Article search results
A total of 69 articles were identified through the search strategy. After duplication was removed, 49 articles have remained for screening. From these, 30 articles were excluded by their titles and abstracts. The remaining 19 articles were then evaluated as per predetermined eligibility criteria for inclusion. Five articles were also excluded with justification (Additional file 2: Table 2). Finally, a total of 14 full-text articles that passed the eligibility criteria and quality assessment were included for final review and analysis (Fig. 1).
General characteristics of the included studies
A total of 14 studies were included for systematic review and meta-analysis and important information that were related to study characteristics were presented in Table 2. All studies employed were observational cross-sectional study designs i.e. six retrospectives cross-sectional study (CS); three prospective CS and five CS design. The year of publication of included studies ranges from 2013 to 2019. The study included a wide range of population characteristics (pediatric, adult, and geriatric patients). Regarding geographic distribution, 14 studies were obtained from three regions and one city administration (Addis Ababa). The studies included all types of disease which had been treated in a medical ward and outpatient setting.
Nine articles analyzed patients with all type of pathologies without focusing on any specific disease, two articles analyzed patients with the cardiac disorder, one article studied HIV patients and one article analyzed patients with psychiatric disorders.
Nine articles studied DDIs in inpatient ward (seven articles in a medical ward; one article in a pediatric ward; one article in all wards); four articles studied DDIs in the outpatient setting (ART Clinic, Cardiac Clinic, Psychiatric unit, and Outpatient pharmacy) and one article studied at inpatients and outpatient setting.
Among the fourteen studies analyzed, six different databases were used to detect potential interactions. About half of the studies used Micromedex® 2.0 database systems (seven articles; 50.0 %), two articles (14.2%) used Medscape online, two articles (14.2%) used Micromedex® 3.0 database systems. The other three articles used Medscape online and drug.com, Drug.com and Micromedex online (Table 2)
Quality of included studies
The quality of the included studies ranges from moderate to high quality (Additional file 3: Table 3).
Study outcome measures
Prevalence of potential DDIs
The prevalence and number of potential DDIs for each study are presented in Table 3. From 14 studies, the pooled prevalence of patients with potential DDIs in Ethiopian Hospitals was found to be 72.2% with 95% CI between 59.1 and 85.3). Fig 2 showed heterogeneity across 14 studies were high (I2 = 99.78%, p < 0.001). Based on the severity of DDIs, the pooled prevalence of potential DDIs was 25.1%, 52.8%, 16.9%, and 1.27% for major, moderate, minor potential DDIs and contraindications respectively. Fig 3, 4, and 5 showed heterogeneity across 14 studies was high.
Based on the mechanisms of DDIs involved, seven studies documented well but the remaining seven studies didn’t document well the mechanisms of DDIs (table 4).
Factors associated with potential DDIs
The factors associated with potential DDIs were related to patient characteristics (Table 5).
Common interacting drug-combinations
The most common contraindications, major, and moderate DDIs are presented in Table 6.
Test of heterogeneity, subgroup analysis, and publication bias
Test of heterogeneity
In this review and meta-analysis, there is clinical and statistical heterogeneity. The tests of heterogeneity showed significant heterogeneity (I2=99.78%, p < 0.001). To differentiate heterogeneity, sensitivity analysis, subgroup analysis, and Meta-regression was done.
There was no significant change in the degree of heterogeneity even if an attempt was done to exclude the expected outliers as well as one or more of the studies from the analysis. Therefore, fourteen studies were included for the meta-analysis.
Subgroup analysis also conducted based on Region and Study setting. Subgroup analysis based on a region revealed that the highest prevalence of potential DDIs was observed at Oromia Region, 94.9% (95% CI: 90.3 to 99.5) followed by Tigray Region with a prevalence of 68.6% (95% CI: 42.6 to 94.5) (Fig 6).
Subgroup analysis based on study setting revealed that the highest prevalence of potential DDIs was observed at outpatient: 80.0% (95% CI: 58.9 to 101.1 followed by inpatient: 73.2% (95% CI: 60.8 to 85.7 and inpatient and outpatient setting: 32.6% (95% CI: 30.6 to 34.6).
Univariate meta-regression for prevalence of potential DDIs revealed that sampling distribution is a source of heterogeneity (regression coefficient = 7.36; p-value = 0.0067) (Fig 7)
Funnel plots of standard error with logit effect size i.e. event rate supplemented by statistical tests confirmed that there is no evidence of publication bias on studies reporting the prevalence of potential DDIs and associated factors in Ethiopian Hospitals because there is no higher concentration of studies on one side of the mean than the other at the bottom of the plot (fig 8)