Background: 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. Methods:We conducted a systematic review of observational studies in high-income countries that used patientlevel 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 (NNT H ) calculation on factors when applicable. Results: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, I 2 = 99.9%), depression (RR 1.38, 95% CI 1.27 to 1.51, I 2 = 0%), emergency department visits (RR 1.53, 95% CI 1.46 to 1.61, I 2 = 0%, NNT H 15, 95% CI 12 to 20), unemployment (RR 1.44, 95% CI 1.27 to 1.63, I 2 = 0%), and male gender (RR 1.21, 95% CI 1.14 to 1.28, I 2 = 78.6%) were significantly associated with the prescribing of high-dose opioids in primary care.Conclusions: High doses of opioids are associated with greater risks of harms. Associated factors such as the coprescription 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. Study registration: PROSPERO, CRD42018088057

Background: Cardiovascular disease (CVD) such as ischemic heart disease and stroke is the leading causes of death and disability globally with a growing burden in low and middle-income countries. A credible way of managing the incidence and prevalence of cardiovascular diseases is by reducing risk factors. This understanding has led to the development and recommendation for the clinical use of cardiovascular risk stratification tools. These tools enhance clinical decision-making. However, there is a lag in the implementation of these tools in most countries. This systematic review seeks to synthesise the current knowledge of the factors influencing the implementation of cardiovascular risk scoring in primary care settings. Methods: We searched bibliographic databases and grey literature for studies of any design relating to the topic. Titles, abstracts and full texts were independently assessed for eligibility by two reviewers. This was followed by quality assessment and data extraction. We analysed data using an integrated and best fit framework synthesis approach to identify these factors. Quantitative and qualitative forms of data were combined into a single mixedmethods synthesis. The Consolidated Framework for Implementation Research was used as the guiding tool and template for this analysis. Results: Twenty-five studies (cross-sectional n = 12, qualitative n = 9 and mixed-methods n = 4) were included in this review. Twenty (80%) of these were conducted in high-income countries. Only four studies (16%) included patients as participants. This review reports on a total of eleven cardiovascular risk stratification tools. The factors influencing the implementation of cardiovascular risk scoring are related to clinical setting and healthcare system (resources, priorities, practice culture and organisation), users (attributes and interactions between users) and the specific cardiovascular risk tool (characteristics, perceived role and effectiveness). Conclusions: While these findings bolster the understanding of implementation complexity, there exists limited research in the context of low and middle-income countries. Notwithstanding the need to direct resources in bridging this gap, it is also crucial that these efforts are in concert with providing high-quality evidence on the clinical effectiveness of using cardiovascular risk scoring to improve cardiovascular disease outcomes of mortality and morbidity. Trial registration: PROSPERO registration number: CRD42018092679.

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