Methods

Cross‐over randomised controlled trial

Participants

36 adults (22 women) with passive FI and structurally intact anal sphincters
Mean age 58 years (range 28 to 81)
Mean duration of faecal incontinence: 5 years (SD 4)
Characteristics of patients were comparable at baseline
Exclusion criteria: disruption of anal sphincter muscle on endoanal ultrasound examination, concomitant use of tricyclic or mono‐amine oxidase inhibitors, hypertension, aortic aneurysm or ischaemic heart disease, pregnancy, inflammatory bowel disease and surgically repairable sphincter damage.

Interventions

A: 10% phenylephrine gel
B: placebo gel (0.5 mL), both used anally twice a day
Length of treatment: 4 weeks (two four‐week treatment periods with a one‐week washout period)
Dose titration: the choice of 10% phenylephrine gel was based on previous pilot studies on healthy volunteers

Outcomes

Subjective cure: A: 0/36, B: 0/36
Subjective improvement in symptoms: A: 6/36, B: 2/36 [A: 28% versus B: 9% at the end of the first trial period]
Incontinence score (n, mean, SD): A: 18, 12.5 (3.4), B: 18, 12.6 (4.2) (no difference)
Adverse effects: A: 3/36, B: 0/36 (localised mild dermatitis, settled when drug stopped)
Maximum anal resting pressure (n, mean, SD): A: 18, 65 (21), B: 18, 54 (21) (no difference)
Anodermal blood flow (no change)

Notes

15 patients continued with loperamide during the study
Sample size calculation pre‐stated (16 patients required)
Suggestion of an interaction between treatment and placebo periods, possibly reflecting an insufficient washout period

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Randomisation was carried out by a pharmacist by means of computer generated random numbers"

Allocation concealment (selection bias)

Low risk

"The randomization code was kept in the hospital pharmacy and made known to the investigators only after analysis of the completed study."

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Repored as "double‐blind" trial but it is not specified who was blinded.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Repored as "double‐blind" trial but it is not specified who was blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No incomplete data

Selective reporting (reporting bias)

Unclear risk

Protocol not available

Was use of a cross over design appropriate?

Low risk

Yes

Is it clear that the order of receiving treatment was randomised?

Low risk

Used computer‐generated random numbers.

Can it be assumed that the trial was not biased from carry over effects?

Unclear risk

"4 weeks treatment periods separated by a 1 week washout period"

Methods

Cross‐over randomised controlled trial

Participants

12 adults (7 women) with FI after ileoanal pouch surgery for ulcerative colitis
Median age 44 years (range 29 to 67)
8 had nocturnal incontinence only, 4 had both diurnal and nocturnal incontinence
Exclusion criteria: active pouchitis, disruption of anal sphincter muscles on endoanal ultrasound examination, concomitant use of tricyclic or monoamine oxidase inhibitors, hypertension, ischaemic heart disease or aortic aneurysm.

Interventions

A: 10% phenylephrine gel
B: placebo gel (0.5 mL), both used anally twice a day
Length of treatment: 4 weeks (two four‐week treatment periods with a one‐week washout period)
Dose titration: the choice of 10% phenylephrine gel was based on previous pilot studies on healthy volunteers

Outcomes

Cure: A: 4/12, B: 0/12
Subjective improvement in symptoms: A: 6/12, B: 1/12
Incontinence score (28 day symptom score, n, mean, SD): A: 12, 12.2 (5.7), B: 12, 16.5 (4.4)
Adverse effects: A: 0/12, B: 0/12
Maximum anal resting pressure (n, mean, SD): A: 12, 89 (17), B: 12, 75 (14)
Anodermal blood flow (no difference)

Notes

8 patients continued with loperamide during the study
Suggestion of an interaction between treatment and placebo periods, possibly reflecting an insufficient washout period

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Random assignment was performed using random numbers generated by a scientific calculator, and the randomization code was kept in the hospital pharmacy and made known to the investigators only after analysis of the completed study"

Allocation concealment (selection bias)

Low risk

"Random assignment was performed using random numbers generated by a scientific calculator, and the randomization code was kept in the hospital pharmacy and made known to the investigators only after analysis of the completed study"

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Repored as "double‐blind" trial but it is not specified who was blinded.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Repored as "double‐blind" trial but it is not specified who was blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No incomplete data

Selective reporting (reporting bias)

Unclear risk

Protocol not available

Was use of a cross over design appropriate?

Low risk

Yes

Is it clear that the order of receiving treatment was randomised?

Low risk

"Random assignment was performed using random numbers generated by a scientific calculator, and the randomization code was kept in the hospital pharmacy and made known to the investigators only after analysis of the completed study"

Can it be assumed that the trial was not biased from carry over effects?

Unclear risk

"...........two four‐week treatment phases separated by a one‐week washout phase."

Methods

Randomised controlled trial

Participants

206 people (145 women) with at least weekly faecal incontinence associated with chronic rectal emptying (40% of patients had daily faecal incontinence for more than 2 years). 178 were available for analysis after the first week of treatment. Patients were aged 65 years or older and residents of long‐term care units.
Mean age: 85.3 years
Characteristics of patients were comparable at baseline but not given after losses to follow‐up

Interventions

A: 30 g per day of a single osmotic laxative (lactulose)
B: 30 g of an osmotic laxative (lactulose), along with daily glycerine suppository and a tap‐water enema once a week
Length of treatment: 8 weeks
Dose titration: no

Outcomes

Mean number of FI episodes per week (n, mean, SD): A: 61, 6 (2.9), B: 62, 6 (2.7) (P = 0.9 after 4 weeks)
Mean number of bedding and/or clothing changes per week (n, mean, SD): A: 61, 20 (4), B: 62, 19.5 (5.2) (P = 0.55 after 4 weeks)
Incidents of FI per day per participant: A: 0.85, B: 0.84
Incidents of soiled laundry per day per participant: A: 2.9, B: 2.8
Adverse effects: not reported.

Notes

Higher dropout rate in Group I than in Group II
Results not clearly reported
Number of 'responders' and 'non‐responders' were assessed only in Group II
No differences in subgroup analyses according to cognitive or mobility impairment, or between centres

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Reported as "prospective randomized study" but the method of sequence generation not specified

Allocation concealment (selection bias)

Unclear risk

Reported as "prospective randomized study" and it is not specified whether or not the allocation was concealed.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

"This study could be randomized but not blinded because outcomes were measured daily and because the treatment was provided by the nursing staff."

Blinding of outcome assessment (detection bias)
All outcomes

High risk

"This study could be randomized but not blinded because outcomes were measured daily and because the treatment was provided by the nursing staff."

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

No missing data, however 32 participants in Group I and 23 participants in Group II withdrew from the trial.

Selective reporting (reporting bias)

Unclear risk

Protocol not available

Was use of a cross over design appropriate?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Is it clear that the order of receiving treatment was randomised?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Can it be assumed that the trial was not biased from carry over effects?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Methods

Randomised controlled trial.

Participants

10 people (7 women) with passive faecal incontinence and low maximal resting anal pressure but with intact sphincters demonstrated on endoanal ultrasound scan
Median duration of incontinence: 2 years (range 1 to 7)
Groups comparable at baseline on maximal resting anal pressure (cross‐over)
Exclusion criteria: pregnant women, ischaemic heart disease, aortic aneurysm, uncontrolled hypertension, inflammatory bowel disease, other secondary causes of FI

Interventions

A: 0% gel (placebo containing no active ingredient)
B: 10% phenylephrine gel in identical coded foil tubes
C: 20% phenylephrine gel
D: 30% phenylephrine gel
E: 40% phenylephrine gel
Duration of treatment: 1 anal application per day, minimum 48 hours apart
Assessment: one and two hours after application

Outcomes

Maximal resting anal pressure: comparable at baseline on all study days
Maximal resting anal pressure: 7 increased, no change in 3 participants
D & E: maximal resting anal pressure increased to within normal range (P < 0.05 versus placebo group A)
B & C: maximal resting anal pressure increased but below normal range
Effect sustained for a median of 7 hours
Adverse effects: two people experienced a stinging/burning sensation immediately after application of phenylephrine gel, which settled within 20 minutes

Notes

Washout of 48 hours between daily doses

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

It is reported that "Gels were applied in a random order..................." however it is not specified how sequence was generated

Allocation concealment (selection bias)

Unclear risk

It is reported that "Gels were applied in a random order..................." however it is not specified if the allocation was concealed or no

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

It is reported that both the investigator and patients were unaware of the nature of each gel.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

It is not specified if the outcome was assessed by the investigator or someone else.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No missing data

Selective reporting (reporting bias)

Unclear risk

Protocol not available

Was use of a cross over design appropriate?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Is it clear that the order of receiving treatment was randomised?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Can it be assumed that the trial was not biased from carry over effects?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Methods

Cross‐over randomised controlled trial

Participants

11 adults
Dropouts: 1 (diarrhoea on placebo, as participants had to stop normal anti‐diarrhoeal drugs)
Inclusion: patients with ileoanal pouches (9 J, 2 W) 9 to 48 months after ileostomy closure (median 27); 8 for ulcerative colitis, 2 for familial adenomatous polyposis; 8 men, 3 women
Exclusion: not specified
Age: 23 to 50 years (median 38)

Interventions

Initial 2 day drug‐free washout period
A (10): loperamide oral capsules 4 mg 3x/day and placebo suppositories for 5 days in first 4 participants, then for 7 days in the remaining 6
Washout phase with placebo oral and suppository treatment between first and second arms
B (10): loperamide suppositories 2 mg x3 in hard fat and placebo oral capsules

Outcomes

Mean stool frequency stated to be significantly lower with oral loperamide (Group A) compared with suppository (Group B, P < 0.02) or placebo washout phase (P < 0.05)
No significant difference between suppository (Group B) or placebo washout phases

Notes

No useable data (graphical form only)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

It is reported that the "Subjects were randomized........", however, method of sequence generation not specified.

Allocation concealment (selection bias)

Unclear risk

Not specified

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

"Subjects were blinded to the contents of their medication in all three phases. The investigators were blinded to the contents in the first and third phases."

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No incomplete data

Selective reporting (reporting bias)

Unclear risk

Protocol not available

Was use of a cross over design appropriate?

Low risk

The design seems to be appropriate, however information pertaining to sequence generation and allocation concealment are not provided, and the washout period seems to be short.

Is it clear that the order of receiving treatment was randomised?

Unclear risk

Not specified

Can it be assumed that the trial was not biased from carry over effects?

High risk

"2‐day drug‐free washout period"

Methods

Cross‐over randomised controlled trial.

Participants

10 adults (7 men and 3 woman)
Dropouts:
Inclusion: obese people on orlistat 120 mg 3x/day; BMI > 30; negative pregnancy test
Exclusion: elderly (age > 55 years); postnatal women; continence problems; gastrointestinal disease; psychological problems; abnormal laboratory results
Age: mean 46 years (range 27 to 54)
BMI: 35.7 (30.2 to 43.6)

Interventions

A: loperamide 2 mg + placebo x 2
B: loperamide 2 mg x2 (= 4 mg) + placebo x 1
C: loperamide 2 mg x3 (= 6 mg) + no placebo
Each block of active treatment for 2 weeks
Washout: 2 weeks between each block

Outcomes

No effect on stool frequency
Trend for increased stool consistency from median (IQR) score 0.7 (0.5 to 0.9) with placebo to 0.4 (0.3 to 0.6) with 6 mg dose (0 = all hard, 1 = all liquid)
Continence problems (fecal spotting and incontinence) reduced with loperamide vs placebo, P < 0.05
Significant positive dose‐response relationship with increasing dose of loperamide (reduced FI with 2 mg dose, and almost no FI with 4 mg and 6 mg doses)
Adverse effects: none (specifically no severe constipation with the highest doses)

Notes

Study aim was to reduce the adverse effects of orlistat treatment for obesity (oily stools, increased faecal frequency and urgency and 'fecal spotting' (= faecal incontinence) in order to increase compliance with orlistat
No useable data

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"The hospital pharmacy dispensed medication according to a computer generated randomization list."

Allocation concealment (selection bias)

Low risk

"The sequence was concealed until the study was completed".

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Reported as "double‐blind study", however it is not specified who was blinded.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Reported as "double‐blind study", however it is not specified who was blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No incomplete outcome data

Selective reporting (reporting bias)

Unclear risk

Protocol not available

Was use of a cross over design appropriate?

Low risk

Each participant received placebo and two of the three doses of loperamide for 2 weeks, each separated by a 2‐week washout. The sequence was concealed until the study was completed.

Is it clear that the order of receiving treatment was randomised?

Low risk

"The hospital pharmacy dispensed medication according to a computer generated randomization list."

Can it be assumed that the trial was not biased from carry over effects?

Low risk

Each participant received placebo and two of the three doses of loperamide for 2 weeks, each separated by a 2‐week washout.

Methods

Cross‐over randomised controlled trial.

Participants

30 adults (8 women) with ileoanal pouches (16 handsewn and 14 stapled), performed for ulcerative colitis. Groups combined for analysis
Median age: 38 years (range 26 to 61)
Exclusion criteria: not specified

Interventions

A: loperamide 4 mg three times a day
B: placebo
Duration of treatment: 8 day treatment periods with 7 day washout period.
Dose titration: no

Outcomes

Number experiencing soiling, day: A: 3/28, B: 7/28; night: A: 1/28, B: 11/28
Number using pads, day: A: 1/28, B: 3/28; night: A: 1/28, B: 6/28
Defecation frequency (n, mean, SD): A: 28, 4.24 (1.86), B: 28, 6.43 (1.99)
Anal canal resting pressure, mm Hg (n, mean, SD): A: 28, 62 (16), B: 28, 55 (9)
Anal canal maximum squeeze pressure, mm Hg, (n, mean, SD): A: 28, 223 (82), B: 28, 219 (93)
Pouch volumetry and contractility.
Sensory threshold, rectal balloon distension, cm water, for 'sensation of filling' and 'defecation urge' (n, mean, SD): A: 28, 30 (12), B: 28, 27 (15)
Recto/pouch ‐ anal reflex inhibition on distension.
No adverse effects.

Notes

Patients were asked to keep to usual meal times and diet.
Data from two groups combined, and converted from medians and 95% CIs to means and SDs.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not specified

Allocation concealment (selection bias)

Unclear risk

Not specified

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Reported as "double blinded" and used "identical capsule" therefore participants must be blinded. Not sure about personnel

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No complete data

Selective reporting (reporting bias)

Unclear risk

Protocol not available

Was use of a cross over design appropriate?

Low risk

Seems appropriate with seven days washout period in between.

Is it clear that the order of receiving treatment was randomised?

Unclear risk

Method of randomisation not specified

Can it be assumed that the trial was not biased from carry over effects?

Low risk

There was seven days washout period

Methods

Cross‐over randomised controlled trial

Participants

15 people (14 women) with chronic diarrhoea and FI
Range of severity of FI: once a day to once a month
Mixed aetiology of diarrhoea
Age: 31 to 70 years
Exclusion criteria: none specified

Interventions

A: diphenoxylate (2.5 mg) plus atropine sulfate (25 mcg)
B: placebo
Length of treatment: 3 days, with one day of washout
Dose: 1 or 2 tablets, four times a day
Dose titration: not clearly reported. The first four patients were treated with two tablets every six hours (standard treatment). However, the 4th patient experienced abdominal pain and the dose was reduced in subsequent patients from 2 to 1 tablet every six hours.

Outcomes

Failure rate (number not continent): A: 0/15, B: 3/15
Failure to improve (in stool weight and frequency): A: 3/15, B: 3/15
Stool frequency (n, mean, SD): A: 15, 2.6 (2.7), B: 15, 4.9 (3.1)
Stool weight (n, mean, SD): A: 15, 256 (333), B: 460 (150)
Anal canal resting pressure, mm Hg (n, mean, SD): A: 15, 41 (23), B: 15, 39 (19)
Anal canal maximum squeeze pressure, mm Hg, (n, mean, SD): A: 15, 94 (68), B: 15, 96 (68)
Duration of squeeze, seconds, (n, mean, SD): A: 15, 87 (128), B: 15, 86 (128)
Sensory threshold, rectal balloon distension, cm water: 15, 12 (12), B: 15, 31 (62)
Saline retention (continence) test, mL water: A: 15, 492 (461), B: 15, 486 (445)
Adverse effects: not reported.

Notes

Patients were admitted to hospital and given a standardised diet

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Reported as "patients were randomized in a double‐blind fashion", however method of sequence generation not specified.

Allocation concealment (selection bias)

Unclear risk

Not specified.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

"Neither the patients, the laboratory personnel, nor the physicians in charge knew when the patients were lomotil or when they were on placebo until the code was broken after the experiment was completed".

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

"Neither the patients, the laboratory personnel, nor the physicians in charge knew when the patients were lomotil or when they were on placebo until the code was broken after the experiment was completed".

Incomplete outcome data (attrition bias)
All outcomes

High risk

reported data of only those participants who completed the trial as reported "data on this 4th patient are not included ion this paper...........". The excluded patient had "severe abdominal discomfort" the cause of which is not specified.

Selective reporting (reporting bias)

Unclear risk

Protocol not available

Was use of a cross over design appropriate?

Low risk

Seems appropriate

Is it clear that the order of receiving treatment was randomised?

Unclear risk

Not specified

Can it be assumed that the trial was not biased from carry over effects?

High risk

No washout period

Methods

Cross‐over randomised controlled trial

Participants

17 patients (4 women) with 'J' configuration ileoanal pouches 1 to 4 months after closure of diverting ileostomy (8 patients with ulcerative colitis and 9 with familial adenomatous polyposis)
Mean age 34 years (range 21 to 45, SD 6.51)
Exclusion criteria: none specified

Interventions

A: sodium valproate 400 mg
B: placebo
Dose: four times a day
Length of treatment: two one‐week treatment periods with a three day washout period
Dose titration: no

Outcomes

Number with FI (soiling): A: 3/17, B: 10/17
Stool frequency (n, mean SD): A: 17, 5.98 (2.97), B: 17, 9.65 (4.1)
Adverse effects: A: 6 people experienced nausea and 2 abdominal pain (8/17), B: 0/17
Perianal skin irritation due to contact with faeces: A:3/17, B: 9/17
Anal canal resting pressure, mm Hg (n, mean, SD) (at 7 days): A: 17, 63.6 (12.4), B: 17, 42.5 (8.9)
Anal canal motility (amplitude, frequency and voluntary contractions)

Notes

Sodium valproate has contractile effects on the internal anal sphincter
Patients ate a controlled hospital diet and took no other drugs

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not specified. Reported as "The valproate sodium and placebo series were carried out in random order"

Allocation concealment (selection bias)

Unclear risk

Not specified

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not specified

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not specified

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No incomplete data

Selective reporting (reporting bias)

Unclear risk

Protocol not assessed

Was use of a cross over design appropriate?

Unclear risk

Seems appropriate

Is it clear that the order of receiving treatment was randomised?

Unclear risk

Not specified

Can it be assumed that the trial was not biased from carry over effects?

Low risk

There was a 3‐day washout period

Methods

Randomised controlled trial

Participants

Adults patients > 21 years old who, having undergone coloproctectomy with ileoanal anastomosis and J‐shaped ileal reservoir, presented with nocturnal faecal incontinence

Exclusion criteria: associated anal pathology, active pouchitis, stenotic ileoanal anastomosis, concomitant treatment with loperamide, monoaminoxidase inhibitors and/or tricyclic antidepressants, pregnancy, narrow angle glaucoma, uncontrolled arterial hypertension/coronary disease/cardiac arrhythmias/aortic aneurysm, epilepsy

37 patients initially identified from 98 interviews

Reasons for non ‐ inclusion/withdrawal: 9 with associated anal pathology or intercurrent illness, 9 did not complete previous evaluations, 4 refused to participate, 3 did not complete treatment

12 participants included in final analysis

Group A: 5 (2 men, 3 women. Mean age: 49.0 [Range 27‐62])

Group B: 7 (6 men,1 woman. Mean age: 38.7 [Range: 24‐63])

Interventions

A: Cream with active ingredient (10% phenylephrine)

B: Placebo cream

0.5 mg cream to be applied digitally around anal margin by patients before going to bed

Length of treatment: 1 month (number of days unclear). A faecal incontinence diary was kept for 21 days before treatment and during the treatment month.

All patients received 3.5g Plantago ovata thereby guaranteeing minimal fibre intake. Liquid intake restricted to 1.5 L/day

Outcomes

Occurence of faecal incontinence during treatment; median (range)

Group A: 5.4 (0‐14) Group B: 9 (0‐19)

Notes

9 patients with ulcerative colitis (Group A; 5 Group B; 4,). 3 patients previously operated for Familial Adenomatous Polyposis (all Group B). Inconsistent with exclusion criteria of the trial (associated anal pathology).

Discrepancy between text and table: texts states 3 men in group A whereas table states 2 men

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

'Fueron randomizados en dos grupos (A) y (B), utilizando la técnica de muestreo en bloque'

'They were randomised into two groups (A) and (B), using the technique of block sampling'

Allocation concealment (selection bias)

Unclear risk

None mentioned

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Technique not mentioned

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Technique not mentioned

Incomplete outcome data (attrition bias)
All outcomes

High risk

Two participants in Group B and 1 in Group A did not complete treatment, these results were not included in final analysis

Selective reporting (reporting bias)

High risk

Results of two participants not completing trial not reported

Was use of a cross over design appropriate?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of 'Risk of bias' assessment is not applicable and would be judged as low risk.

Is it clear that the order of receiving treatment was randomised?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of 'Risk of bias' assessment is not applicable and would be judged as low risk.

Can it be assumed that the trial was not biased from carry over effects?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of 'Risk of bias' assessment is not applicable and would be judged as low risk.

Methods

Cross‐over randomised controlled trial (three arms)

Participants

30 patients with persistent (chronic) diarrhoea for at least 3 months (definition of diarrhoea included urgency and faecal incontinence). Diagnoses included irritable bowel, Crohn's disease, after gastric surgery, ulcerative colitis, diabetes
Daily stool frequency at baseline: 4.9 (SEM 0.4) (range 1 to 9 times)
Previous treatment: codeine (5); loperamide (10); diphenoxylate (2)

Interventions

A: loperamide hydrochloride (2 mg)
B: codeine phosphate (45 mg)
C: diphenoxylate (5 mg) with atropine sulfate (0.025 mg)
Length of treatment: each drug for 4 weeks

Outcomes

Number of people with FI: A: 2/25, B: 3/25, C: 6/25
Per cent of stools that were solid: A: 68%, B: 58%, C: 36% (P < 0.01)
Stool frequency (n, mean, SEM): A: 15, 1.8 (0.3), B: 15, 1.9 (0.3), C: 15, 1.9 (0.3)
Faecal urgency: A: 3/16, B: 4/17, C: 9/17 (P < 0.05 for C versus A and B)
Adverse effects (abdominal pain, central effects, headache): A: 22 in 10/25 participants, B: 29 in 12/25, C: 39 in 12/25 (P < 0.05 for A versus C)
Adverse effects causing withdrawal from one arm (poor control, abdominal pain, vomiting, unwell, constipation): A: 4/25, B: 4/25, C: 5/25
Preference for treatment: A: 8/25, B: 7/25, C: 5/25, no preference 5/25

Notes

Not clear how many patients suffered from faecal incontinence at baseline.
Patients were instructed to increase the daily dose gradually until control was achieved or side effects became intolerable (but outcomes from last 3 weeks of treatment, after treatment stabilised)
Pre‐trial and between‐treatments washout periods were not included because of the relatively short half‐life of the drugs used and patients would not be able to tolerate a drug‐free week

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not specified

Allocation concealment (selection bias)

Unclear risk

Not specified

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Reported as "double blinded" and used "identical capsule" therefore participants must be blinded. Not sure about personnel

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not specified

Incomplete outcome data (attrition bias)
All outcomes

High risk

5 patients failed to attend the clinic regularly and withdrew early in the study. Ten further patients out of remaining 25 patients failed to complete the treatment period for one or more drugs

Selective reporting (reporting bias)

Unclear risk

Protocol not available

Was use of a cross over design appropriate?

Low risk

Seems appropriate

Is it clear that the order of receiving treatment was randomised?

Unclear risk

Not stated

Can it be assumed that the trial was not biased from carry over effects?

High risk

Patients were instructed to increase the daily dose gradually until control was achieved or side effects became intolerable (but outcomes from last 3 weeks of treatment, after treatment stabilised)
Pre‐trial and between‐treatments washout periods were not included because of the relatively short half‐life of the drugs used and patients would not be able to tolerate a drug‐free week

Methods

Randomised controlled trial

Participants

35 patients with low anterior resection with rectal cancer were recruited. 6 participants withdrew and the results were reported of 29 participants; 17 in the treatment group and 12 in the placebo group.All participants had anal incontinence of solid or liquid stools or gas and experienced failure of other treatments with anti‐diarrhoeal agents or biofeedback

Exclusion criteria were pregnancy, Ischaemic heart disease, uncontrolled hypertension, aortic aneurysm, treatment with monoamine oxidase inhibitors or tricyclic antidepressants, surgically reparable external sphincter injury, inflammatory bowel disease, or any other
disorder known to cause secondary anal incontinence.

Interventions

A: 30% Phenylephrine (3 g of Phenylephrine HCl in 7 g of white petrolatum) gel

B: Identical placebo gel

Length of treatment: 0.5 mL of gel was applied topically to the anal margin twice daily for 4 weeks,

Outcomes

Anal incontinence evaluated with Faecal Incontinence Severity Index (FISI)

A (n = 17)= Baseline: 32.5(14.5); After: 32.3(14.7) P = 0.940

B (n = 12)= Baseline: 32.1 (11.2); After: 32.4(14.4) P = 0.626

Quality of life assessed with Faecal Incontinence Quality of life (FIQL) scale and included the following domains: lifestyle, coping, depression and embarrassment

Lifestyle:

A (n = 17)= Baseline: 2.9(0.8); After: 2.9(1.0) P = 0.801

B (n = 12)= Baseline: 2.7(0.5); After: 3.0(0.8) P = 0.269

Coping:

A (n = 17)= Baseline: 2.5(0.9); After: 2.8(0.9) P = 0.110

B (n = 12)= Baseline: 2.5(0.5); After: 2.8(0.5) P = 0.119

Depression:

A (n = 17)= Baseline: 3.2(0.7); After: 3.2(0.8) P = 0.415

B (n = 12)= Baseline: 3.1(0.5); After: 3.2(0.5) P = 0.554

Embarrassment:

A (n = 17)= Baseline: 2.7(0.7); After: 3.0(0.7) P = 0.090

B (n = 12)= Baseline: 2.7(0.6); After: 2.6(0.8) P = 0.855

Manometry:

Resting pressure (mmHg):

A (n = 17)= Baseline: 30.0(12.3); After: 27.3(12.7) P = 0.362

B (n = 12)= Baseline: 32.6(14.2); After: 27.2(15.0) P = 0.306

Squeezing pressure (mmHg):

A (n = 17)= Baseline: 143.3(60.5); After: 160.4(76.9) P = 0.083

B (n = 12)= Baseline: 152.6(86.5); After: 147.1(76.5) P = 0.625

Sustained duration (s):

A (n = 17)= Baseline: 41.9(24.5); After: 44.9(48.3) P = 0.848

B (n = 12)= Baseline: 39.6(24.4); After: 32.8(14.4) P = 0.187

Sphincter length (cm):

A (n = 17)= Baseline: 3.2(0.9); After: 3.4(0.8) P = 0.368

B (n = 12)= Baseline: 3.5(0.8); After: 3.4(0.8) P = 0.743

High pressure zone (cm):

A (n = 17)= Baseline: 2.4(2.1); After: 1.9(0.5) P = 0.378

B (n = 12)= Baseline: 2.1(0.9); After: 2.3(0.9) P = 0.556

Complications:

Dermatitis reaction: A = 5/17; B = 1/12

Palpitation: A = 0/17; B = 1/12

Headache: A = 2/17; B = 0/12

Notes

Not clear how many patients suffered from faecal incontinence at baseline.
Patients were instructed to increase the daily dose gradually until control was achieved or side effects became intolerable (but outcomes from last 3 weeks of treatment, after treatment stabilised)
Pre‐trial and between‐treatments washout periods were not included because of the relatively short half‐life of the drugs used and patients would not be able to tolerate a drug‐free week

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"A one‐to‐one randomization code was derived by the pharmacy trials coordinator using a computer‐generated random number sequence"

Allocation concealment (selection bias)

Low risk

"The randomization code was kept in the hospital pharmacy and made known to the investigators only after the study was completed".

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

It is mentioned that the trial was "double blind" and it is also reported that "The placebo and phenylephrine gel were identical in appearance and texture and were supplied in identical containers" therefore it seems that the participants and personnel must be blinded although not specifically stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not specified

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

No incomplete data although 6 participants (2 from the intervention and 4 from the placebo arm) withdrew from the study due to poor compliance

Selective reporting (reporting bias)

Unclear risk

Protocol not available.

Was use of a cross over design appropriate?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Is it clear that the order of receiving treatment was randomised?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Can it be assumed that the trial was not biased from carry over effects?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Methods

Randomised controlled trial

Participants

44 patients with faecal incontinence were included.

All participants were women aged 18 years or over.

Interventions

A: Zinc‐aluminium ointment
B: Placebo ointment

Duration of treatment: Applied on the anal canal mucosa 3 times daily over 4 weeks.

Outcomes

Wexner Faecal Incontinence Score reported before and after the treatment

A (n = 24): Before: 16.6 (6‐20); After: 8.5 (0‐11) P < 0.001

B (n = 20): Before: 16.7 (5‐18); After: 13.1(5‐17) P = 0.02

There was a significant difference in the final scores favouring the treatment group (P = 0.001)

For Quality of life "Fecal Incontinence Quality of Life (FIQL) score" was used which included the following parameters: lifestyle, conduct, embarrassment and depression.

Lifestyle:

A (n = 24): Baseline: 2.49(1.06); After: 3.58(1.18) P < 0.001

B (n = 20): Baseline: 2.50(1.01); After: 2.55(1.03) P = 0.151

Conduct:

A (n = 24): Baseline: 2.19(1.02); After: 3.12(1.16) P < 0.001

B (n = 20): Baseline: 2.17(0.91); After: 2.37(1.13) P = 0.104

Embarrassment:

A (n = 24): Baseline: 1.54(0.82); After: 2.5(1.32) P < 0.001

B (n = 20): Baseline: 1.56(0.74); After: 1.76(0.84) P = 0.043

Depression:

A (n = 24): Baseline: 2.51(1.01); After: 3.48(1.17) P = 0.001

B (n = 20): Baseline: 2.46(1.02); After: 2.71(1.13) P = 0.093

The quality of life score increased in both groups but more in the treatment group in all the parameters.

Adverse effects/ complications: A = 0/24; B = 0/20

Notes

It is mentioned that the inclusion criteria were faecal incontinence, minimal sphincter disruption on anal endosonography and it is also stated that "aluminium ointment is effective in the treatment of anal fissure" therefore it seems that all the patients had anal fissure although not specifically stated.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Reported as "randomized trial" however method of sequence generation not specified

Allocation concealment (selection bias)

Unclear risk

Reported as "randomized trial" however method of allocation concealment not specified

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Reported as "double‐blind" however it is not specifically mentioned who was blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Reported as "double‐blind" however it is not specifically mentioned who was blinded

Incomplete outcome data (attrition bias)
All outcomes

High risk

Earlier it is mentioned that "six were lost to study" but later on it is reported that "one in the treatment group and four in the placebo group withdrew at the beginning of the study" i.e. five patients. They have not specified to which group the sixth patient belonged. Reasons for withdrawal also not reported.

Selective reporting (reporting bias)

Unclear risk

Protocol not available

Was use of a cross over design appropriate?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Is it clear that the order of receiving treatment was randomised?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Can it be assumed that the trial was not biased from carry over effects?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Methods

Cross‐over randomised controlled trial

Participants

26 patients (16 women) with chronic diarrhoea and FI
Heterogeneous group of patients with diarrhoea due to irritable bowel syndrome (n = 11), Crohn's disease (n = 2), ulcerative colitis (n = 1), diabetes mellitus (n = 2) and others including a group who were undiagnosed despite extensive tests
Mean age 45 years (range 24 to 82)
Exclusion criteria: none specified

Interventions

A: loperamide 4 mg three times a day
B: placebo
Length of treatment: two one‐week treatment periods
Washout period: not specified
Dose titration: no

Outcomes

Episodes of FI per week (n, mean number, range): A: 26, 0.6 (0 to 6), B: 26, 0.9 (0 to 6), P < 0.01
Improvement (number having fewer incontinence episodes): A: 7/26, B: 2/26
Episodes of faecal urgency per week (n, mean number, range): A: 26, 1.52 (0 to 7), B: 26, 5.3 (0 to 27), P < 0.001
Improvement (number having fewer episodes of faecal urgency): A: 19/26, B: 3/26
Bowel movements per week (n, mean, range): A: 26, 11 (1 to 44), B: 26, 17 (0 to 54), P < 0.001
24‐hour stool weight (n, mean g, range): A: 26, 102 (0 to 467), B: 26, 186 (0 to 466), P < 0.001
Per cent unformed stool per week (mean %, range): A: 40% (0 to 100), B: 57% (0 to 100), P < 0.001
Adverse effects (all mild): A: 18/26, B: 1/26 (constipation 11; abdominal pain 2; nausea and vomiting 3; exacerbation of diarrhoea 4)
Anal canal resting pressure (n, mean cm water, SD): A: 26, 84 (31), B: 26, 73 (31), P < 0.05
Anal canal maximum squeeze pressures: increased (but still below normal range) by loperamide only in the 17 participants who could not retain rectal saline. Within normal range in the 9 participants who could retain saline
Saline continence test (volume (mL water) at which first leak occurs, n, mean, SEM): A: 17, 950 (110), B: 17, 510 (100), P < 0.005
Recovery of rectoanal inhibitory reflex improved by loperamide (P < 0.05)
Rectal compliance enhanced by loperamide

Notes

Some data only presented graphically, data calculated by approximate measurement
Data analysed using Wilcoxon's rank sum test for paired data, and Student's t test for paired data

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not specified

Allocation concealment (selection bias)

Unclear risk

Not specified.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

It is stated that "Neither the patient, physician, or technician was aware of the preparation taken during the week. Finally, the technician who performed the objective tests was, in most instances, unaware of the subjective improvement of the patient during the previous week"

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

It is stated that "Neither the patient, physician, or technician was aware of the preparation taken during the week. Finally, the technician who performed the objective tests was, in most instances, unaware of the subjective improvement of the patient during the previous week"

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No incomplete data

Selective reporting (reporting bias)

Unclear risk

Protocol not available however, all the outcomes mentioned in the method section were reported

Was use of a cross over design appropriate?

Low risk

Seems appropriate

Is it clear that the order of receiving treatment was randomised?

Unclear risk

Not stated

Can it be assumed that the trial was not biased from carry over effects?

High risk

No washout period

Methods

Randomised controlled trial

Participants

87 patients admitted to a geriatric unit
Exclusion criteria: none specified

Interventions

A: Osmotic laxative (lactulose) 15 mL
B: 'no‐treatment' control group
Length of treatment: 21 days

Outcomes

Number of days when help required from nurses (n/N total trial days): A: 283/801, B: 322/724, P < 0.05
Number of days when > 20 minutes help required: A: 20/801, B: 33/724
Total number of soiled items (n/N participants): A: 154/44, B: 332/43, P < 0.01
Number of days with soiled linen (n/N total trial days): A: 92/801, B: 164/724, P < 0.01
No side effects reported

Notes

Concealment of allocation possibly inadequate
Characteristics of patients and comparability of intervention groups at baseline not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of sequence generation not specified

Allocation concealment (selection bias)

Unclear risk

Not specified

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

High risk

30 participants (14 in the treatment group and 16 in the 'no‐treatment' group) were discharged early and did not complete the full trial period

Selective reporting (reporting bias)

Unclear risk

Protocol not available

Was use of a cross over design appropriate?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Is it clear that the order of receiving treatment was randomised?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Can it be assumed that the trial was not biased from carry over effects?

Low risk

This is a randomised controlled trial and not a cross‐over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Methods

Cross‐over randomised controlled trial

Participants

11 patients (8 women) with chronic diarrhoea and FI
Median age: 56 years (range 44 to 77)
Inclusion criteria: chronic diarrhoea; FI more than 1x/week; severe urgency at least 3x/week; negative screening for infection, faecal fat and occult blood; normal sigmoidoscopy
Exclusion criteria: large volume diarrhoea (> 500 mL/24 hours); passive FI (anal seepage)

Interventions

A: Loperamide oxide 4 mg twice daily
B: placebo
Length of treatment: two one‐week treatment periods with one‐week washout period before and after each arm
Dose titration: no

Outcomes

Number of people cured (no diarrhoea or incontinence in 24 hours): A: 7/11, B: 3/11, P < 0.05
Number of people improved (stool consistency better): A: 9/11, B: 3/11
Frequency of defecation (number of bowel movements per day) (n, mean, SD): A: 11, 1.43 (1), B: 11, 2 (1), P < 0.02
Proportion of days with formed stools (%, SD): A: 67% (39), B: 34% (31), P < 0.02
Stool weight, g (n, mean, SD): A: 11, 282 (212), B: 11, 423 (163), P = 0.11
Incontinence episodes
Visual analogue (scale‐rated severity of FI) (n, mean, SD): A: 11, 26 (36), B: 11, 43 (37), P = 0.12
Adverse events: A: 6/11, B: 3/11 (constipation, abdominal pain, nausea and vomiting, headache)
Whole gut transit time (n, mean, SD): A: 11, 61 (13), B: 11, 39 (15), P < 0.001
Orocaecal gut transit time (n, mean, SD): A: 11, 296 (103), B: 11, 282 (121)
Anal canal resting pressure, mm Hg (n, mean, SD): A: 11, 76 (40), B: 11, 69 (35)
Anal canal maximum squeeze pressure, mm Hg (n, mean, SD): A: 11, 163 (86), B: 11, 155 (85)
Saline retention (continence) test, mL water (n, mean, SD): A: 11, 223 (274), B: 11, 150 (208)
Recto‐anal inhibitory reflex.

Notes

Heterogeneous disease groups (9 with irritable bowel syndrome, 1 with post‐gastrectomy diarrhoea and one with post‐cholecystectomy diarrhoea)
Normal range of mean wet stool weight = 57 to 100 g/day

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not specified

Allocation concealment (selection bias)

Unclear risk

Not specified

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Reported as "double‐blind study", however it is not specified who was blinded.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Reported as "double‐blind study", however it is not specified who was blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No missing data

Selective reporting (reporting bias)

High risk

it is reported that "the 24‐h faecal output (0800 h to 0800 h) was collected on days 4, 5, and 6 of each treatment week, and the net wet, consistency and dry weight were recorded", however the results are not reported for days 4 and 5 and only reported for day 6.

Was use of a cross over design appropriate?

Low risk

seems appropriate

Is it clear that the order of receiving treatment was randomised?

Unclear risk

Not reported

Can it be assumed that the trial was not biased from carry over effects?

Low risk

There was a washout period of 1 week