The risks of harms from opioids increase substantially at high doses, and high-dose prescribing has increased in primary care. However, little is known about what leads to high-dose prescribing, and studies exploring this have not been synthesized. We, therefore, systematically synthesized factors associated with the prescribing of high-dose opioids in primary care. We conducted a systematic review of observational studies in high-income countries that used patient-level primary care data and explored any factor(s) in people for whom opioids were prescribed, stratified by oral morphine equivalents (OME). We defined high doses as ≥ 90 OME mg/day. We searched MEDLINE, Embase, Web of Science, reference lists, forward citations, and conference proceedings from database inception to 5 April 2019. Two investigators independently screened studies, extracted data, and appraised the quality of included studies using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. We pooled data on factors using random effects meta-analyses and reported relative risks (RR) or mean differences with 95% confidence intervals (CI) where appropriate. We also performed a number needed to harm (NNTH) calculation on factors when applicable. We included six studies with a total of 4,248,119 participants taking opioids, of whom 3.64% (n = 154,749) were taking high doses. The majority of included studies (n = 4) were conducted in the USA, one in Australia and one in the UK. The largest study (n = 4,046,275) was from the USA. Included studies were graded as having fair to good quality evidence. The co-prescription of benzodiazepines (RR 3.27, 95% CI 1.32 to 8.13, I2 = 99.9%), depression (RR 1.38, 95% CI 1.27 to 1.51, I2 = 0%), emergency department visits (RR 1.53, 95% CI 1.46 to 1.61, I2 = 0%, NNTH 15, 95% CI 12 to 20), unemployment (RR 1.44, 95% CI 1.27 to 1.63, I2 = 0%), and male gender (RR 1.21, 95% CI 1.14 to 1.28, I2 = 78.6%) were significantly associated with the prescribing of high-dose opioids in primary care. High doses of opioids are associated with greater risks of harms. Associated factors such as the co-prescription of benzodiazepines and depression identify priority areas that should be considered when selecting, identifying, and managing people taking high-dose opioids in primary care. Coordinated strategies and services that promote the safe prescribing of opioids are needed. PROSPERO, CRD42018088057

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与初级保健中大剂量阿片类药物处方相关的因素：系统评价和荟萃分析。

大剂量使用阿片类药物造成伤害的风险大大增加，初级保健中使用大剂量处方的情况也有所增加。但是，对于导致大剂量开药的原因知之甚少，并且尚未对此进行研究。因此，我们系统地综合了与初级保健中大剂量阿片类药物处方相关的因素。我们对高收入国家的观察性研究进行了系统的回顾，这些研究使用了患者一级的初级保健数据，并探讨了以口服吗啡等效物（OME）分层的处方阿片类药物的人群中的任何因素。我们将高剂量定义为≥90 OME mg /天。我们搜索了从数据库开始到2019年4月5日的MEDLINE，Embase，Web of Science，参考文献列表，正向引文和会议记录。两名研究人员独立筛选了研究，提取数据，并使用用于观察性队列和跨部门研究的质量评估工具评估纳入研究的质量。我们使用随机效应荟萃分析汇总了有关因素的数据，并在适当的情况下报告了相对风险（RR）或均值差异为95％置信区间（CI）。在适用的情况下，我们还对因子进行了一些损害（NNTH）计算。我们纳入了六项研究，共有4,248,119名参与者服用了阿片类药物，其中3.64％（n = 154,749）正在服用大剂量药物。纳入研究的大多数（n = 4）在美国进行，一项在澳大利亚，一项在英国。最大的研究（n = 4,046,275）来自美国。纳入的研究被评为具有公平至良好质量的证据。苯二氮卓类药物的共同处方（RR 3.27，95％CI 1.32至8.13，I2 = 99.9％），抑郁症（RR 1.38，95％CI 1.27至1.51，I2 = 0％），急诊就诊（RR 1.53，95％CI 1.46至1.61，I2 = 0％，NNTH 15，95％CI 12至20），失业（ RR 1.44、95％CI 1.27至1.63，I2 = 0％和男性（RR 1.21、95％CI 1.14至1.28，I2 = 78.6％）与高剂量阿片类药物在基层医疗中的处方相关。高剂量的阿片类药物会带来更大的伤害风险。诸如苯二氮卓类药物和抑郁症的共同处方等相关因素确定了在选择，识别和管理在初级保健中服用大剂量阿片类药物的人时应考虑的优先领域。需要采取协调一致的战略和服务来促进阿片类药物的安全处方。PROSPERO，CRD42018088057 I2 = 0％，NNTH 15，95％CI 12至20），失业（RR 1.44，95％CI 1.27至1.63，I2 = 0％），男性（RR 1.21，95％CI 1.14至1.28，I2 = 78.6％）与在初级保健中开具大剂量阿片类药物的处方密切相关。高剂量的阿片类药物会带来更大的伤害风险。诸如苯二氮卓类药物和抑郁症的共同处方等相关因素确定了在选择，识别和管理在初级保健中服用大剂量阿片类药物的人时应考虑的优先领域。需要采取协调一致的战略和服务来促进阿片类药物的安全处方。PROSPERO，CRD42018088057 I2 = 0％，NNTH 15，95％CI 12至20），失业（RR 1.44，95％CI 1.27至1.63，I2 = 0％），男性（RR 1.21，95％CI 1.14至1.28，I2 = 78.6％）与在初级保健中开具大剂量阿片类药物的处方密切相关。高剂量的阿片类药物会带来更大的伤害风险。诸如苯二氮卓类药物和抑郁症的共同处方等相关因素确定了在选择，识别和管理在初级保健中服用大剂量阿片类药物的人时应考虑的优先领域。需要采取协调一致的战略和服务来促进阿片类药物的安全处方。PROSPERO，CRD42018088057 6％）与初级保健中大剂量阿片类药物的处方相关。高剂量的阿片类药物会带来更大的伤害风险。诸如苯二氮卓类药物和抑郁症的共同处方等相关因素确定了在选择，识别和管理在初级保健中服用大剂量阿片类药物的人时应考虑的优先领域。需要采取协调一致的战略和服务来促进阿片类药物的安全处方。PROSPERO，CRD42018088057 6％）与初级保健中大剂量阿片类药物的处方相关。高剂量的阿片类药物会带来更大的伤害风险。诸如苯二氮卓类药物和抑郁症的共同处方等相关因素确定了在选择，识别和管理在初级保健中服用大剂量阿片类药物的人时应考虑的优先领域。需要采取协调一致的战略和服务来促进阿片类药物的安全处方。PROSPERO，CRD42018088057 需要采取协调一致的战略和服务来促进阿片类药物的安全处方。PROSPERO，CRD42018088057 需要采取协调一致的战略和服务来促进阿片类药物的安全处方。PROSPERO，CRD42018088057