1,721,075 research outputs found
RESTART data request form
No full textTo request access to the RESTART dataset, please fill out the data request form. Associated documentation is available in the other datasets belonging to this collection, see https://datashare.is.ed.ac.uk/handle/10283/3265 .
RESTART recruited 537 participants between 22 May 2013 and 31 May 2018. The main results, based on follow-up of these participants until 30 November 2018, are available and were published on 22 May 2019. A plain English summary is available at:www.RESTARTtrial.org.The main results of the trial were published in The Lancet https://doi.org/10.1016/S0140-6736(19)30840-2. The results of the imaging sub-group analyses of the trial were published in The Lancet Neurology https://doi.org/10.1016/S1474-4422(19)30184-X).
Please read this document about planned secondary analyses:
Salman, Rustam Al-Shahi. (2019). RESTART | planned secondary analyses, 2013-2018 [text]. University of Edinburgh. https://doi.org/10.7488/ds/2551
A fully anonymised version of the dataset used for analysis with individual participant data and a data dictionary will be available for other researchers to apply to use 1 year after publication, from 22 May 2020. Written proposals will be assessed by members of the RESTART trial steering committee and a decision made about the appropriateness of the use of data. A data sharing agreement will be put in place before any data are shared. Please read this document about planned data sharing:
Stephen, Jacqueline; Salman, Rustam Al-Shahi. (2020). RESTART Data Sharing, [text]. University of Edinburgh https://doi.org/10.7488/ds/2806
RESTART trial main results dataset
No full textAnalysis dataset used for the RESTART main results and imaging sub-study results papers in 2019Protocol, SAP, data dictionary, sharing dataset, annotated CRF
Edinburgh diagnostic criteria for lobar ICH associated with CAA
No full textSummary of the Edinburgh diagnostic criteria for lobar ICH associated with CAA, illustrative cases, and the diagnostic test accuracy of two cut-pointsPortable Network Graphics, PDF, and PowerPoint image formats for people to use in PowerPoint presentations or manuscripts that describe the Edinburgh diagnostic criteria for lobar intracerebral haemorrhage associated with moderate/severe cerebral amyloid angiopath
RESTART Extended Follow Up Dataset
No full textAnalysis dataset used for the RESTART extended follow up results paper in 2021 (doi:10.1001/jamaneurol.2021.2956). This dataset contains the data dictionary and statistical analysis plan form the RESTART extended follow up. It also contains the Data sharing description and Request form that should be used to obtain a copy of the data. Additional information about the data (trial protocol, annotated CRFs) can be found with the RESTART main results dataset ( https://doi.org/10.1016/S0140-6736(19)30840-2 ).Salman, Rustam Al-Shahi; Rodriguez Carbonell, Aryelly; Stephen, Jacqueline; Drever, Jonathan. (2022). RESTART Extended Follow Up Dataset, [dataset]. University of Edinburgh. Deanery of Clinical Sciences. Centre for Clinical Brain Sciences. https://doi.org/10.7488/ds/3399
Supplemental materials for a systematic review of stereotactic radiosurgery for cerebral cavernous malformations
No full textSupplementary data in support of manuscript: "Stereotactic radiosurgery for cerebral cavernous malformations: a systematic review"
Prevention of venous thromboembolism in acute spontaneous intracerebral haemorrhage: A survey of opinion
Full text linkIntroduction: People immobilized following acute spontaneous intracerebral haemorrhage (ICH) are at risk of venous thromboembolism (VTE) but the role of short-term prophylactic anticoagulation remains uncertain. We surveyed UK clinical practice and opinion regarding preventing VTE after ICH. Patients and methods: An online survey was sent to stroke healthcare professionals within the United Kingdom and Ireland via a professional society (British and Irish Association of Stroke Physicians (BIASP)). Results: One hundred and twenty-three staff members responded to the survey, of whom 80% were consultant stroke physicians. All responders except one considered the issue to be important or extremely important, but only 5 (4%) were “extremely certain” and 51 (41%) “fairly certain” regarding the optimal treatment approach. Intermittent pneumatic compression (IPC) devices alone were the most used method (in 60%) followed by IPC devices and switching to low molecular weight heparin (LMWH) (in 30%). We identified high levels of uncertainty regarding the role of anticoagulation, and its optimal timing; uncertainty was greater in lobar compared to deep ICH. Most respondents (93%) consider a randomised controlled trial investigating the role of pharmacological VTE prophylaxis after acute ICH as important and would consider participation. Discussion and conclusion: The optimal method for the prevention of VTE in non-traumatic ICH patients remains an area of clinical uncertainty. Clinical trials assessing short-term anticoagulation in patients after acute ICH would be beneficial in providing evidence to resolve this clinical dilemma.</p
RESTART Data Sharing
No full textDocumentation addressing the following aspects of data sharing in relation to the RESTART clinical trial results: * overview and data sharing agreement; * process; * anonymisation; * risk of reidentification; * composition of the study data pack; * release.Stephen, Jacqueline; Salman, Rustam Al-Shahi. (2020). RESTART Data Sharing, [text]. University of Edinburgh. College of Medicine & Veterinary Medicine. https://doi.org/10.7488/ds/2806
Modulation of inflammation after brain haemorrhage by myelomononuclear Nrf2
Full text linkSpontaneous intracerebral haemorrhage (ICH) is associated with substantial morbidity and mortality. Randomised trials of treatments to reduce haematoma volumes have not demonstrated efficacy. Nrf2 is a transcription factor that responds to oxidative stress by inducing antioxidant gene expression. Perihaematomal oedema (PHO) after ICH may reflect modifiable processes of inflammation and secondary injury. In a prospective, community-based ICH inception cohort, I found that early PHO was not associated with death or dependency, independent of haematoma volume. Because later PHO has been associated with poor outcome, this indicates a window where the link between oedema and outcome is not yet established. After systematically identifying all published studies of molecular measures of inflammation in patient brain tissue after ICH, I performed a meta-analysis which established that the proinflammatory cytokine interleukin-1β is increased within 6h of ICH onset. However, meta-analysis of other measures of inflammation was not possible because of limited replication and poor reporting. I therefore compared brain transcriptomes from patients who died after ICH with those who died suddenly of non-neurological disease using bulk RNA sequencing and dual in situ RNA hybridisation-immunohistochemistry (IHC).
Genes which are specifically expressed by myeloid cells or astrocytes were increased after ICH and coexpressed with Nrf2 target genes. I modelled ICH in mice using striatal bacterial collagenase injection and conditionally deleted myelomononuclear Nrf2 using cre-mediated excision. I used grip strength assessment, IHC and bulk RNA sequencing of sorted myelomononuclear cells and found that myelomononuclear Nrf2 is protective and facilitates cell autonomous adaptive responses to ICH whilst suppressing interferon stimulated gene expression. In co-cultured primary microglia, astrocytes, and neurons, I confirmed that microglial Nrf2 activation facilitates adaptive microglial transcriptional responses to blood clot conditioned media and blunts lipopolysaccharide-induced astrocytosis. Myelomononuclear Nrf2 is therefore a tractable therapeutic target for ICH. Future work should dissect specific roles and protective mechanisms of downstream Nrf2-regulated responses to ICH
Blood pressure variability and the characteristics and outcomes of patients with intracerebral haemorrhage
Full text linkHigh blood pressure (BP) is the strongest modifiable risk factor for spontaneous
intracerebral haemorrhage (ICH). International guidelines about the management of
high BP for primary prevention of cardiovascular disease and secondary prevention
after stroke refer to mean or 'usual' BP targets for office BP monitoring (long-term
visit-to-visit BP). Yet, there is mounting evidence that higher systolic BP variability
(SBPV) is associated with incident cardiovascular disease and poor outcomes after
ICH.
In this thesis, I aimed to address three areas of uncertainty regarding the associations
between SBPV and the characteristics and outcomes of patients with ICH:
Question 1: Is long-term visit-to-visit SBPV before ICH associated with the
characteristics of patients with incident, first-ever ICH?
In the days leading up to ICH, one population-based study showed that SBP was
significantly higher than average pre-morbid SBP, suggesting higher SBP levels/
higher SBPV may trigger the event. However, these findings have not been
replicated in another methodologically rigorous population-based study.
My
systematic review did not identify any studies that assessed associations between
long-term visit-to-visit SBPV before ICH onset and the characteristics of patients
with ICH at diagnosis.
I analysed data from the Lothian Audit of the Treatment of Cerebral Haemorrhage
(LATCH), a prospective population-based study that identified adults with first-ever
ICH between 1st June 2010 and 31st May 2013, inclusive, and the nested Lothian
IntraCerebral Haemorrhage, Pathology, Imaging and Neurological Outcome
(LINCHPIN) sub-study. I did not detect a relationship between higher SBP levels or
higher SBPV during ten years before ICH and increasing temporal proximity to the
time of ICH onset. Compared to patients with lower long-term visit-to-visit SBPV
during ten years before ICH, patients with higher long-term visit-to-visit SBPV were
more likely to have a premorbid diagnosis of hypertension, higher BP at ICH
diagnosis, and evidence of greater cerebral small vessel disease (CVSD) burden on
diagnostic CT brain scan. They were less likely to have CT brain characteristics that
predicted the presence of cerebral amyloid angiopathy (CAA)-associated ICH in the
cohort. However, after accounting for confounding factors, there were no clear and
consistent associations between the degree of long-term visit-to-visit SBPV during
ten years before ICH and greater CVSD burden on diagnostic CT brain scan, ICH
location or the severity of underlying CAA on research autopsy. My analyses were
limited by poor BP data availability, and future research may benefit from harnessing
the power of electronic data linkage with primary care records.
Question 2: Are short- and mid-term SBPV after acute ICH associated with clinical
outcomes, independently of important confounding factors?
My systematic review and meta-analysis showed that short- and mid-term SBPV
after acute ICH were associated with poor medium-term (90-day) functional
outcome. However, only 3 of 6 included studies accounted for confounding from
mean SBP, and none accounted for the characteristics of BP-lowering interventions
after acute ICH. Furthermore, evidence about the associations between short- and
mid-term SBPV and other important outcomes after acute ICH was limited.
I led analyses of pooled patient-level data from 3829 participants from two
randomised controlled trials (RCTs) of early, intensive BP lowering after acute ICH
(INTERACT2 and ATACH-II). I showed that higher short-term SBPV during 1-24
hours of BP-lowering treatment after acute ICH (<6 h of onset) was associated with
poorer medium-term functional outcome, greater odds of haematoma growth and
early neurological deterioration within 24 hours, and greater odds of death and
serious adverse events within 90 days. These associations existed independently of
other summary measures of SBP control and important confounders.
In a broader meta-analysis of 6221 patients from 16 RCTs participating in the Blood
pressure in Acute Stroke Collaboration (BASC), I showed that higher short- (1-24
hours) and mid-term (2-7 days) SBPV after acute ICH were associated with poorer
medium-term (90-180 days) functional outcome. However, these associations varied
according to the manner in which BP was lowered. The associations between higher
short-term SBPV during 1-24 h after acute ICH and poorer medium-term function
were strongest amongst patients who received titrated target-based BP lowering with
intravenous α- and β-adrenoreceptor blockers and calcium channel blockers, and
amongst patients who had their BP measured more frequently, and had larger
reductions in their SBP and lower average SBP. The associations between higher
mid-term SBPV during 2-7 days after acute ICH and poorer medium-term function
were strongest amongst patients who were older, had lower baseline SBP, and were
randomised later after symptom onset.
These findings suggest that careful and sustained reductions in SBP may be
beneficial after acute ICH. Future research that aims to test the effects of minimising
short- and mid-term SBPV after acute ICH is required to make definite conclusions
but is likely to require a very large sample size and be prone to various
methodological issues.
Question 3: Is it feasible to assess the associations between long-term visit-to-visit
SBPV and long-term outcomes in survivors of ICH?
My systematic review identified only one study that reported an association between
higher long-term visit-to-visit SBPV after ICH and greater risk of recurrent ICH. The
associations between long-term visit-to-visit SBPV after ICH and other serious
symptomatic vascular events are unknown.
My assessment of data available about long-term visit-to-visit SBPV during 7-365
days after ICH and long-term (>1 year after ICH) outcome in three prospective,
population-based cohorts of ICH indicated that pre-planned analyses were
unfeasible. I made this decision due to a combination of poor 1-year survival and
poor BP data availability. Amongst patients with incident, first-ever ICH in Lothian,
Scotland during 2019, half were eligible for long-term BP lowering after ICH. Yet,
as few as 1 in 10 patients were eligible for activities that involved intensification of
their long-term BP-lowering treatment and frequent BP monitoring. The majority of
patients were excluded due to death and poor prognosis. Improvements in the longterm management of BP in NHS Lothian between 2010-12 and 2019 also
contributed; several patients had systolic BP levels <130 mm Hg, which excluded
them from the studies. My findings highlight complexities to generating evidence
about interventions for secondary prevention of stroke and other serious symptomatic
vascular events after ICH; future research may benefit from prospective, standardised
BP data collection and broader recruitment strategies.
In summary, there were no clear and consistent associations between long-term visitto-visit SBPV before ICH and the characteristics of patients with ICH at diagnosis.
After acute ICH, higher short- and mid-term SBPV were associated with poor
outcomes. Patients who receive titrated target-based BP-lowering interventions may
benefit from careful, sustained reductions in their BP during the first week of
treatment. Analyses of the associations between long-term visit-to-visit SBPV after
ICH and long-term outcomes were unfeasible. Generating definitive evidence about
the effects of reducing SBPV to improve outcomes after ICH is likely to require a
very large sample size and be hampered by various methodological issues
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