The occurrence of drug-drug-interactions (DDI) from multiple drug dispensations is a serious problem, both for individuals and health-care systems, since patients with complications due to DDI are likely to reenter the system at a costlier level. We present a large-scale longitudinal study (18 months) of the DDI phenomenon at the primary- and secondary-care level using electronic health records (EHR) from the city of Blumenau in Southern Brazil (pop. ≈340,000). We found that 181 distinct drug pairs known to interact were dispensed concomitantly to 12% of the patients in the city's public health-care system. Further, 4% of the patients were dispensed drug pairs that are likely to result in major adverse drug reactions (ADR)-with costs estimated to be much larger than previously reported in smaller studies. The large-scale analysis reveals that women have a 60% increased risk of DDI as compared to men; the increase becomes 90% when considering only DDI known to lead to major ADR. Furthermore, DDI risk increases substantially with age; patients aged 70-79 years have a 34% risk of DDI when they are dispensed two or more drugs concomitantly. Interestingly, a statistical null model demonstrates that age- and female-specific risks from increased polypharmacy fail by far to explain the observed DDI risks in those populations, suggesting unknown social or biological causes. We also provide a network visualization of drugs and demographic factors that characterize the DDI phenomenon and demonstrate that accurate DDI prediction can be included in health care and public-health management, to reduce DDI-related ADR and costs.

中文翻译：

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全市范围内的电子健康记录揭示了已知药物-药物相互作用管理中的性别和年龄偏见。

对于个人和卫生保健系统而言，由于多种药物分配产生的药物相互作用（DDI）都是一个严重的问题，因为患有DDI并发症的患者很可能会以更高的价格重新进入系统。我们使用来自巴西南部布鲁曼瑙市的电子健康记录（EHR），对初级和二级医疗水平的DDI现象进行了大规模的纵向研究（18个月）（人口约340,000）。我们发现，该市的公共卫生保健系统中有181种不同的已知药物对同时被分配给了12％的患者。此外，有4％的患者分配了可能导致重大药物不良反应（ADR）的配药对-费用估计比以前在较小的研究中报道的要大得多。大规模分析表明，与男性相比，女性罹患DDI的风险增加了60％；如果仅考虑已知会导致主要ADR的DDI，则增加幅度为90％。此外，DDI风险会随着年龄的增长而大大增加；年龄在70-79岁之间的患者在同时分配两种或两种以上药物时有34％的DDI风险。有趣的是，一个统计无效模型表明，由于混合药店的增加，特定于年龄和女性的风险远远不能解释在这些人群中观察到的DDI风险，暗示了未知的社会或生物学原因。我们还提供了代表DDI现象特征的药物和人口统计因素的网络可视化，并证明了可以在医疗保健和公共卫生管理中包括准确的DDI预测，以减少与DDI相关的ADR和成本。