online supplement - journal of neurology, neurosurgery
TRANSCRIPT
Online Supplement
Title: Meta-analysis of Timing of Endovascular Aneurysm Treatment in Subarachnoid Haemorrhage: Treatment Within 1-Day May Reduce Poor
Outcome, However Results Inconsistent
Authors:
Sapna Rawal, MD. Division of Neuroradiology, Joint Department of Medical Imaging, Toronto Western Hospital, University Health Network;
Institute of Health Policy, Management and Evaluation; University of Toronto (Toronto, Canada).
Paula Alcaide-Leon, MD. Division of Neuroradiology, Department of Medical Imaging, St. Michael’s Hospital; University of Toronto (Toronto,
Canada)
R. Loch Macdonald, MD. Division of Neurosurgery, St. Michael’s Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma
Research, Keenan Research Centre for Biomedical Research and Li Ka Shing Knowledge Institute, Department of Surgery; University of Toronto
(Toronto, Canada)
Gabriel J. E. Rinkel, MD, FRCPE. Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center
(Utrecht, The Netherlands)
J. Charles Victor, MSc. Institute for Clinical Evaluative Sciences; Institute of Health Policy, Management and Evaluation, University of Toronto
(Toronto, Ontario).
Timo Krings, MD, PhD. Division of Neuroradiology, Joint Department of Medical Imaging, Toronto Western Hospital, University Health
Network; University of Toronto (Toronto, Canada).
Moira K. Kapral, MD. Division of General Internal Medicine and Toronto General Research Institute, Department of Medicine, University
Health Network; Institute for Clinical Evaluative Sciences; Department of Medicine and Institute of Health Policy, Management and Evaluation,
University of Toronto (Toronto, Ontario).
Andreas Laupacis, MD. Department of Medicine, St. Michael's Hospital, Li Ka Shing Knowledge Institute, Institute for Clinical Evaluative
Sciences; Institute of Health Policy, Management and Evaluation, University of Toronto (Toronto, Ontario).
Online Supplement Contents: Table I: Risk of bias grading criteria based on Newcastle-Ottawa Scale
Table II: Risk of bias grading score based on Newcastle-Ottawa Scale
Table III: Timing categorization of included studies
Table IV: Poor outcome – distribution of confounders (poor grade SAH and age) in early versus late treatment groups
Table V: Case fatality – distribution of confounders (poor grade SAH and age) in early versus late treatment groups
Figure I: Funnel Plot – Poor Outcome
Figure II: Funnel Plot – Case Fatality
Appendix: Search Strategy
Table I: Risk of bias grading criteria based on Newcastle-Ottawa Scale
Reference: Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for
assessing the quality of nonrandomised studies in meta-analyses. (Accessed July 5, 2016, at
http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.)
Categories Details Points
Selection
Representativeness of the exposed cohort
Documented SAH of aneurysmal source treated by endovascular coiling as the primary treatment modality,
without other restrictive selection criteria 1
Selection of the non exposed cohort Documented that treatment delay not due to clinical decision to delay treatment 1
Ascertainment of exposure Time to treatment defined as time from SAH ictus to treatment 1
Demonstration that outcome of interest was not present at
start of study Outcome (poor functional status/mortality) not present at baseline 1
Comparability
Comparability of cohorts on the basis of the design or
analysis
Baseline / pre-treatment neurologic status (good vs poor) similarly distributed between early and late
timing groups (statistical testing) 1
Age similar between early and late timing groups (statistical testing) 1
Outcome
Assessment of outcome Blinded / objectively reported, not survey or self-report 1
Was follow-up long enough for outcomes to occur? 6 months for poor functional outcome/mortality 1
Adequacy of follow up of cohorts loss to follow-up <10% 1
TOTAL 9
Table II: Risk of bias grading score (based on Newcastle-Ottawa Scale)
Study Selection
(4)
Comparability
(2)
Outcome
(3)
Total
(9) Notes
ApSimon
1998 2 1 1 4
In early part of study, only failed or high surgical risk aneurysms treated with coiling; uncertainty regarding
treatment delay, distribution of age unknown, short follow-up from unclear sources
Baltsavias
2000 4 0 2 6
↑ Poor grade SAH in early treatment group, uncertain age distribution; outcome assessment non-blinded/self-
report (mailed questionnaire or telephone)
Byrne 2001 2 0 2 4 Pre-1994, only non-operable patients included; ↑ poor grade SAH in early treatment group; distribution of age
not assessed; outcome assessment non-blinded
Consoli 2013 4 0 2 6 ↑Poor grade SAH in early treatment group; age distribution not assessed; outcome assessment non-
blinded/self-report (telephone)
Dorhout Mees
2012 2 0 2 4
ISAT trial cohort (not generalizable); may be underlying reasons for treatment delay; unknown distribution of
baseline variables in coiling group; outcome assessment by self-reported questionnaire
Gu 2012 4 2 1 7 Outcome assessment non-blinded, loss to follow-up
Johansson
2004 3 0 2 5 Elderly patients only; unknown distribution of baseline clinical variables; outcome assessment not blinded
Lawson 2010 4 2 1 7 Assessed outcome at discharge (ie: inadequate follow-up), not blinded
Luo 2015 3 2 1 6
Restricted to poor grade patients; clearly documented that delayed treatment was not due to clinical decision
but other factors; no statistical difference in age and WFNS bw groups; some patients interviewed over
telephone for outcomes; no mention of loss to follow up (patients without routine follow up were excluded )
Norback 2005 4 0 2 6 Unknown distribution of baseline clinical variables; outcome assessment not blinded
Oudshoorn
2014 (UMC) 3 2 2 7 No information on why treatment delayed; short follow-up
Oudshoorn
2014 (ISAT) 2 1 1 4 ISAT cohort; WFNS not equally distributed; outcome by self reported questionnaires, short follow-up
Phillips 2011 3 0 1 4 Coiling not primary treatment modality, unknown distribution of baseline clinical variables; outcome
assessment non-blinded, loss to follow-up
Qian 2014 2 2 1 5 Excluded cases with diagnostic CT performed >6-hours post SAH; uncertain whether coiling primary modality
and reasons for treatment delay, outcome assessment not blinded, loss to follow-up
Sandstrom
2013 3 1 2 6 Restricted to poor grade patients; age distribution uncertain; loss to follow-up
Sluzewski
2003 2 0 1 3
In early part of study, only high surgical risk aneurysms treated with coiling; unknown distribution of baseline
clinical variables; outcome assessment not blinded; only mean follow-up time provided
Wikholm
2000 3 1 1 5
Rejected clipping as first choice, age distribution unknown, no mention of blinding, outcomes assessed at
discharge
Table III: Timing categorization of included studies
Abbreviations: NS – not specified
STUDY
Number of timing
categories
Upper limit of earliest timing
category (days)
Upper limit of next timing
category (days)
Upper limit of next timing
category (days)
Upper limit of next timing
category (days)
ApSimon 1998 4 4 14 28 NS
Baltsavias 2000 3 2 10 30 .
Byrne 2001 2 6 30 . .
Consoli 2013 3 0.5 2 NS .
Dorhout Mees 2012 4 2 4 10 NS
Gu 2012 2 1 NS . .
Johansson 2004 3 3 10 21 .
Lawson 2010 2 3 10 . .
Luo 2015 2 1 NS . .
Norback 2005 3 3 10 21 .
Oudshoorn 2014 (UMC) 2 1 3 . .
Oudshoorn 2014 (ISAT) 2 1 3 . .
Phillips 2011 4 1 3 10 NS
Qian 2014 4 1 3 10 NS
Sandstrom 2013 2 1 NS . .
Sluzewski 2003 2 3 60 . .
Wikholm 2000 2 2 15 . .
Table IV: Poor outcome – distribution of confounders (poor grade SAH and age) in early versus late treatment groups
Definition of "early"
(days) STUDY
Definition of “late"
(h/d)
Poor grade SAH early
group (%)
Poor grade SAH late
group (%)
P-value (Chi-
Square)
Mean age early
group (SD)
Mean age late
group (SD)
P-value (t-
test)
1
Oudshoorn 2014
(UMC) 24-72h 32.8 23.9 0.27 55.1 (12.2) 56.6 (14.3) 0.49
Oudshoorn 2014
(ISAT) 24-72h 16.7 4.9 0.005* 49.4 (10.9) 50.8 (10.7) 0.82
Phillips 2011 24-72h N/A N/A 0.81 N/A N/A 0.50
Qian 2014 24-72h 4.1 6.4 0.49 56.2 56.3 NS
Gu 2012 >24h 28.6 22.5 0.50 74.5 75.7 0.20
Luo 2015 >24h 100 100 - 62.6 55.6 0.11
Phillips 2011 >24h N/A N/A N/A* N/A N/A N/A*
Qian 2014 >24h 4.1 5.6 0.47 56.2 55.5 NS
Sandstrom 2013 >24h 100 100 - N/A N/A N/A*
2
Baltsavias 2000 3-30d 29.9 19.5 0.005* 48.9 51.4 N/A*
Consoli 2013 >48h 33.0 13.4 0.0001* N/A N/A N/A*
Dorhout Mees 2012 >2d N/A N/A N/A* N/A N/A N/A*
3
Johansson 2004 4-21d N/A N/A N/A* N/A N/A N/A*
Lawson 2010 4-10d 29.4 35.7 0.32 58 53 0.26
Norback 2005 4-21d N/A N/A N/A* N/A N/A N/A*
Phillips 2011 >72h N/A N/A N/A* N/A N/A N/A*
Qian 2014 >72h 4.5 5.4 0.72 56.2 55.4 NS
Sluzewski 2003 4-60d N/A N/A N/A* N/A N/A N/A*
4 ApSimon 1998 >4d 15.0 3.2 0.29 N/A N/A N/A*
6 Byrne 2001 6-30d 29.2 19.4 0.048* N/A N/A N/A*
Abbreviations: h – hours; d – days; NS – not statistically significant (p-value not provided); N/A – not available, cannot be calculated
from provided data
Annotations:
* Comparability of groups not demonstrated (statistically significant difference between groups, or data not available)
Table V: Case fatality – distribution of confounders (poor grade SAH and age) in early versus late treatment groups
Definition of "early"
(days) STUDY
Definition of “late"
(h/d)
Poor grade SAH early
group (%)
Poor grade SAH late
group (%)
P-value (Chi-
Square)
Mean age early
group (SD)
Mean age late
group (SD)
P-value (t-
test)
1
Oudshoorn 2014
(UMC) 24-72h 32.8 23.9 0.27 55.1 (12.2) 56.6 (14.3) 0.49
Oudshoorn 2014
(ISAT) 24-72h 16.7 4.9 0.005* 49.4 (10.9) 50.8 (10.7) 0.82
Qian 2014 24-72h 4.1 6.4 0.49 56.2 56.3 NS
Qian 2014 >24h 4.1 5.6 0.47 56.2 55.5 NS
2 Baltsavias 2000 3-30d 29.9 19.5 0.005* 48.9 51.4 N/A*
Consoli 2013 >48h 33.0 13.4 0.0001* N/A N/A N/A*
Wikholm 2000 3-15d N/A N/A NS N/A N/A N/A*
3 Lawson 2010 4-10d 29.4 35.7 0.32 58 53 0.26
Qian 2014 >72h 4.5 5.4 0.72 56.2 55.4 NS
Abbreviations: h – hours; d – days; NS – not statistically significant (p-value not provided); N/A – not available, cannot be calculated
from provided data
Annotations:
* Comparability of groups not demonstrated (statistically significant difference between groups, or data not available)
Appendix: Search Strategy (up to date as of August 12, 2015)
Database: Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) <1946 to Present>
Search Strategy:
--------------------------------------------------------------------------------
1 exp Subarachnoid Hemorrhage/ (15993)
2 intracranial hemorrhages/ or cerebral hemorrhage/ (29936)
3 intracranial aneurysm/ (20870)
4 rupture, spontaneous/ (17187)
5 3 and 4 (1846)
6 aneurysm, ruptured/ (5401)
7 exp brain/ or exp meninges/ (965694)
8 6 and 7 (465)
9 ((subarachnoid or arachnoid) adj6 (haemorrhage$ or hemorrhage$ or bleed$ or blood$)).tw. (17720)
10 vasospasm, intracranial/ (2192)
11 ((cerebral or intracranial or cerebrovascular) adj6 (vasospasm or spasm)).tw. (3806)
12 sah.tw. (6744)
13 1 or 2 or 5 or 8 or 9 or 10 or 11 or 12 (53224)
14 exp Endovascular Procedures/ (78724)
15 exp Embolization, Therapeutic/ (28470)
16 coil$.ti,ab. (40619)
17 14 or 15 or 16 (140601)
18 13 and 17 (2727)
19 exp Time Factors/ (977585)
20 Early.ti. (203591)
21 (same adj2 day).ti,ab. (9082)
22 24 hour$.ti,ab. (106482)
23 48 hours.ti,ab. (33847)
24 delay$.ti. (50671)
25 timing.ti,ab. (79625)
26 Late.ti. (58017)
27 or/19-26 (1402951)
28 18 and 27 (320)
29 remove duplicates from 28 (319)
30 limit 29 to case reports (70)
31 29 and case report.ti. (23)
32 30 or 31 (74)
33 29 not 32 (245)
***************************
Database: EBM Reviews - Cochrane Database of Systematic Reviews <2005 to December 2013>, EBM Reviews - ACP Journal
Club <1991 to January 2014>, EBM Reviews - Database of Abstracts of Reviews of Effects <1st Quarter 2014>, EBM Reviews
- Cochrane Central Register of Controlled Trials <January 2014>, EBM Reviews - Cochrane Methodology Register <3rd
Quarter 2012>, EBM Reviews - Health Technology Assessment <1st Quarter 2014>, EBM Reviews - NHS Economic
Evaluation Database <1st Quarter 2014>
Search Strategy:
--------------------------------------------------------------------------------
1 exp Subarachnoid Hemorrhage/ (361)
2 intracranial hemorrhages/ or cerebral hemorrhage/ (658)
3 intracranial aneurysm/ (317)
4 rupture, spontaneous/ (100)
5 3 and 4 (28)
6 aneurysm, ruptured/ (87)
7 exp brain/ or exp meninges/ (7910)
8 6 and 7 (10)
9 ((subarachnoid or arachnoid) adj6 (haemorrhage$ or hemorrhage$ or bleed$ or blood$)).tw. (1188)
10 vasospasm, intracranial/ (88)
11 ((cerebral or intracranial or cerebrovascular) adj6 (vasospasm or spasm)).tw. (363)
12 sah.tw. (383)
13 1 or 2 or 5 or 8 or 9 or 10 or 11 or 12 (2016)
14 exp Endovascular Procedures/ (5050)
15 exp Embolization, Therapeutic/ (559)
16 coil$.ti,ab. (611)
17 14 or 15 or 16 (6112)
18 13 and 17 (94)
19 exp Time Factors/ (46862)
20 Early.ti. (15763)
21 (same adj2 day).ti,ab. (92069)
22 24 hour$.ti,ab. (15607)
23 48 hours.ti,ab. (4502)
24 delay$.ti. (2841)
25 timing.ti,ab. (3709)
26 Late.ti. (2470)
27 or/19-26 (160154)
28 18 and 27 (20)
***************************
Database: Embase Classic+Embase <1947 to 2014 Week 06>
Search Strategy:
--------------------------------------------------------------------------------
1 exp subarachnoid hemorrhage/ (30989)
2 brain artery aneurysm rupture/ or brain hemorrhage/ or brain vasospasm/ (70157)
3 (intracranial aneurysm/ or brain artery aneurysm/) and (rupture/ or artery rupture/ or rupture$.tw.) (6599)
4 aneurysm rupture/ and (exp brain/ or exp meninx/) (1572)
5 ((subarachnoid or arachnoid$) adj6 (haemorrhage$ or hemorrhage$ or haematoma$ or hematoma$ or bleed$ or blood$)).tw.
(25456)
6 ((brain or cereb$ or intracranial) adj3 aneurysm$ adj3 ruptur$).tw. (3768)
7 ((cerebral or intracranial or cerebrovascular) adj6 (vasospasm or spasm)).tw. (5321)
8 sah.ti,ab. (9613)
9 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 (101458)
10 exp coil embolization/ (6288)
11 coil$.ti,ab. (52481)
12 exp endovascular surgery/ (17896)
13 10 or 11 or 12 (70230)
14 9 and 13 (4957)
15 time/ (437888)
16 timing.ti,ab. (102325)
17 Time Factor$.ti,ab. (2428)
18 Early.ti. (272672)
19 (same adj2 day).ti,ab. (13958)
20 24 hour$.ti,ab. (162815)
21 48 hour$.ti,ab. (57250)
22 delay$.ti. (64268)
23 Late.ti. (76303)
24 or/15-23 (1111704)
25 14 and 24 (380)
26 limit 25 to (letter or note or report) (11)
27 case report.ti. (213881)
28 26 or 27 (213892)
29 25 not 28 (349)
30 remove duplicates from 29 (334)
***************************
Web of Science 301
TOPIC: (subarachnoid hemorrhage) AND TOPIC: (coil*) AND TOPIC: (time or timing)
Refined by: DOCUMENT TYPES=( ARTICLE OR PROCEEDINGS PAPER OR REVIEW )
Indexes=SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH Timespan=All years