Based on inpatient EHR, MDPs were applied to describe and analyze the dynamic process of different combinations of TCM treatments and/or integrated treatments of TCM and Western medicine for patients with AIS, and to determine the optimal treatment combination for each State by comparing the rewards gained from the corresponding actions. To the best of our knowledge, no similar topic has been previously addressed in the field of integrative medicine (IM) or in complementary and alternative medicine (CAM).
No medication has yet been confirmed to have neuroprotective effects in the management of patients with AIS [28
]. Although antiplatelet agents can reduce the risk of mortality and morbidity when aspirin is administered within 48 hours after the onset of stroke, it cannot be used in up to 28% patients with aspirin "resistance" [29
]. The management of patients with AIS with heparin carries an increased risk of bleeding complications [30
]. The use of intravenous recombinant tissue plasminogen activators (rt-PA) in cerebral infarctions is associated with improved outcomes, but cannot be used as a routine therapy outside special units [31
Several commonly used and government-approved traditional Chinese patent medicines (TCPMs), such as, Ginkgo biloba
], milk vetch [33
], Mailuoning [35
], Qingkailing [36
], and Danshen [37
] agents, have shown promising effects for ischemic stroke. However, no definite conclusions can be drawn from studies of these agents due to a general lack of reporting on methodology [30
]. Properly designed clinical research to study the role of traditional medicine in ischemic stroke is warranted, but a number of issues must be addressed in the design of such studies first [41
]. One of these issues is complex interventions involving varying dosages and interactions. Randomized controlled trials (RCTs) are a possible approach to evaluating complex interventions as a whole compared with an appropriate alternative [42
], but cannot separate the benefits of different combinations of components. The multi-component structure of treatments is closer to real world practice, especially in therapy for stroke with complex dynamics from onset through progression [43
]. Moreover, the model of applying a treatment and conducting it without any change through the whole course of acute stroke is inconsistent with the basic theory of TCM whereby treatment is altered according to syndrome differentiation [15
The results of this study indicate that the new method of MDPs may prove useful for comparative effectiveness research (CER). MDPs can be applied to dynamically compare the effectiveness of various combinations of complex treatments, and may be able to overcome the uncertainties related to individual patients' responses to certain combination of treatments and the uncertainties concerning dynamic changes in treatment for certain patients over the course of disease [21
Past research implies that herbal medicine may possess neuroprotective properties [46
], protect against ischemic reperfusion injury [48
], reduce edema in the brain [48
], improve cerebral microcirculation [33
], and inhibit apoptosis [50
]. Such properties may partly explain the effectiveness of the combinations of treatments identified in this research.
This study has several limitations. First, all of the data were taken from EHR, and missing data are inevitable. The amount of missing data was less than 1.12% in most categories, although 18.39% of missing data was detected in i6. As i6 is a key variable in describing the rewards of actions, the results should be interpreted cautiously because of the possible bias caused by the replacement of missing data. In addition, due to too much variety, different components of herbal medicine were classified as one action. As a result, the effectiveness of different prescriptions of herbal medicine is not comparable. Another limitation is that each patient's record was divided into two stages according to three time points, with each episode being regarded as an independent sample when modeled by MDPs. This is consistent with the Markov property of non-after effect according to the basic theory of MDPs, but it may, to a certain extent, ignore potential correlations between episodes obtained from the same patient at different stages. Finally, although the key characteristics representing the patient states were based on the results of an expert panel meeting, the states of patients with acute ischemic stroke are variable, and it is likely that some characteristics that might be important for certain patients were missed.