Cross Amanda J, Elliott Rohan A, Petrie Kate, Kuruvilla Lisha, George Johnson
Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Australia.
Pharmacy Department, Austin Health, Heidelberg, Australia.
Cochrane Database Syst Rev. 2020 May 8;5(5):CD012419. doi: 10.1002/14651858.CD012419.pub2.
Older people taking multiple medications represent a large and growing proportion of the population. Managing multiple medications can be challenging, and this is especially the case for older people, who have higher rates of comorbidity and physical and cognitive impairment than younger adults. Good medication-taking ability and medication adherence are necessary to ensure safe and effective use of medications.
To evaluate the effectiveness of interventions designed to improve medication-taking ability and/or medication adherence in older community-dwelling adults prescribed multiple long-term medications.
We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL Plus, and International Pharmaceutical Abstracts from inception until June 2019. We also searched grey literature, online trial registries, and reference lists of included studies.
We included randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs. Eligible studies tested interventions aimed at improving medication-taking ability and/or medication adherence among people aged ≥ 65 years (or of mean/median age > 65 years), living in the community or being discharged from hospital back into the community, and taking four or more regular prescription medications (or with group mean/median of more than four medications). Interventions targeting carers of older people who met these criteria were also included.
Two review authors independently reviewed abstracts and full texts of eligible studies, extracted data, and assessed risk of bias of included studies. We conducted meta-analyses when possible and used a random-effects model to yield summary estimates of effect, risk ratios (RRs) for dichotomous outcomes, and mean differences (MDs) or standardised mean differences (SMDs) for continuous outcomes, along with 95% confidence intervals (CIs). Narrative synthesis was performed when meta-analysis was not possible. We assessed overall certainty of evidence for each outcome using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). Primary outcomes were medication-taking ability and medication adherence. Secondary outcomes included health-related quality of life (HRQoL), emergency department (ED)/hospital admissions, and mortality.
We identified 50 studies (14,269 participants) comprising 40 RCTs, six cluster-RCTs, and four quasi-RCTs. All included studies evaluated interventions versus usual care; six studies also reported a comparison between two interventions as part of a three-arm RCT design. Interventions were grouped on the basis of their educational and/or behavioural components: 14 involved educational components only, 7 used behavioural strategies only, and 29 provided mixed educational and behavioural interventions. Overall, our confidence in results regarding the effectiveness of interventions was low to very low due to a high degree of heterogeneity of included studies and high or unclear risk of bias across multiple domains in most studies. Five studies evaluated interventions for improving medication-taking ability, and 48 evaluated interventions for improving medication adherence (three studies evaluated both outcomes). No studies involved educational or behavioural interventions alone for improving medication-taking ability. Low-quality evidence from five studies, each using a different measure of medication-taking ability, meant that we were unable to determine the effects of mixed interventions on medication-taking ability. Low-quality evidence suggests that behavioural only interventions (RR 1.22, 95% CI 1.07 to 1.38; 4 studies) and mixed interventions (RR 1.22, 95% CI 1.08 to 1.37; 12 studies) may increase the proportions of people who are adherent compared with usual care. We could not include in the meta-analysis results from two studies involving mixed interventions: one had a positive effect on adherence, and the other had little or no effect. Very low-quality evidence means that we are uncertain of the effects of educational only interventions (5 studies) on the proportions of people who are adherent. Low-quality evidence suggests that educational only interventions (SMD 0.16, 95% CI -0.12 to 0.43; 5 studies) and mixed interventions (SMD 0.47, 95% CI -0.08 to 1.02; 7 studies) may have little or no impact on medication adherence assessed through continuous measures of adherence. We excluded 10 studies (4 educational only and 6 mixed interventions) from the meta-analysis including four studies with unclear or no available results. Very low-quality evidence means that we are uncertain of the effects of behavioural only interventions (3 studies) on medication adherence when assessed through continuous outcomes. Low-quality evidence suggests that mixed interventions may reduce the number of ED/hospital admissions (RR 0.67, 95% CI 0.50 to 0.90; 11 studies) compared with usual care, although results from six further studies that we were unable to include in meta-analyses indicate that the intervention may have a smaller, or even no, effect on these outcomes. Similarly, low-quality evidence suggests that mixed interventions may lead to little or no change in HRQoL (7 studies), and very low-quality evidence means that we are uncertain of the effects on mortality (RR 0.93, 95% CI 0.67 to 1.30; 7 studies). Moderate-quality evidence shows that educational interventions alone probably have little or no effect on HRQoL (6 studies) or on ED/hospital admissions (4 studies) when compared with usual care. Very low-quality evidence means that we are uncertain of the effects of behavioural interventions on HRQoL (1 study) or on ED/hospital admissions (2 studies). We identified no studies evaluating effects of educational or behavioural interventions alone on mortality. Six studies reported a comparison between two interventions; however due to the limited number of studies assessing the same types of interventions and comparisons, we are unable to draw firm conclusions for any outcomes.
AUTHORS' CONCLUSIONS: Behavioural only or mixed educational and behavioural interventions may improve the proportion of people who satisfactorily adhere to their prescribed medications, but we are uncertain of the effects of educational only interventions. No type of intervention was found to improve adherence when it was measured as a continuous variable, with educational only and mixed interventions having little or no impact and evidence of insufficient quality to determine the effects of behavioural only interventions. We were unable to determine the impact of interventions on medication-taking ability. The quality of evidence for these findings is low due to heterogeneity and methodological limitations of studies included in the review. Further well-designed RCTs are needed to investigate the effects of interventions for improving medication-taking ability and medication adherence in older adults prescribed multiple medications.
服用多种药物的老年人在人口中所占比例很大且呈增长趋势。管理多种药物可能具有挑战性,对于老年人而言尤其如此,因为他们的合并症发生率以及身体和认知障碍发生率均高于年轻人。良好的服药能力和药物依从性对于确保安全有效地用药至关重要。
评估旨在提高社区居住的、服用多种长期药物的老年成年人服药能力和/或药物依从性的干预措施的有效性。
我们检索了MEDLINE、Embase、Cochrane对照试验中心注册库(CENTRAL)、PsycINFO、CINAHL Plus以及国际药学文摘数据库,检索时间从各数据库建库至2019年6月。我们还检索了灰色文献、在线试验注册库以及纳入研究的参考文献列表。
我们纳入了随机对照试验(RCT)、半随机对照试验和整群随机对照试验。符合条件的研究测试了旨在提高年龄≥65岁(或平均/中位年龄>65岁)、居住在社区或从医院出院后回到社区且正在服用四种或更多常规处方药(或组平均/中位数超过四种药物)的人群的服药能力和/或药物依从性的干预措施。针对符合这些标准的老年人的护理人员的干预措施也被纳入。
两位综述作者独立审查了符合条件的研究的摘要和全文,提取数据,并评估纳入研究的偏倚风险。我们尽可能进行荟萃分析,并使用随机效应模型得出效应的汇总估计值、二分结局的风险比(RR)以及连续结局的平均差(MD)或标准化平均差(SMD),以及95%置信区间(CI)。当无法进行荟萃分析时,进行叙述性综合分析。我们使用推荐分级、评估、制定与评价(GRADE)对每个结局的证据总体确定性进行评估。主要结局是服药能力和药物依从性。次要结局包括健康相关生活质量(HRQoL)、急诊科(ED)就诊/住院以及死亡率。
我们识别出50项研究(14269名参与者),包括40项RCT、6项整群随机对照试验和4项半随机对照试验。所有纳入研究均评估了干预措施与常规护理的对比;6项研究还报告了作为三臂RCT设计一部分的两种干预措施之间的比较。干预措施根据其教育和/或行为成分进行分组:14项仅涉及教育成分,7项仅使用行为策略,29项提供了教育和行为相结合的干预措施。总体而言,由于纳入研究的高度异质性以及大多数研究在多个领域存在高或不明确的偏倚风险,我们对干预措施有效性结果的信心较低至非常低。5项研究评估了改善服药能力的干预措施,48项评估了改善药物依从性的干预措施(3项研究评估了这两个结局)。没有研究仅涉及教育或行为干预来改善服药能力。来自5项研究的低质量证据,每项研究使用不同的服药能力衡量方法,这意味着我们无法确定综合干预措施对服药能力的影响。低质量证据表明,仅行为干预(RR 1.22,95%CI 1.07至1.38;4项研究)和综合干预(RR 1.22,95%CI 1.08至1.37;12项研究)与常规护理相比,可能会增加依从人群的比例。我们无法将两项涉及综合干预的研究结果纳入荟萃分析:一项对依从性有积极影响,另一项几乎没有影响或没有影响。极低质量证据意味着我们不确定仅教育干预(5项研究)对依从人群比例产生的影响。低质量证据表明,仅教育干预(SMD 0.16,95%CI -0.12至0.43;5项研究)和综合干预(SMD 0.47,95%CI -0.08至1.02;7项研究)通过连续的依从性测量评估时,可能对药物依从性几乎没有影响。我们从荟萃分析中排除了10项研究(4项仅教育干预和6项综合干预),包括4项结果不明确或无可用结果的研究。极低质量证据意味着当通过连续结局评估时,我们不确定仅行为干预(3项研究)对药物依从性的影响。低质量证据表明,与常规护理相比,综合干预可能会减少ED/住院次数(RR 0.67,95%CI 0.50至0.90;11项研究),尽管我们无法纳入荟萃分析的另外6项研究结果表明该干预措施对这些结局的影响可能较小,甚至没有影响。同样,低质量证据表明,综合干预可能对HRQoL几乎没有影响或没有变化(7项研究),极低质量证据意味着我们不确定对死亡率的影响(RR 0.93,95%CI 0.67至1.30;7项研究)。中等质量证据表明,与常规护理相比,仅教育干预可能对HRQoL(6项研究)或ED/住院次数(4项研究)几乎没有影响。极低质量证据意味着我们不确定行为干预对HRQoL(1项研究)或ED/住院次数(2项研究)的影响。我们未识别出评估仅教育或行为干预对死亡率影响的研究。6项研究报告了两种干预措施之间的比较;然而,由于评估相同类型干预措施和比较的研究数量有限,我们无法对任何结局得出确切结论。
仅行为干预或教育与行为相结合的干预措施可能会提高令人满意地坚持服用处方药的人群比例,但我们不确定仅教育干预的效果。当将依从性作为连续变量测量时,未发现任何类型的干预措施能改善依从性,仅教育干预和综合干预几乎没有影响,且证据质量不足以确定仅行为干预的效果。我们无法确定干预措施对服药能力的影响。由于综述中纳入研究的异质性和方法学局限性,这些发现的证据质量较低。需要进一步设计良好的RCT来研究干预措施对服用多种药物的老年人改善服药能力和药物依从性的影响。