Side effects were recorded individually and then categorised as being ‘significant’ or ‘minor’. A significant side effect was defined as a potentially life-threatening adverse reaction. Examples were mortality, inability to maintain an airway

or desaturations not corrected by head movements. Minor side effects were defined as any reported adverse events that were non-life-threatening. Examples of minor side effects were more difficult to subcategorise, principally due to an inconsistent use of terminology in studies. All have been reported. Data related to the effectiveness of the sedative were not collected. 4. Types of study: Allocation concealment, patient, operator or assessor blinding were not used as entry criteria for this review. Evidence was ranked according to its quality, and the ranking was as follows (highest first): Randomised controlled clinical trials of effectiveness Z-VAD-FMK datasheet and randomised controlled clinical trials looking at adverse outcomes Non-randomised studies. Prospective or retrospective observational studies (including case reports) Reference books and databases describing

adverse effects as listed in Chapter 14 of the Cochrane Review Handbook[6]. The search for RCTs was modelled on that used by Matharu and Ashley[7] in their effectiveness review in 2005. This version was used as the updated review Pembrolizumab excludes crossover trials. The search for any other non-randomised studies used a combination of controlled vocabulary and free text terms based on the search strategy as described in Chapter 14 of the Cochrane Handbook[6]. See Fig. 1 for Medline search, Fig. 2 for Embase search [MEDLINE (OVID), 1950 to November 2011 week 1; EMBASE (OVID) 1947–2011 November 8]. This was then supplemented by a further free text search as recommended in Chapter 14 of the Cochrane Handbook[6]. In addition, reference books and regulatory authorities were also searched for reports on oral midazolam using the website search engine and the free text term ‘midazolam’ (full list in Fig. 3)[8-11]. Specialist drug information databases were not searched due to subscription costs and as their usefulness

or additional yield have yet to be formally evaluated in the systematic review setting. The following journals were identified Janus kinase (JAK) as being important to be hand searched for this review: International Journal of Paediatric Dentistry, Pediatric Dentistry, Journal of American Dental Association, Anesthesia Progress. The journals were hand searched by the review authors for the period January 2000 to November 2011. The reference lists of all eligible trials were checked for additional studies. The search attempted to identify all relevant studies irrespective of language. Non-English papers were translated where possible. Results from these searches were combined together using Reference Manager (Thomson Corp, Carlsbad, CA, USA). The recommended adverse effects search terms as described by Loke et al.