240 CHAPTER 3.2 group difference for adverse drug reactions and neither for the secondary endpoints of rehospitalization or death [19]. Implementation of medication advice was very low (approximately 15%), blinding was limited, and contamination risk was not completely eliminated due to individual-level instead of cluster randomization. Another cluster-RCT of 3,904 older adults with polypharmacy in general practices compared an electronic decision support tool for comprehensive medication review designed to de-prescribe inappropriate medications versus standard care [55]. After 24 months, there was no between-group difference for the composite endpoint of unplanned hospital admissions or death, although the per-protocol analysis favoured the intervention (OR 0.82, 95%CI=0.68 to 0.98). However, patients, physicians and research staff were not blinded, and outcomes were not independently adjudicated. In contrast to these two RCTs, OPERAM combined software-based pharmacotherapy optimization with direct contact between research physicians/pharmacists and hospital physicians. This may have contributed to greater implementation of recommendations compared to SENATOR and allowed the consideration of individual patient needs and preferences. Potential explanations for the lack of effect on drug-related hospital admission Although pharmacotherapy optimization reduced potentially inappropriate medication and led to no detriment to patient outcomes, there are several possible explanations for the lack of effect on drug-related hospital admissions in OPERAM. Firstly, the impact of a single timepoint pharmacotherapy optimization may not persist over a 1-year follow-up, during which multiple physician contacts may occur. Although we provided evidence-based recommendations on inappropriate prescribing to patients’ GPs, including reasons for stopping or starting drugs, the contacts with other physicians (e.g., specialists) over 1 year may have resulted in new potentially inappropriate medications or discontinuation of appropriate medications, which may have negated an intervention effect. Nevertheless, our point estimates are reassuring for a lack of detrimental effect on patient outcomes from primarily stopping inappropriate medications and showed a pattern favouring the intervention which may indicate that the effect was as intended, albeit weak. Secondly, the high mortality rate of the population approaching 20% at 12 months may have diluted benefits from pharmacotherapy optimization. Thirdly, implementation of recommendations (i.e., medication changes recommended by STRIP) at two months was suboptimal, although implementation of complex interventions is often lower in multi-centre trials (approximately 15% to 42%) [19,55] compared to some single centre trials (93%) [27]. The moderate implementation level in OPERAM was likely multifactorial. Multiple prescribers’ barriers to minimizing inappropriate prescribing have been identified [56]. Our intervention could address some of these barriers among attending hospital physicians and GPs; it improved prescriber awareness
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