Background: The clinical decision support system (CDSS) has become an indispensable tool for reducing medication errors and adverse drug events. However, numerous studies have reported that CDSS alerts are often overridden. The increase in override rates has raised questions about the appropriateness of CDSS application along with concerns about patient safety and quality of care. Objective: The aim of this study was to conduct a systematic review to examine the override rate, the reasons for the alert override at the time of prescribing, and evaluate the appropriateness of overrides. Methods: We searched electronic databases, including Google Scholar, PubMed, Embase, Scopus, and Web of Science, without language restrictions between January 1, 2000 and March 31, 2019. Two authors independently extracted data and crosschecked the extraction to avoid errors. The quality of the included studies was examined following Cochrane guidelines. Results: We included 23 articles in our systematic review. The range of average override alerts was 46.2%-96.2%. An average of 29.4%-100% of the overrides alerts were classified as appropriate, and the rate of appropriateness varied according to the alert type (drug-allergy interaction 63.4%-100%, drug-drug interaction 0%-95%, dose 43.9%-88.8%, geriatric 14.3%-57%, renal 27%-87.5%). The interrater reliability for the assessment of override alerts appropriateness was excellent (kappa=0.79-0.97). The most common reasons given for the override were “will monitor” and “patients have tolerated before.” Conclusions: The findings of our study show that alert override rates are high, and certain categories of overrides such as drug-drug interaction, renal, and geriatric were classified as inappropriate. Nevertheless, large proportions of drug duplication, drug-allergy, and formulary alerts were appropriate, suggesting that these groups of alerts can be primary targets to revise and update the system for reducing alert fatigue. Future efforts should also focus on optimizing alert types, providing clear information, and explaining the rationale of the alert so that essential alerts are not inappropriately overridden.

Background and Aims: Statins are the first-line medication to treating hypercholesterolemia. Several studies have investigated the impact of statins on the risk of hepatocellular carcinoma (HCC). However, the extent to which statins may prevent HCC remains uncertain. Therefore, we performed a meta-analysis of relevant studies to quantify the magnitude of the association between statins use and the risk of HCC. Methods: A systematic literature search of PubMed, EMBASE, Google Scholar, Web of Science, and Scopus was performed for studies published between January 1, 1990, and September 1, 2019, with no restriction of language. Two reviewers independently evaluated the literature and included observational and experimental studies that reported the association between statin use and HCC risk. The random-effect model was used to calculate the overall risk ratio (RR) with a 95% confidence interval (CI), and the heterogeneity among the studies was assessed using the Q statistic and I² statistic. The Newcastle Ottawa Scale (NOS) was also used to evaluate the quality of the included studies. Results: A total of 24 studies with 59,073 HCC patients was identified. Statin use was associated with a reduced risk of HCC development (RR: 0.54, 95% CI: 0.47–0.61, I² = 84.39%) compared with nonusers. Moreover, the rate of HCC reduction was also significant among patients with diabetes (RR: 0.44, 95% CI: 0.28–0.70), liver cirrhosis (RR: 0.36, 95% CI: 0.30–0.42), and antiviral therapy (RR: 0.21, 95% CI: 0.08–0.59) compared with nonusers. Conclusion: This study serves as additional evidence supporting the beneficial inhibitory effect of statins on HCC incidence. The subgroup analyses of this study also highlight that statins are significantly associated with a reduced risk of HCC and may help to direct future prevention efforts. Additional large clinical studies are needed to determine whether statins are associated with a lower risk of HCC.

Chronic infection with hepatitis B virus (HBV) often causes chronic inflammation of the liver with an increased incidence of hepatocellular carcinoma (HCC). HBV-infected individuals may also have an increased incidence of nonliver cancers. Taking statin or metformin may decrease inflammation and infiltration, which may, as a result, reduce the risk of liver cancer or other major cancers in patients with HBV infection. The purpose of this study was to evaluate the hypothesis that statin and metformin could reduce the incidence of liver cancer (HCC) or nonliver cancers in patients with HBV. Using the Taiwan Longitudinal Health Insurance Database 2000 to 2008, this cohort study comprised patients with a recorded diagnosis of HBV (N = 71,847) between January 1, 2000 and December 31, 2008. Each patient was followed-up until the end of 2008. The occurrence of HCC or a nonliver cancer was evaluated in patients who either were or were not taking statin or metformin. Cox proportional hazard regressions were used to evaluate the cancer incidence after adjusting for known confounding factors. In total, 71,824 HBV-infected patients comprised the study cohort. Our study showed that either metformin or statin use was associated with a reduction in the incidence of cancer. This was most prominent in patients taking both statin and metformin. The adjusted hazard ratios (HRs) for patients using only statin were 0.52 (95% confidence interval [CI], 0.48–0.57) for all cancers, 0.28 (95% CI, 0.23–0.35) for liver cancer, and 0.63 (95% CI, 0.57–0.70) for nonliver cancers. Patients taking only metformin had risk-adjusted HRs of 0.82 (95% CI, 0.75–0.90) for all cancers, 0.97 (95% CI, 0.84–1.14) for liver cancer, and 0.75 (95% CI, 0.67–0.84) for nonliver cancers. A dose-dependent effect of statin use for chemoprevention was observed for all cancers, including both liver cancer and nonliver cancers. A dose-dependent effect of metformin was also seen in liver cancer and nonliver cancers without stratification into different cumulative daily doses of statin use. This population-based cohort study investigated the protective effect of statin and metformin against cancer events in patients with HBV infection. Our study demonstrated that either statin or metformin served as independent chemopreventive agents with a dose–response effect in reducing the incidence of cancer with a dose–response effect of the agents and an additive or synergistic effect of combining statin and metformin use in reducing the incidence of many cancers.