Drug-drug interactions with warfarin: A systematic review and meta-analysis.

AIMS: The objective of this paper is to systematically review the literature on drug-drug interactions with warfarin, with a focus on patient-important clinical outcomes. METHODS: MEDLINE, EMBASE and the International Pharmaceutical Abstract (IPA) databases were searched from January 2004 to August 2019. We included studies describing drug-drug interactions between warfarin and other drugs. Screening and data extraction were conducted independently and in duplicate. We synthesized pooled odds ratios (OR) with 95% confidence intervals (CIs), comparing warfarin plus another medication to warfarin alone. We assessed the risk of bias at the study level and evaluated the overall certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Of 42 013 citations identified, a total of 72 studies reporting on 3 735 775 patients were considered eligible, including 11 randomized clinical trials and 61 observational studies. Increased risk of clinically relevant bleeding when added to warfarin therapy was observed for antiplatelet (AP) regimens (OR = 1.74; 95% CI 1.56-1.94), many antimicrobials (OR = 1.63; 95% CI 1.45-1.83), NSAIDs including COX-2 NSAIDs (OR = 1.83; 95% CI 1.29-2.59), SSRIs (OR = 1.62; 95% CI 1.42-1.85), mirtazapine (OR = 1.75; 95% CI 1.30-2.36), loop diuretics (OR = 1.92; 95% CI 1.29-2.86) among others. We found a protective effect of proton pump inhibitors (PPIs) against warfarin-related gastrointestinal (GI) bleeding (OR = 0.69; 95% CI 0.64-0.73). No significant effect on thromboembolic events or mortality of any drug group used with warfarin was found, including single or dual AP regimens. CONCLUSIONS: This review found low to moderate certainty evidence supporting the interaction between warfarin and a small group of medications, which result in increased bleeding risk. PPIs are associated with reduced hospitalization for upper GI bleeding for patients taking warfarin. Further studies are required to better understand drug-drug interactions leading to thromboembolic outcomes or death.

The development and validation of an instrument to measure the quality of health research reports in the lay media.

BACKGROUND: The media serves as an important link between medical research, as reported in scholarly sources, and the public and has the potential to act as a powerful tool to improve public health. However, concerns about the reliability of health research reports have been raised. Tools to monitor the quality of health research reporting in the media are needed to identify areas of weakness in health research reporting and to subsequently work towards the efficient use of the lay media as a public health tool through which the public's health behaviors can be improved. METHODS: We developed the Quality Index for health-related Media Reports (QIMR) as a tool to monitor the quality of health research reports in the lay media. The tool was developed according to themes generated from interviews with health journalists and researchers. Item and domain characteristics and scale reliability were assessed. The scale was correlated with a global quality assessment score and media report word count to provide evidence towards its construct validity. RESULTS: The items and domains of the QIMR demonstrated acceptable validity and reliability. Items from the 'validity' domain were negatively skewed, suggesting possible floor effect. These items were not eliminated due to acceptable content and face validity. QIMR total scores produced a strong correlation with raters' global assessment and a moderate correlation with media report word count, providing evidence towards the construct validity of the instrument. CONCLUSIONS: The results of this investigation indicate that QIMR can adequately measure the quality of health research reports, with acceptable reliability and validity.