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Intravenous immunoglobulin for the treatment of childhood encephalitis

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Appendices

Appendix 1. Search strategies

Source

Search strategy

CENTRAL (The Cochrane Library) (latest issue)

#1 encephalitis:ti,ab,kw (Word variations have been searched)
#2 meningoencephalitis:ti,ab,kw (Word variations have been searched)
#3 ((brain or cerebral) near/2 (infection* or infectious or inflamm* or swell*)):ti,ab,kw (Word variations have been searched)
#4 #1 or #2 or #3
#5 MeSH descriptor: [Immunoglobulins, Intravenous] explode all trees
#6 ((intravenous or intra‐venous) near/3 immunoglobulin*):ti,ab,kw (Word variations have been searched)
#7 ivig or igiv:ti,ab,kw (Word variations have been searched)
#8 immunoglobulin* or immunotherap*:ti (Word variations have been searched)
#9 #5 or #6 or #7 or #8
#10 #4 and #9

MEDLINE (PubMed) (1966 to date)

1 exp Encephalitis/

2 encephalitis.ti,ab.

3 meningoencephalitis.ti,ab.

4 ((brain or cerebral) adj2 (infection* or infectious or

inflamm* or swell*)).ti,ab.

5 1 or 2 or 3 or 4

6 adolescent/ or exp child/ or infant/ or infant, newborn/

7 (child* or preschool* or pre‐school* or schoolchild* or

infant* or infancy or baby or babies or toddler* or teen*

or adolescen* or youth*).ti,ab.

8 6 or 7

9 Immunoglobulins, Intravenous/

10 ((intravenous or intra‐venous) adj3

immunoglobulin*).ti,ab.

11 (ivig or igiv).ti,ab.

12 (immunoglobulin* or immunotherap*).ti.

13 9 or 10 or 11 or 12

14 5 and 8 and 13

15 limit 14 to "reviews (maximizes specificity)"

16 randomised controlled trial.pt.

17 controlled clinical trial.pt.

18 randomized.ab.

19 placebo.ab.

20 drug therapy.fs.

21 randomly.ab.

22 trial.ab.

23 groups.ab.

24 16 or 17 or 18 or 19 or 20 or 21 or 22

or 23

25 exp animals/ not humans.sh.

26 24 not 25

27 14 and 26

EMBASE (embase.com) (1974 to date)

1 exp *Encephalitis/

2 encephalitis.ti,ab.

3 meningoencephalitis.ti,ab.

4 ((brain or cerebral) adj2 (infection* or infectious or

inflamm* or swell*)).ti,ab.

5 1 or 2 or 3 or 4

6 adolescent/ or child/ or boy/ or girl/ or infant/ or preschool

child/ or school child/ or toddler/

7 (child* or preschool* or pre‐school* or schoolchild* or

infant* or infancy or baby or babies or toddler* or teen* or

adolescen* or youth*).ti,ab.

8 6 or 7

9 exp *immunoglobulin/ and intravenous drug administration/

10 exp *immunoglobulin/iv [Intravenous Drug Administration]

11 ((intravenous or intra‐venous) adj3 immunoglobulin*).ti,ab.

12 (ivig or igiv).ti,ab.

13 (immunoglobulin* or immunotherap*).ti.

14 9 or 10 or 11 or 12 or 13

15 5 and 8 and 14

16 limit 15 to "reviews (maximizes specificity)"

17 randomised controlled trial/

18 controlled clinical trial/

19 single blind procedure/ or double blind procedure/

20 crossover procedure/

21 random*.tw.

22 placebo*.tw.

23 ((singl* or doubl*) adj (blind* or mask*)).tw.

24 (crossover or cross over or factorial* or latin square).tw.

25 (assign* or allocat* or volunteer*).tw.

26 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25

Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO host) (1981 to date)

Latin American and Caribbean Health Science Information Database (LILACS) (Bireme) (1982 to date)

ClinicalTrials.gov

(www.clinicaltrials.gov)

(encephalitis OR meningoencephalitis) AND (immunoglobulin OR immunoglobulins OR ivig OR igiv OR immunotherapy)

ICTRP Search Portal

(http://apps.who.int/trialsearch)

(encephalitis OR meningoencephalitis) AND (immunoglobulin OR immunoglobulins OR ivig OR igiv OR immunotherapy)

Science Citation Index Expanded (SCI‐EXPANDED) & Conference Proceedings Citation Index‐ Science (CPCI‐S)(Web of Science Core Collection, Thomson Reuters) (1945 to date)

# 1 TOPIC: (encephalitis OR meningoencephalitis) OR TOPIC: (((brain or cerebral) NEAR/2 (infection* or infectious or inflamm* or swell*)))

# 2 TOPIC: (child* or preschool* or pre‐school* or schoolchild* or infant* or infancy or baby or babies or toddler* or teen* or adolescen* or youth*)

# 3 TOPIC: (((intravenous or intra‐venous) NEAR/3 immunoglobulin*)) OR TOPIC: (ivig or igiv) OR TITLE: (immunoglobulin* or immunotherap*)

# 4 #3 AND #2 AND #1

# 5 TOPIC: (random* or blind* or allocat* or assign* or trial* or placebo* or crossover* or cross‐over*)

# 6 #5 AND #4

Global Health Library (Virtual Health Library) (http://www.globalhealthlibrary.net/php/index.php)

(encephalitis OR meningoencephalitis) AND (immunoglobulin OR immunoglobulins OR ivig OR igiv OR immunotherapy)

Database of Abstracts of Reviews of Effects (DARE)

(encephalitis OR meningoencephalitis) AND (immunoglobulin OR immunoglobulins OR ivig OR igiv OR immunotherapy)

Appendix 2. Newcastle Ottawa Scale (Cohort studies)

Note: a study can be awarded a maximum of one star for each numbered item within the 'Selection' and 'Outcome'
categories. A maximum of two stars can be given for 'Comparability'.

Selection

1) Representativeness of the exposed cohort
a) truly representative of the average _______________ (describe) in the community *
b) somewhat representative of the average ______________ in the community *
c) selected group of users e.g. nurses, volunteers
d) no description of the derivation of the cohort

2) Selection of the non‐exposed cohort
a) drawn from the same community as the exposed cohort *
b) drawn from a different source

c) no description of the derivation of the non‐exposed cohort

3) Ascertainment of exposure
a) secure record (e.g. surgical records) *
b) structured interview *
c) written self‐report
d) no description
4) Demonstration that outcome of interest was not present at start of study
a) yes *
b) no

Comparability

1) Comparability of cohorts on the basis of the design or analysis
a) study controls for _____________ (select the most important factor) *
b) study controls for any additional factor * (This criteria could be modified to indicate specific control for a second important
factor)

Outcome

1) Assessment of outcome
a) independent blind assessment *
b) record linkage *
c) self‐report
d) no description

2) Was follow‐up long enough for outcomes to occur
a) yes (select an adequate follow‐up period for outcome of interest) *
b) no

3) Adequacy of follow‐up of cohorts
a) complete follow‐up ‐ all subjects accounted for *
b) subjects lost to follow‐up unlikely to introduce bias ‐ small number lost ‐ > ____ % (select an adequate %) follow‐up, or
description provided of those lost) *
c) follow‐up rate < ____% (select an adequate %) and no description of those lost

Appendix 3. Newcastle Ottawa Scale (Case‐control studies)

Selection

1) Is the case definition adequate?
a) yes, with independent validation *
b) yes, e.g. record linkage or based on self‐reports
c) no description

2) Representativeness of the cases
a) consecutive or obviously representative series of cases *
b) potential for selection biases or not stated

3) Selection of controls
a) community controls *
b) hospital controls
c) no description

4) Definition of controls
a) no history of disease (endpoint) *
b) no description of source

Comparability

1) Comparability of cases and controls on the basis of the design or analysis
a) study controls for _______________ (Select the most important factor) *
b) study controls for any additional factor * (This criteria could be modified to indicate specific control for a second important
factor)

Exposure

1) Ascertainment of exposure
a) secure record (e.g. surgical records) *
b) structured interview where blind to case/control status *
c) interview not blinded to case/control status
d) written self‐report or medical record only
e) no description

2) Same method of ascertainment for cases and controls
a) yes *
b) no

3) Non‐response rate
a) same rate for both groups *
b) non‐respondents described
c) rate different and no designation