Section (A) Are the results of the review valid?

Screening Questions 1. Did the trial address a clearly focused issue?

Yes. The authors attempted to evaluate the efficacy of two sustained release antibiotic regimens for the reduction of infection after third molar surgery (extraction): Pre-op amoxicillin/clavulanate 2000/125 mg vs post-op amoxicillin/clavulanate 2000/125 mg vs. placebo (5 day treatment). Outcomes of interest were Infection (purulent discharge in surgical site, pain, local abscess, increased heat, pyrexia, trismus, dental osteitis. All evaluated on days 1, 3, 7 post-op.

2. Was the assignment of patients to treatments randomised?

Allocation concealment is not mentioned and therefore an unclear risk. Also random sequence generation is mentioned as randomised, however the method of how it was generated has not been provided.

3. Were all of the patients who entered the trial properly accounted for at its conclusion?

Every patient was accounted for at conclusion.

Detailed questions 4. Were patients, health workers and study personnel ‘blind’ to treatment?

All were blinded.

5. Were the groups similar at the start of the trial?

Size of all four groups were identical (n = 75 for each group). The composition of each group was very similar except one group composed of a higher female population. Pre-op amoxicillin/clavulanate 2000/125 mg: 33 (M)/42 (F), mean age = 29.7 years post-op amoxicillin/clavulanate 2000/125 mg: 37 (M)/48 (F), mean age = 52 years placebo: 26 (M)/49 (F), mean age = 28.2 years Each group had a total of 75 extractions (1 extraction per patient)

6. Aside from the experimental intervention were the groups treated equally?

Yes. All groups were treated at one treatment centre and subject to the same inclusion/exclusion criteria.

Section (B) What are the results?

7. How large was the treatment effect?

Higher rate of infection was seen in placebo group (16%) vs. single dose prophylaxis (5.3%) vs. 5 day pre-emptive therapy (2.7%) (p = 0.006) meaning results were statistically significant. A significant result was seen in the correlation between the longer duration of surgery and rate of infection (p = 0.011) (although initially this was not an outcome of interest). Pre-emptive and pre-operative antibiotics vs. placebo saw a greater reduction of postoperative pain on day 3 (p = 0.0001) Overall pre-emptive therapy is better suited for more complex procedures (extraction including bone removal). Prophylaxis is more beneficial in simpler procedures.

8. How precise was the estimate of the treatment effect?

Details on CI were not included for results of the study; however they were provided for the reasoning behind why 75 patients were required in each study group in order to achieve a sufficient sample size (based on a previous pilot study with smaller samples sizes)

Section (C) Will the results help locally?

9. Can the results be applied in your context? (or to the local population?)

Results may not be generalisable to a whole general population. Patients were not treated in a general dental surgery, where most extractions take place. Patients did not comprise of the elderly, young children, immunocompromised patients or those at risk of IE. The mean age of patients across all three groups was in the late 20’s. A larger sample size would also be required.

10. Were all clinically important outcomes considered?

Yes, however the CI for each outcome considered was not provided (although p values were).

11. Are the benefits worth the harms and costs?

Results described above are statistically significant. Generally adverse events were seen more frequently in the pre-emptive antibiotic group and with greater effect compared to prophylaxis and placebo groups. Therefore the choice of antibiotic regimen should be carefully considered when judging the difficulty of extraction and the benefits of administration to each individual patient. With regards to cost, amoxicillin is relatively cheap in the UK but the risk of other complications such as microbial resistance may outweigh the benefit if it is to be routinely prescribed for an extraction procedure which is uncomplicated and of short duration.