The Effect of Human Supervision on an Electronic Implementation of the Canadian Triage Acuity Scale (CTAS).

BACKGROUND: Most electronic emergency department (ED) triage systems allow nurses to modify computer-generated triage scores. It is currently unclear how this affects triage validity. OBJECTIVE: Are nurse-generated triage scores more strongly associated with rates of admission, intensive care unit (ICU) consultation, and mortality than computer-generated scores? METHODS: Retrospective observational cohort study of all adult visits to a tertiary ED. An electronic implementation of the Canadian Triage Acuity Scale (CTAS) generated a CTAS score for each visit. In some cases, the triage nurse overwrote the computer-generated CTAS score with a score they felt was more appropriate. Among visits with nurse-modified triage scores, we compared the rate of acuity-related outcomes (mortality, ICU consultation, hospital admission) in each CTAS level as categorized by nurse-generated vs. computer-generated scores. RESULTS: In a cohort of 229,744 patients, 19,566 (8.51%) had nurse-modified triage scores. Most modifications consisted of assigning a higher acuity triage score than recommended by the computer. Visits with triage scores 1-2 according to the nurse-generated scores had the same or higher rates of the acuity outcomes than visits that were CTAS 1-2 according to the computer-generated CTAS scores. Conversely, visits with triage scores 4-5 according to the nurse-generated scores had lower rates of the outcomes than visits that were CTAS 4-5 according to the computer-generated CTAS scores. CONCLUSIONS: Nursing supervision of the computer-automated CTAS triage system was associated with fewer hospital admissions, ICU consultations, and deaths in the triage score 4-5 categories, suggesting a safer triage process than the automated CTAS algorithm alone.

Impact of Pain Assessment on Canadian Triage and Acuity Scale Prediction of Patient Outcomes.

STUDY OBJECTIVE: How does the removal of patient-reported pain from the Canadian Triage Acuity Scale (CTAS) affect the scale's ability to predict admission, ICU consultation, and mortality? METHODS: Retrospective observational cohort study of all adult visits to a tertiary emergency department. The standard CTAS algorithm combined patient-reported pain levels with other data to generate a triage score for each visit. We calculated a "pain-free" CTAS for each visit in the cohort, assuming that the patient had not reported any pain. We fit logistic regression models for each outcome (admission, ICU consultation, and mortality) using either the standard or the pain-free CTAS as the predictor. We compared the area under the receiver operator characteristic curves of the standard versus pain-free CTAS models for each outcome. RESULTS: We analyzed a sample of 229,744 patients. The average reported pain level was 5.6/10 (SD, 3.0) among the 60.1% of the cohort who reported pain. Higher pain was slightly negatively correlated with hospital admission, ICU consultation, and 72-hour mortality (r = -0.008, -0.009, and -0.006, respectively). The area under the curve of the pain-free CTAS was higher than that of the standard scores for hospital admission (0.691 versus 0.641), ICU consultation (0.829 versus 0.773), and mortality (0.863 versus 0.810). Differences were statistically but not clinically significant. CONCLUSION: The removal of the pain scale from CTAS did not reduce its ability to predict hospital admission, ICU consultation, or the 72-hour mortality.

Integrated genome-wide methylation and expression analyses reveal functional predictors of response to antidepressants.

Major depressive disorder (MDD) is primarily treated with antidepressants, yet many patients fail to respond adequately, and identifying antidepressant response biomarkers is thus of clinical significance. Some hypothesis-driven investigations of epigenetic markers for treatment response have been previously made, but genome-wide approaches remain unexplored. Healthy participants (n = 112) and MDD patients (n = 211) between 18-60 years old were recruited for an 8-week trial of escitalopram treatment. Responders and non-responders were identified using differential Montgomery-Åsberg Depression Rating Scale scores before and after treatment. Genome-wide DNA methylation and gene expression analyses were assessed using the Infinium MethylationEPIC Beadchip and HumanHT-12 v4 Expression Beadchip, respectively, on pre-treatment peripheral blood DNA and RNA samples. Differentially methylated positions (DMPs) located in regions of differentially expressed genes between responders (n = 82) and non-responders (n = 95) were identified, and technically validated using a targeted sequencing approach. Three DMPs located in the genes CHN2 (cg23687322, p = 0.00043 and cg06926818, p = 0.0014) and JAK2 (cg08339825, p = 0.00021) were the most significantly associated with mRNA expression changes and subsequently validated. Replication was then conducted with non-responders (n = 76) and responders (n = 71) in an external cohort that underwent a similar antidepressant trial. One CHN2 site (cg06926818; p = 0.03) was successfully replicated. Our findings indicate that differential methylation at CpG sites upstream of the CHN2 and JAK2 TSS regions are possible peripheral predictors of antidepressant treatment response. Future studies can provide further insight on robustness of our candidate biomarkers, and greater characterization of functional components.

Using Epigenetic Tools to Investigate Antidepressant Response.

Major depressive disorder is a chronic and debilitating illness. It is most commonly treated with antidepressant drugs, however, as the majority of patients do not respond on their first trial or following several adequate trials, there is great interest in identifying biological factors that may help select the most appropriate treatment for each patient and in understanding biological processes that mediate treatment response. Epigenetic factors, such as non-coding RNAs (ncRNAs), hold potential as biomarkers of antidepressant response. In this chapter, we review key methodological considerations when investigating ncRNA biomarkers, including biological samples and technologies which have been used in these studies. Secondly, we summarize findings from studies investigating ncRNAs in antidepressant treatment response. Finally, we discuss some of the future directions which will be necessary for the development of clinically relevant epigenetic tools.

Transcriptomic and epigenomic biomarkers of antidepressant response.

BACKGROUND: Antidepressant treatment is associated with a high rate of poor response, and thus, biomarker development is warranted. METHODS: We aimed to synthesize studies investigating gene expression, small RNAs, and epigenomic biomarkers of antidepressant response. We conducted a narrative review of the literature. RESULTS: Firstly, we detailed the challenges involved, in terms of biological tissues, relevant study time frames, and mandatory statistical tools. Secondly we synthesized results obtained in gene expression studies, focusing mainly on genome-wide studies, particularly small non-coding RNA, including micro-RNA and other small RNA species. In addition, we reviewed the potential biomarkers of antidepressant response arising from studies investigating DNA methylation variation and histone modifications. LIMITATIONS: We did not conduct a meta-analysis due to the heterogeneity of the study. CONCLUSION: Although promising, the field of gene expression and epigenomic biomarkers of antidepressant response is still in its infancy, and needs further development to define useful biomarkers in clinical practice.