Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Cachat, 2012

individual study characteristics deduced from Cachat, 2012 and individual studies.

SR and meta-analysis of RCTs / quasi randomized trials

Literature search from 1966 to September 2011

A: Mortensson, 1984

B: Hsiao, 1988

C: Franken, 1983

D: Haase, 1979

Study design:

A: RCT

B: RCT

C: RCT (double blind)

D: RCT (double blind)

Setting and Country:

Hospital, countries not stated

Source of funding:

none

Inclusion criteria SR: RCT or quasi RCT, reporting effectiveness of glucagon in children with intussusception.

Exclusion criteria SR: not described

4 studies included

Important patient characteristics at baseline:

Number of patients:

A: 176

B: 63

C: 30

D: 69 healthy mongrel puppies

Age (months):

A: median 9 (range: 1-5.5)

B: mean 12.6±10

C: <3years

D: -

Groups comparable at baseline? Yes

Glucagon

A: 0.05 mg glucagon/kg body weight intramuscularly before attempts at reduction were started (n=69)

B: Glucagon (IV) (n=38)

C: intravenous administration of glucagon or placebo (0.05 mg/kg (n=15)

D: Glucagon (n=35 animals)

Reference

A: reference (n=119)

B: Reference (n=25)

C: IV administration of placebo (n=15)

D: Reference (n=35 animals)

End-point of follow-up:

Not stated

For how many participants were no complete outcome data available?

Not stated

Percentage of successful radiological reductions

Effect measure: % succes

A: 84% versus 76%, NS

B: 42% vs, 56%, p>0.05

C: 53% versus 53%, NS

D: 65% versus 74%, p=0.5

Pooled effect: not calculated

Facultative:

Comments of authors on study quality:

A: Poor allocation method, no

blinding. No difference between groups. Maximum of three attempts.

B: Unclear allocation method. No difference between groups. No difference between groups according to the type of intussusception (ileo-colic versus ileo-ileo versus ileo-ileo-colic). No difference with duration of symptoms. Maximum of two attempts.

C: Unclear allocation method. No difference between groups. No difference when taking into account successful reductions observed after time limit or found reduced at the time of laparotomy. Maximum of three attempts.

D: Experimental animal study. Unclear allocation method. No difference between groups, although glucagon significantly increased

the likelihood of complete

eduction on the first attempt.

Maximum of three attempts.

Study

First author, year

Appropriate and clearly focused question?¹

Yes/no/unclear

Comprehensive and systematic literature search?²

Yes/no/unclear

Description of included and excluded studies?³

Yes/no/unclear

Description of relevant characteristics of included studies?⁴

Yes/no/unclear

Appropriate adjustment for potential confounders in observational studies?⁵

Yes/no/unclear/notapplicable

Assessment of scientific quality of included studies?⁶

Yes/no/unclear

Enough similarities between studies to make combining them reasonable?⁷

Yes/no/unclear

Potential risk of publication bias taken into account?⁸

Yes/no/unclear

Potential conflicts of interest reported?⁹

Yes/no/unclear

Cachet, 2012

yes

Yes

No: no description of excluded studies

Yes

Not applicable

No

Yes

No

Yes

1. Research question (PICO) and inclusion criteria should be appropriate and predefined
2. Search period and strategy should be described; at least Medline searched; for pharmacological questions at least Medline + EMBASE searched
3. Potentially relevant studies that are excluded at final selection (after reading the full text) should be referenced with reasons
4. Characteristics of individual studies relevant to research question (PICO), including potential confounders, should be reported
5. Results should be adequately controlled for potential confounders by multivariate analysis (not applicable for RCTs)
6. Quality of individual studies should be assessed using a quality scoring tool or checklist (Jadad score, Newcastle-Ottawa scale, risk of bias table etc.)
7. Clinical and statistical heterogeneity should be assessed; clinical: enough similarities in patient characteristics, intervention and definition of outcome measure to allow pooling? For pooled data: assessment of statistical heterogeneity using appropriate statistical tests (e.g. Chi-square, I2)?
8. An assessment of publication bias should include a combination of graphical aids (e.g., funnel plot, other available tests) and/or statistical tests (e.g., Egger regression test, Hedges-Olken). Note: If no test values or funnel plot included, score “no”. Score “yes” if mentions that publication bias could not be assessed because there were fewer than 10 included studies.
9. Sources of support (including commercial co-authorship) should be reported in both the systematic review and the included studies. Note: To get a “yes,” source of funding or support must be indicated for the systematic review AND for each of the included studies

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Lin, 2000

Type of study:

RCT

Setting:

Hospital

Country: Taiwan

Source of funding: not stated

Inclusion criteria:

Children between first week of life and 6 months with intussusception

Exclusion criteria: not stated

N total at baseline: 281

Intervention: 144

Control:137

Important prognostic factors²:

For example

age ± SD:

I: 18.2±5.1

C: 20.3±4.7

Sex:

I: 97 (67%) M

C: 99 (72%) M

Mean duration of symptoms (days)

I: 1.7±0.9

C: 2.1±1.3

Groups comparable at baseline? yes

Intramuscular dexamethasone sodium phosphate (0.5mg/kg)

Saline pre-treatment

Length of follow-up:

6 months

Loss-to-follow-up:

Not stated

Incomplete outcome data:

Not stated

I versus C

Successful reduction

122/144 (84.7%) versus 117/137 (85.4%)

NS

Recurrence within 72h:

0/144 versus 3/137

NS

Early recurrence (ERI)

Defined as recurrence within 1 week:

0/144 versus 6/137 (5.1%)

P<0.05

Recurrence at 6 monts:

1/144 (0.8%) versus 8/137 (6.8%)

P<0.05

Complications:

Bowel perforation: 0 versus 0

Mortality: 0 versus 0

Study description is only 1 page, information on methods are missing, as well as some information on loss of follow up, etc.

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Lin, 2000

Not described

Unclear (no description)

Unclear (no information)

Unclear (no information)

Unclear (no information)

Unlikely

Unclear (no information)

Unlikely (no switches).

1. Randomisation: generation of allocation sequences have to be unpredictable, for example computer generated random-numbers or drawing lots or envelopes. Examples of inadequate procedures are generation of allocation sequences by alternation, according to case record number, date of birth or date of admission.
2. Allocation concealment: refers to the protection (blinding) of the randomisation process. Concealment of allocation sequences is adequate if patients and enrolling investigators cannot foresee assignment, for example central randomisation (performed at a site remote from trial location) or sequentially numbered, sealed, opaque envelopes. Inadequate procedures are all procedures based on inadequate randomisation procedures or open allocation schedules..
3. Blinding: neither the patient nor the care provider (attending physician) knows which patient is getting the special treatment. Blinding is sometimes impossible, for example when comparing surgical with non-surgical treatments. The outcome assessor records the study results. Blinding of those assessing outcomes prevents that the knowledge of patient assignement influences the proces of outcome assessment (detection or information bias). If a study has hard (objective) outcome measures, like death, blinding of outcome assessment is not necessary. If a study has “soft” (subjective) outcome measures, like the assessment of an X-ray, blinding of outcome assessment is necessary.
4. Results of all predefined outcome measures should be reported; if the protocol is available, then outcomes in the protocol and published report can be compared; if not, then outcomes listed in the methods section of an article can be compared with those whose results are reported.
5. If the percentage of patients lost to follow-up is large, or differs between treatment groups, or the reasons for loss to follow-up differ between treatment groups, bias is likely. If the number of patients lost to follow-up, or the reasons why, are not reported, the risk of bias is unclear
6. Participants included in the analysis are exactly those who were randomized into the trial. If the numbers randomized into each intervention group are not clearly reported, the risk of bias is unclear; an ITT analysis implies that (a) participants are kept in the intervention groups to which they were randomized, regardless of the intervention they actually received, (b) outcome data are measured on all participants, and (c) all randomized participants are included in the analysis.

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Esposito, 2015

Type of study:

Observational

Setting:

Hospital

Country:

Italy

Source of funding: none.

Inclusion criteria:

Clinical suspicion and imaging conformation of ileo-colic, ileo-ileo-colic or colo-colic intussusception

Exclusion criteria: signs of shock, peritonitis, perforation, surgical demonstration of intussucueption secondary to the presence of pathological lead points

N total at baseline: 411

Intervention: 254

Control: 144

Important prognostic factors²:

Mean age:

14 months

Sex:

240 M, 171 F

Groups comparable at baseline? Not stated

Barium enema with premedication:

-          Anti-oedematous agent: betamethasone 0.1-0.2mg/kg i.v. administered 1-1.5h before barium enema

-          Mild sedative: midazolam 0.5mg/kg (max 15mg) oral or intra-nasal, administered 30min before barium enema

-          Gastroprotective agent: ranitidine 2-4 mg/kg

Barium enema without premedication.

Length of follow-up:

72h postoperatively

Loss-to-follow-up:

none

Incomplete outcome data:

N=11: contraindication for barium enema. N=2: received pharmacological premedication and no longer exhibited intussusception before the barium enema.

Reduction of intussusception (contrast agent could be seen to pass over to the ileocecal valve):

I: 122 (85%)

C: 165 (65%)

Perforation:

0 versus 0

Relapse (within 72h):

0 versus 0

Not randomised!

patients 2007 – 2010: control group

2011-2013: intervention group

In control group fluoroscopy was not available (acquisition of the radiographs was performed if necessary).

Purenne, 2012

Type of study:

Retrospective cohort

Setting:

Hospital

Country: Israel

Source of funding: departmental funds (none).

Inclusion criteria:

Patients hospitalized between 1989 and 2008 with diagnosis of intussusception and receiving air edema.

Exclusion criteria: -

N total at baseline: 509 episodes (433 patients)

Intervention: 172

Control:337

Important prognostic factors²:

Median age: 16 months (range: 2 months – 12 years)

I: 17 [22]

C: 15 [18]

Sex (M/F):

I: 120/52

C: 223/114

Type:

Ileocolic: 444

Ileoileal: 24

Not specified: 29

Lead point:

Merckel’s diverticulitum: 9

Appendicitis: 5

Other: 5

Groups comparable at baseline? Yes

General Anaesthesia (GA), n=172

>2000

Propofol (4-6mg /kg) and succinylcholine (1.5-2.0mg/kg) for tracheal intubation and maintained either with small bolusus of propofol or with sevoflurane (0.5-1 Mac)

Sedation n=337

1989-2000: i.v. flunitrazepam (0.05±0,02 mg-kg, mean±sd) and then midazolam (0.33±0.18 mg-kg, mean±sd)

>2000: deeper sedation with propofol or low concentration of halothane (n=30)

Length of follow-up:

Loss-to-follow-up:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Bowel perforation:

0 versus 0

Success rate, univariable analysis:

155 (90%) versus 285 (85%), OR 1.07, p=0.100

Success rate, multivariable analysis, matching using propensity score (GA versus sedation, sex, age, year, time interval between first symptoms and enema):

OR (95%-CI):

GA/SED: 5.64 (2.81-12.65), p=0.013

Sex (M/F): 2.09 (0.89-4.82)

P=0.153

Age: 0.89 (0.96-1.02)

P=0.055

Year: 0.90 (0.81-1.08)

P=0.185

Time to enema (<6, 6-12, 12-24, 24-48, >48h): 0.87 (0.70-0.95)

P=0.014

The success rate increased over the years.

Spontanously resolved at time of edema: n=39 (of 509 episodes)

Main predictors of success were: short time interval (<12h) and use of GA

Note: complications not clearly reported. Recurrence is stated, but not compared for groups. (high recurrence as far as estimable)

Suzuki, 1999

Type of study:

Non-randomized clinical trial

Setting:

Hospital

Country: Japan

Source of funding: not stated

Inclusion criteria: patients with clinically suspected, and confirmed (by barium enema) intussusception

Exclusion criteria:

-

N total at baseline: 74

Intervention: 39 patients (43 cases)

Control: 35 (39 cases)

Important prognostic factors²:

Age in months median (range):

I: 9 (2 months – 5 years)

C: 12 (2 months – 5 years)

Sex (F/M):

I: 12 / 27

C: 13 / 22

Groups comparable at baseline? yes

General anaesthesia (April 1974-june 1988)

Induced with thiopental and followed by nitrous oxide, oxygen and halothane with endotracheal tube placed.

No premedication for sedation (July 1988-January 1994)

Length of follow-up:

Not stated (while in hospital)

Loss-to-follow-up:

None

Incomplete outcome data:

None

Successful reduction

considered successful if the ileum filled freely with refluxing barium:

I: 39 (91%)

C: 37 (95%)

P=0.3

Perforation

1 (fatal) versus 1

Not randomized!

2 perforations, of which 1 was fatal (both children <6months). Barium enema technique was changed after fatality.

Other factors were studied:

Group with successful reduction (n=76) versus unsuccessful reduction (n=6)

Age <12 months:

40 (52%) versus 4 (50%), P=0.6

Illness >24h:

9 (12%) versus 1 (17%), P=0.5

Ilio-iliocolic type:

14 (19%) versus 3 (50%), p=0.5

Eisapour, 2015

Type of study:

Quasi-randomized controlled trial

Setting:

Hospital

Country: Iran

Source of funding: not stated

Inclusion criteria:

6 months – 4 years, definite diagnosis of ileocolic intussusception based on sonographic findings.

Exclusion criteria: pathologic lead point, passage of more than 48 hours since onset of symptoms, presence of signs of peritonitis or bowel perforation, dehydration, lethargy, history of a known gastro-intestinal disease such as celiac disease, cystic fibrosis, history of a chronic hypoxic pulmonary disease, cyanotic heart disease, history of previous intussusception and history of allergy to benzodiazepine.

N total at baseline: 32

Intervention: 16

Control: 16

Important prognostic factors:

Age (months) ± SD:

I: 19±9

C: 23.3±14.9

P=0.449

Sex:

I: 62.5% M

C: 43.8% M

P=0.288

Onset of symptoms

<10 hours

I: 2 (12.5%)

C: 7 (43.8%)

10-20 hours

I: 14 (87.5%)

C: 2 (12.5%)

>21 hours

I: -

C: 7 (43.8%)

P<0.005

Groups comparable at baseline? No, onset of symptom time differs between groups.

Midazolam

5 mg per mil of i.v. midazolam 5 minutes before reduction (determined based on body weight)

Barium reduction

Placebo (i.v. sterile water)

Length of follow-up:

In hospital stay

Loss-to-follow-up:

-

Incomplete outcome data:

-

Successful reduction

Entry of barium into ileal loops is viewed in the graph

I: 15 (93.8%)

C: 11 (86.8%)

Mean duration of procedure

I: 11.35±34.8 minutes

C: 19.2±32.73 minutes

P=0.733

Randomization method: every other one

No side effects/complications are mentioned.

Touloukian, 1987

Type of study:

Retrospective observational

Setting:

Hospital

Country: USA

Source of funding: not stated

Inclusion criteria:

ileocolic intussusception treated at the Yale-

New Haven Hospital between Jan 1, 1974, and Dec

31, 1984

Exclusion criteria:

N total at baseline: 69

Intervention: 47

Control: 22

Important prognostic factors²:

Median age

I: 9 months

C: 42.2 months

Groups comparable at baseline? No

premedication with meperidine (Demerol; 1.0 mg/

kg) combined with promethazine (Phenergan; 1.0

mg/kg) and chlorpromazine (Thorazine, 0.5 mg/kg)

or secobarbital (Seconal) in three early cases. These patients were selected in a nonrandomized fashion,

with increasing frequency through the study period,

No premedication

Length of follow-up:

Not stated

Loss-to-follow-up:

No information

Incomplete outcome data:

No information

I versus C

Successful reduction

Reduction was considered complete only if the

colon was fully visualized and the terminal ileum

filled freely with refluxing barium.

32/47 (68%) versus 8/22 (36%), p<0.05

Pain was the most frequent complaint, occurring

in 96% of cases, and was followed by vomiting in

84%. Either gross or occult rectal bleeding was

reported by history or found during physical examination

in 81% of the cases. Excluding those

with only Hemoccult-positive stool, the incidence

was 54%. The classic triad of abdominal pain, vomiting,

and grossly bloody stool was present in only

43% of the cases.

Pre-intervention

At intervention

Post-intervention

Study reference

Risk of Bias due to confounding¹

Risk of Bias in selection of participants into the study²

Risk of Bias in measurement of exposure³

Risk of Bias due to departures from intended exposure(s)⁴

Risk of Bias due to missing data⁵

Risk of Bias in measurement of outcomes⁶

Risk of Bias in selection of the reported result⁷

Purenne, 2012

Critical

Intervention and control were used over different years, likely that factors other than studied intervention influence the outcomes. Adjustment using propensity score, however unclear if all relevant variable are adjusted for.

Low

All patients were include.

Low

Exposure was medication i.v. exposure status well defined.

Serious

Co-exposure likely, due to different years of treatment.

Low

No incomplete data

Low

Objective outcome measure

Moderate

Not all relevant outcomes reported on, different types of multivariate analysis performed.

Susuki, 1999

Critical

Intervention and control were used over different years, likely that factors other than studied intervention influence the outcomes. Not adjusted for.

Low

All patients were included.

Low

Exposure was medication i.v. exposure status well defined.

Serious

Co-exposure likely, due to different years of treatment.

Low

No incomplete data

Low

Objective outcome measure

Moderate

Complications/side effects not clearly reported on.

Espisito

Critical

Intervention and control were used over different years, likely that factors other than studied intervention influence the outcomes. Not adjusted for.

Low

All patients were included.

Low

Exposure was medication i.v. exposure status well defined.

Serious

Co-exposure likely, due to different years of treatment.

Low

No incomplete data.

Low

Objective outcome measure.

Moderate

Complications/side effects not clearly reported on.

Eisapour, 2015

Critical

Baseline characteristics in intervention and control group differed, and no adjustment in the analysis.

Low

Clear in- and exclusion criteria.

Low

Exposure status well defined.

Low

Groups were treated during same time, unlikely co-exposures cause risk of bias.

Low

No incomplete data

Low

Objective outcome measure

Critical

Authors were e-mailed to ask for explanation, however no reaction was received.

Touloukian, 1987

Critical

Baseline characteristics in intervention and control group differed, and no adjustment in the analysis.

Low

All patients were included.

Low

Exposure was medication i.v. exposure status well defined.

Low

Groups were treated during same time, unlikely co-exposures cause risk of bias.

Low

No incomplete data

Low

Objective outcome measure

Moderate

Complications/side effects not clearly reported on.

1. Is confounding of the effect of the exposure of interest (in other words, intervention or risk factor) unlikely in this study? If not, was all potential confounding appropriately adjusted for? Only in the case of no expected confounding would this item be considered as low risk of bias.
2. Was selection into the study unrelated to exposure (specifically for case-control studies) or unrelated to outcome (in case of cohort studies)? Specifically for case-control studies, were the controls sampled from the population that gave rise to the cases (or in other words, did the controls originate from the same studybase population)?
3. Is the exposure status well defined? Could participants have been misclassified as non-exposed or vice versa? If so, was this misclassification related to the outcome? Were data on exposure collected reliably, e.g. avoiding recall bias? Only studies with a well-defined exposure status based solely on information collected at time of the exposure are considered low risk of bias.
4. Were the critical co-exposures balanced across exposure groups? Or if not, were appropriate adjustment techniques used? Co-exposures refer to the usual care provided to participants. Studies have a low risk of bias if the intervention and comparator groups are implemented over short period, or if subsequent interventions are part of usual care or if the research question relates to the initiation of intervention regardless of adherence. Co-exposures refer to the usual care provided to participants.
5. Was outcome data and exposure status reasonably complete (>90% had data on exposure and outcome)? For cohort-type studies: If not, are the proportion of participants and reasons of missing data similar across exposures? For case-control studies: If not, are the proportion of participants and reasons of missing data similar across cases and controls? In the case of missing data, were appropriate statistical methods used?

For cohort-type studies: Was the outcome measured objectively? Were there any systematic errors in measurement of the outcome related to intervention received?

6. For case-control studies: Was case status based on objective criteria? Was case status applied without knowledge of the exposure status?
7. Were results selectively reported, meaning results reported on a particular (secondary) outcome, a particular (sensitivity) analysis or in a particular subset/subgroup?