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Comparison 1 Acyclovir versus placebo, Outcome 1 The number of individuals with oral lesions (8 days after the administration of the intervention).
Figures and Tables -
Analysis 1.1

Comparison 1 Acyclovir versus placebo, Outcome 1 The number of individuals with oral lesions (8 days after the administration of the intervention).

Comparison 1 Acyclovir versus placebo, Outcome 2 The number of individuals who developed new extraoral lesions after the administration of the intervention.
Figures and Tables -
Analysis 1.2

Comparison 1 Acyclovir versus placebo, Outcome 2 The number of individuals who developed new extraoral lesions after the administration of the intervention.

Comparison 1 Acyclovir versus placebo, Outcome 3 The number of individuals with eating difficulties (8 days after the administration of the intervention).
Figures and Tables -
Analysis 1.3

Comparison 1 Acyclovir versus placebo, Outcome 3 The number of individuals with eating difficulties (8 days after the administration of the intervention).

Comparison 1 Acyclovir versus placebo, Outcome 4 The number of individuals with drinking difficulties (8 days after the administration of the intervention).
Figures and Tables -
Analysis 1.4

Comparison 1 Acyclovir versus placebo, Outcome 4 The number of individuals with drinking difficulties (8 days after the administration of the intervention).

Comparison 1 Acyclovir versus placebo, Outcome 5 The number of individuals admitted to hospital after the administration of the intervention.
Figures and Tables -
Analysis 1.5

Comparison 1 Acyclovir versus placebo, Outcome 5 The number of individuals admitted to hospital after the administration of the intervention.

Table 1. Quality of included studies

Study ID

Sequence generation

Allocation concealment

Blinding

Intention‐to‐treat

Attrition

Amir 1997b

(A) Adequate: randomised table with a block size of 8

(A) Adequate

Participants (Yes), researchers (Yes), outcome assessment (Unclear)

Yes: the patients which were later excluded from the study, were included in the statistical analysis

Yes: the drop outs were described

Ducoulombier 1988

(A) Adequate: randomised table

(B) Unclear

Unclear: not described

No: there were 2 drop outs but no description was given

No: there were 2 drop outs but no description was given

Figures and Tables -
Table 1. Quality of included studies
Table 2. Results reported in the two included studies

Study ID

Results

Amir 1997b

Difference in median (95% CI) duration (in days) of clinical variables:
Oral lesions: (From 72: 5 (2.4 to 7.6)), (From 61: 6 (4.0 to 8.0)).
The time to healing was significantly shorter in the children receiving acyclovir (median: 4 days (range 2‐12)) than in those receiving placebo (median: 10 days (3‐15)). At the end of treatment on day 8, 2 out of 31 children in the acyclovir group still had oral lesions compared with 21 out of 30 in the placebo group.

Fever: (From 72: 1 (0.0 to 2.0)), (From 61: 2 (0.8 to 3.2)).
This disappeared significantly earlier in the acyclovir group (median 1 day) as opposed to placebo (median 3 days).

Extraoral lesions: (From 72: 3 (1.4 to 4.6)), (From 61: 5.5 (1.0 to 10.0)).
At enrolment one third of the children in each group had extraoral herpetic lesions. After commencing treatment, 13 of the patients from the placebo as opposed to none in the acyclovir group developed additional extraoral lesions. The median duration of extraoral lesions in the placebo group was reported as 5.5 days.

Hospital admission:
Before, inclusion in the study: Group 1: 2, Group 2: 3.
Among the rest of the children, after inclusion: Group 1: none, Group 2: 3 (2 to 3 days for rehydration (P = 0.11)).
At enrolment, 5 children (2 acyclovir, 3 placebo group) were admitted to hospital for rehydration. After commencement of treatment a further 3 children (placebo group) were admitted for 2 to 3 days for rehydration (P = 0.11).

Drooling: (From 72: 3 (1.4 to 4.5)), (From 61: 3.5 (2.0 to 5.0)).

Eating difficulties: (From 72: 3 (1.2 to 4.8)), (From 61: 3 (1.3 to 4.7)).
At enrolment all of the participants had difficulty with eating but by day 8 only 2 in the acyclovir group and 14 from the placebo group continued to have difficulties. The median duration of persisting difficulties in eating was 4 days in the acyclovir and 7 days in the placebo group.

Drinking difficulties: (From 72: 2 (0.3 to 3.7)), (From 61: 3 (1.1 to 4.9)).
At entry all the participants had difficulty with drinking but by day 8, only 1 child in the acyclovir and 9 in the placebo group were still experiencing difficulties. The median duration was 3 days (acyclovir) versus 6 days (placebo).

Viral shedding: (From 72: 4 (2.7 to 5.3)), (From 61: 4 (2.9 to 5.1)).

Compliance: Group 1: 29 received > 80% of treatment, the rest (50‐80%), Group 2: 24 received > 80% of treatment, the rest (50‐80%) (P = 0.117).

Side effects: Group 1: 2, Group 2: 2 mild gastrointestinal symptoms that resolved spontaneously after 24 to 48 hours without a change in the study treatment.

Ducoulombier 1988

Time to resolution of pain: Group 1 (1 day = 1, 2 days = 1, 3 days = 3, 4 days = 3, 5 days = 1, persistent = 0), Group 2 (1 day = 0, 2 days = 0, 3 days = 1, 4 days = 2, 5 days = 4, persistent = 2) (2 patients were not reported) (P < 0.05).
The trialists reported the time to resolution of pain but did not describe how they assessed pain or its severity. Considering the age of the participants, it is questionable whether they would be able to self report.

Time to resolution of hypersialorrhea (excessive drooling of saliva): Group 1 (1 day = 1, 2 days = 1, 3 days = 3, 4 days = 3, 5 days = 1, persistent = 0), Group 2 (1 day = 1, 2 days = 0, 3 days = 0, 4 days = 2, 5 days = 3, persistent = 3) (2 patients were not reported) (P < 0.05).

Anorexia (loss of appetite): Group 1: in 5 patients disappeared after 4 days, Group 2: in 4 patients disappeared after 5 days, 1 patient had persistent anorexia (comparable in 2 groups, P value not reported).
5 patients in the acyclovir group regained their appetite after 4 days, and 5 patients in the placebo group after 5 days. 1 patient continued to experience difficulties until the end of the treatment period. The trialists indicated that this outcome was comparable between the 2 groups but did not report a P value or any additional details.

General physical health: Group 1: 7 patients were fine from the beginning to the end of the treatment, Group 2: 5 patients were fine from the beginning to the end of the treatment (comparable in 2 groups, P value not reported).

Body temperature (time period to get to the normal temperature < 37 C): In the beginning of the study 9 children from Group 1 and 4 from Group 2 had fever and there was not significant different between the 2 groups to reach the normal temperature.
The trialists reported that at the beginning of the study 9 children from the acyclovir group and 4 from the placebo group had fever and that there was no significant difference between the 2 groups in the time taken to return to normal temperature, although no details were provided.

Physical symptoms: Group 1 and Group 2 had no statistically significant difference.
a) Labial lesions: persistent up to day 5 of the treatment in up to 50% of patients in both groups.
b) Lingual lesions: persistent up to day 5 of the treatment in up to 50% of patients in both groups.
c) Palatal lesions: disappeared in all of the patients.
d) Gingival lesions: mostly disappeared.
e) Buccal lesions: mostly disappeared.
f) Pharyngeal lesions: mostly disappeared.
g) Peribuccal lesions: disappeared in more than half of the cases before 5 days.

Cervical adenopathy: This was persistent in all of the patients in the placebo group and disappeared in 3 patients from the acyclovir group in first 4 days of the treatment.

Viral culture: Negative culture 7 from 8 patients (acyclovir group) and 3 from 5 patients (placebo group). 5 patients were unknown. 2 patients were not reported.

Tolerance and acceptability of the drug was described as satisfactory but it was unclear how this was assessed by the trialists.

Figures and Tables -
Table 2. Results reported in the two included studies
Comparison 1. Acyclovir versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 The number of individuals with oral lesions (8 days after the administration of the intervention) Show forest plot

1

72

Risk Ratio (M‐H, Fixed, 95% CI)

0.10 [0.02, 0.38]

2 The number of individuals who developed new extraoral lesions after the administration of the intervention Show forest plot

1

72

Risk Ratio (M‐H, Fixed, 95% CI)

0.04 [0.00, 0.65]

3 The number of individuals with eating difficulties (8 days after the administration of the intervention) Show forest plot

1

72

Risk Ratio (M‐H, Fixed, 95% CI)

0.14 [0.03, 0.58]

4 The number of individuals with drinking difficulties (8 days after the administration of the intervention) Show forest plot

1

72

Risk Ratio (M‐H, Fixed, 95% CI)

0.11 [0.01, 0.83]

5 The number of individuals admitted to hospital after the administration of the intervention Show forest plot

1

72

Risk Ratio (M‐H, Fixed, 95% CI)

0.14 [0.01, 2.67]

Figures and Tables -
Comparison 1. Acyclovir versus placebo