Hyperacute prediction of functional outcome in spontaneous intracerebral haemorrhage: systematic review and meta-analysis

Purpose To describe the association between factors routinely available in hyperacute care of spontaneous intracerebral haemorrhage (ICH) patients and functional outcome. Methods We searched Medline, Embase and CINAHL in February 2020 for original studies reporting associations between markers available within six hours of arrival in hospital and modified Rankin Scale (mRS) at least 6 weeks post-ICH. A random-effects meta-analysis was performed where three or more studies were included. Findings Thirty studies were included describing 40 markers. Ten markers underwent meta-analysis and age (OR = 1.06; 95%CI = 1.05 to 1.06; p < 0.001), pre-morbid dependence (mRS, OR = 1.73; 95%CI = 1.52 to 1.96; p < 0.001), level of consciousness (Glasgow Coma Scale, OR = 0.82; 95%CI = 0.76 to 0.88; p < 0.001), stroke severity (National Institutes of Health Stroke Scale, OR=1.19; 95%CI = 1.13 to 1.25; p < 0.001), haematoma volume (OR = 1.12; 95%CI=1.07 to 1.16; p < 0.001), intraventricular haemorrhage (OR = 2.05; 95%CI = 1.68 to 2.51; p < 0.001) and deep (vs. lobar) location (OR = 2.64; 95%CI = 1.65 to 4.24; p < 0.001) were predictive of outcome but systolic blood pressure, CT hypodensities and infratentorial location were not. Of the remaining markers, sex, medical history (diabetes, hypertension, prior stroke), prior statin, prior antiplatelet, admission blood results (glucose, cholesterol, estimated glomerular filtration rate) and other imaging features (midline shift, spot sign, sedimentation level, irregular haematoma shape, ultraearly haematoma growth, Graeb score and onset to CT time) were associated with outcome. Conclusion Multiple demographic, pre-morbid, clinical, imaging and laboratory factors should all be considered when prognosticating in hyperacute ICH. Incorporating these in to accurate and precise models will help to ensure appropriate levels of care for individual patients.


Rationale
3 Describe the rationale for the review in the context of what is already known. 3 Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

METHODS
Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number. 4 Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale. 4 Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched. 4 Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated. 4 Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

Risk of bias across studies
15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies). ?
Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

Study selection
17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

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Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

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Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12). 6 Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.
Synthesis of results 21 Present results of each meta-analysis done, including confidence intervals and measures of consistency.
Risk of bias across studies 22 Present results of any assessment of risk of bias across studies (see Item 15). ?
Additional analysis 23 Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

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Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made. 4

Risk of bias in individual studies
12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

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Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means). 5 Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I 2 ) for each meta-analysis.

DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).
Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

Conclusions
26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.

Funding 27
Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.