Rankin Audrey, Cadogan Cathal A, Patterson Susan M, Kerse Ngaire, Cardwell Chris R, Bradley Marie C, Ryan Cristin, Hughes Carmel
School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland, UK, BT9 7BL.
Cochrane Database Syst Rev. 2018 Sep 3;9(9):CD008165. doi: 10.1002/14651858.CD008165.pub4.
Inappropriate polypharmacy is a particular concern in older people and is associated with negative health outcomes. Choosing the best interventions to improve appropriate polypharmacy is a priority, hence interest in appropriate polypharmacy, where many medicines may be used to achieve better clinical outcomes for patients, is growing. This is the second update of this Cochrane Review.
To determine which interventions, alone or in combination, are effective in improving the appropriate use of polypharmacy and reducing medication-related problems in older people.
We searched CENTRAL, MEDLINE, Embase, CINAHL and two trials registers up until 7 February 2018, together with handsearching of reference lists to identify additional studies.
We included randomised trials, non-randomised trials, controlled before-after studies, and interrupted time series. Eligible studies described interventions affecting prescribing aimed at improving appropriate polypharmacy in people aged 65 years and older, prescribed polypharmacy (four or more medicines), which used a validated tool to assess prescribing appropriateness. These tools can be classified as either implicit tools (judgement-based/based on expert professional judgement) or explicit tools (criterion-based, comprising lists of drugs to be avoided in older people).
Two review authors independently reviewed abstracts of eligible studies, extracted data and assessed risk of bias of included studies. We pooled study-specific estimates, and used a random-effects model to yield summary estimates of effect and 95% confidence intervals (CIs). We assessed the overall certainty of evidence for each outcome using the GRADE approach.
We identified 32 studies, 20 from this update. Included studies consisted of 18 randomised trials, 10 cluster randomised trials (one of which was a stepped-wedge design), two non-randomised trials and two controlled before-after studies. One intervention consisted of computerised decision support (CDS); and 31 were complex, multi-faceted pharmaceutical-care based approaches (i.e. the responsible provision of medicines to improve patient's outcomes), one of which incorporated a CDS component as part of their multi-faceted intervention. Interventions were provided in a variety of settings. Interventions were delivered by healthcare professionals such as general physicians, pharmacists and geriatricians, and all were conducted in high-income countries. Assessments using the Cochrane 'Risk of bias' tool, found that there was a high and/or unclear risk of bias across a number of domains. Based on the GRADE approach, the overall certainty of evidence for each pooled outcome ranged from low to very low.It is uncertain whether pharmaceutical care improves medication appropriateness (as measured by an implicit tool), mean difference (MD) -4.76, 95% CI -9.20 to -0.33; 5 studies, N = 517; very low-certainty evidence). It is uncertain whether pharmaceutical care reduces the number of potentially inappropriate medications (PIMs), (standardised mean difference (SMD) -0.22, 95% CI -0.38 to -0.05; 7 studies; N = 1832; very low-certainty evidence). It is uncertain whether pharmaceutical care reduces the proportion of patients with one or more PIMs, (risk ratio (RR) 0.79, 95% CI 0.61 to 1.02; 11 studies; N = 3079; very low-certainty evidence). Pharmaceutical care may slightly reduce the number of potential prescribing omissions (PPOs) (SMD -0.81, 95% CI -0.98 to -0.64; 2 studies; N = 569; low-certainty evidence), however it must be noted that this effect estimate is based on only two studies, which had serious limitations in terms of risk bias. Likewise, it is uncertain whether pharmaceutical care reduces the proportion of patients with one or more PPOs (RR 0.40, 95% CI 0.18 to 0.85; 5 studies; N = 1310; very low-certainty evidence). Pharmaceutical care may make little or no difference in hospital admissions (data not pooled; 12 studies; N = 4052; low-certainty evidence). Pharmaceutical care may make little or no difference in quality of life (data not pooled; 12 studies; N = 3211; low-certainty evidence). Medication-related problems were reported in eight studies (N = 10,087) using different terms (e.g. adverse drug reactions, drug-drug interactions). No consistent intervention effect on medication-related problems was noted across studies.
AUTHORS' CONCLUSIONS: It is unclear whether interventions to improve appropriate polypharmacy, such as reviews of patients' prescriptions, resulted in clinically significant improvement; however, they may be slightly beneficial in terms of reducing potential prescribing omissions (PPOs); but this effect estimate is based on only two studies, which had serious limitations in terms of risk bias.
不适当的多重用药是老年人特别关注的问题,且与不良健康后果相关。选择最佳干预措施以改善适当的多重用药是当务之急,因此,对于适当的多重用药(使用多种药物可能为患者带来更好的临床结果)的关注日益增加。这是本Cochrane系统评价的第二次更新。
确定哪些单独或联合的干预措施能有效改善老年人多重用药的合理使用并减少与用药相关的问题。
截至2018年2月7日,我们检索了Cochrane系统评价数据库、MEDLINE、Embase、CINAHL以及两个试验注册库,并通过手工检索参考文献列表以识别其他研究。
我们纳入了随机试验、非随机试验、前后对照研究和中断时间序列研究。符合条件的研究描述了旨在改善65岁及以上老年人合理多重用药的影响处方的干预措施,这些老年人使用了多种药物(四种或更多种药物),且使用了经过验证的工具来评估处方的适宜性。这些工具可分为隐性工具(基于判断/基于专家专业判断)或显性工具(基于标准,包括老年人应避免使用的药物清单)。
两位综述作者独立审查符合条件的研究的摘要,提取数据并评估纳入研究的偏倚风险。我们汇总了研究特异性估计值,并使用随机效应模型得出效应的汇总估计值和95%置信区间(CI)。我们使用GRADE方法评估每个结局的证据总体确定性。
我们识别出32项研究,其中20项来自本次更新。纳入的研究包括18项随机试验、10项整群随机试验(其中一项为阶梯楔形设计)、两项非随机试验和两项前后对照研究。一项干预措施包括计算机化决策支持(CDS);31项为基于复杂、多方面药学服务的方法(即负责提供药物以改善患者结局),其中一项将CDS组件纳入其多方面干预措施中。干预措施在多种环境中提供。干预措施由全科医生、药剂师和老年病医生等医疗专业人员实施,所有研究均在高收入国家进行。使用Cochrane“偏倚风险”工具进行评估发现,在多个领域存在高和/或不明确的偏倚风险。基于GRADE方法,每个汇总结局的证据总体确定性范围从低到极低。尚不确定药学服务是否能改善用药适宜性(通过隐性工具衡量),平均差(MD)为-4.76,95%CI为-9.20至-0.33;5项研究,N = 517;极低确定性证据)。尚不确定药学服务是否能减少潜在不适当用药(PIM)的数量,(标准化平均差(SMD)为-0.22,95%CI为-0.38至-0.05;7项研究;N = 1832;极低确定性证据)。尚不确定药学服务是否能降低有一项或多项PIM的患者比例,(风险比(RR)为0.79,95%CI为0.61至1.02;11项研究;N = 3079;极低确定性证据)。药学服务可能会略微减少潜在处方遗漏(PPO)的数量(SMD为-0.81,95%CI为-0.98至-0.64;2项研究;N = 569;低确定性证据),然而必须指出,这一效应估计仅基于两项研究,这两项研究在风险偏倚方面存在严重局限性。同样,尚不确定药学服务是否能降低有一项或多项PPO的患者比例(RR为0.40,95%CI为0.18至0.85;5项研究;N = 1310;极低确定性证据)。药学服务可能对住院率影响很小或无影响(未汇总数据;12项研究;N = 4052;低确定性证据)。药学服务可能对生活质量影响很小或无影响(未汇总数据;12项研究;N = 3211;低确定性证据)。八项研究(N = 10,087)使用不同术语(如药物不良反应、药物相互作用)报告了与用药相关的问题。各研究中未发现对与用药相关问题的一致干预效果。
尚不清楚改善适当多重用药的干预措施,如审查患者处方,是否能带来临床上显著的改善;然而,它们可能在减少潜在处方遗漏(PPO)方面略有益处;但这一效应估计仅基于两项研究,这两项研究在风险偏倚方面存在严重局限性。