this study was to establish the cost of providing MT within the hyperacute phase of care and to explore differences in resources used and costs across different neuroscience centres in the UK.
This was a multicentre retrospective study using micro-costing methods to enable a precise assessment of the costs of MT from an NHS perspective. Data on resources used and their costs were collected from five UK neuroscience centres between 2015 and 2018.
Data were collected on 310 patients with acute ischaemic stroke treated with MT. The mean total cost of providing MT and inpatient care within 24 hours was £10,846 (95% confidence interval (CI) 10,527–11,165) per patient. The main driver of cost was MT procedure costs, accounting for 73% (£7,943; 95% CI 7,649–8,237) of the total 24-hour cost. Costs were higher for patients treated under general anaesthesia (£11,048; standard deviation (SD) 2,654) than for local anaesthesia (£9,978; SD 2,654), mean difference £1,070 (95% CI 381–1,759; p=0.003); admission to an intensive care unit (ICU; £12,212; SD 3,028) against for admission elsewhere (£10,179; SD 2,415), mean difference £2,032 (95% CI 1,345–2,719; p<0001).
The mean cost within 72 hours was £12,440 (95% CI 10,628–14,252). The total costs for the duration of inpatient care before discharge from a thrombectomy centre was £14,362 (95% CI 13,603–15,122).
Major factors contributing to costs of MT for stroke include consumables and staff for intervention, use of general anaesthesia and ICU admissions. These findings can inform the reimbursement, provision and strategic planning of stroke services and aid future economic evaluations.
•Cases with and without epilepsy were linked with anonymised primary care data.•Primary care diagnosis and drug codes accurately identify the cases with epilepsy.•Drug codes alone can be used to ...identify children with epilepsy.•Combining drug and diagnosis codes for adults and children increases accuracy.
Anonymised, routinely-collected healthcare data is increasingly being used for epilepsy research. We validated algorithms using general practitioner (GP) primary healthcare records to identify people with epilepsy from anonymised healthcare data within the Secure Anonymised Information Linkage (SAIL) databank in Wales, UK.
A reference population of 150 people with definite epilepsy and 150 people without epilepsy was ascertained from hospital records and linked to records contained within SAIL (containing GP records for 2.4 million people). We used three different algorithms, using combinations of GP epilepsy diagnosis and anti-epileptic drug (AED) prescription codes, to identify the reference population.
Combining diagnosis and AED prescription codes had a sensitivity of 84% (95% ci 77–90) and specificity of 98% (95–100) in identifying people with epilepsy; diagnosis codes alone had a sensitivity of 86% (80–91) and a specificity of 97% (92–99); and AED prescription codes alone achieved a sensitivity of 92% (70–83) and a specificity of 73% (65–80). Using AED codes only was more accurate in children achieving a sensitivity of 88% (75–95) and specificity of 98% (88–100).
GP epilepsy diagnosis and AED prescription codes can be confidently used to identify people with epilepsy using anonymised healthcare records in Wales, UK.
The photochemistry of cyclic carbonate esters proceeds by the photochemical extrusion of carbon dioxide to give 1, 3‐diradicals which produce oxiranes as well as other radical derived species. The ...corresponding cyclic sulfite esters, upon irradiation, give intermediates that are trapped by alcohols yet generate no oxiranes. These results are consistent with ionic intermediates.
People with one or more first degree relative affected (FDRA) by aneurysmal subarachnoid haemorrhage (aSAH) are at a higher lifetime risk of an aSAH than those without a family history. Screening may ...be worthwhile for people with two or more FDRA by aSAH. Little is known about the characteristics of people with a family history of aSAH who undergo screening in clinical practice.
Observational analysis of consecutive attendances at an intracranial aneurysm screening clinic.
Of 96 adults seen, 19 did not have a family history of aSAH and 77 had one or more FDRA by aSAH: 35 had two or more FDRA, 21 had one FDRA plus one or more affected second degree relative and 21 had one FDRA only. In these three respective groups, 29 (83%), 15 (71%) and five (24%) adults underwent screening, of whom six (21%), two (13%) and one (20%) had an aneurysm detected (p=0.5). Of the nine patients with aneurysms, four underwent treatment. Considering other risk factors, adults with two or more FDRA were more likely to be hypertensive (OR 3.3, 95% CI 1.0 to 10.8; p=0.046) but were no more likely to smoke or drink to excess than adults with one FDRA. Adults who underwent screening were more likely to be hypertensive and drink alcohol to excess (both p=0.03), but were no more likely to smoke than those who were not screened.
In clinical practice, people undergoing intracranial aneurysm screening had stronger family histories of aSAH and they were also more likely to have modifiable risk factors for aSAH.
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