SplintER Series: A Case of Arm Pain
An 80-year-old male presents with severe right arm pain after he tripped and fell down 2 steps. Examination shows deformity and swelling to his right upper arm. You obtain AP and lateral humerus x-rays as above.
Computerized Adaptive Screen for Suicidal Youth (CASSY) study
Adolescent suicide rates in the United States, partly augmented by the COVID-19 pandemic, are steadily increasing [1, 2]. A commonly used screening tool is the 4-question Ask Suicide-Screening Questions (ASQ) instrument, which has a sensitivity and specificity of 60% and 92.7%, respectively, in predicting suicide-related events within 3 months. This was derived from a retrospective study of 15,003 pediatric patients (age 10-18 years) [3]. Given the morbidity and mortality associated with suicide attempts, is there a better screening tool with a higher sensitivity than 60%, while also maintaining adequate specificity? A higher sensitivity rate ensures that we have fewer misses.
The CASSY tool
In JAMA Psychiatry 2021, the Pediatric Emergency Care Applied Research Network (PECARN) researchers report derivation and external validation data for their suicide screening tool, called the Computerized Adaptive Screen for Suicidal Youth (CASSY) [4]. This publication was actually two studies in one: a derivation of the tool and then an external validation.
Terminology
This paper assumes that the reader understands certain predictive analytics methodologies and test design concepts. Let’s briefly review some of the foundational terminology used:
- Item response theory [Wikipedia]: “It is a theory of testing based on the relationship between individuals’ performances on a test item and the test takers’ levels of performance on an overall measure of the ability that item was designed to measure.” Of note, each item may be weighted differently based on how well it correlates with the overall outcome measure, which in this study was suicide attempt within 3 months.
- Computerized adaptive testing [Wikipedia]: This computer testing strategy, also known as tailored testing, presents questions based on the individual’s response to a prior question.
- Receiver operator characteristics (ROC): “The performance of a diagnostic test in the case of a binary predictor can be evaluated using the measures of sensitivity and specificity. However, in many instances, we encounter predictors that are measured on a continuous or ordinal scale. In such cases, it is desirable to assess performance of a diagnostic test over the range of possible cutpoints for the predictor variable. This is achieved by a receiver operating characteristic (ROC) curve that includes all the possible decision thresholds from a diagnostic test result.” [5] In other words, test sensitivities can be calculated for set specificities of, for instance, 70%, 80%, and 90%. Based on the purpose of the diagnostic test, the binary predictor threshold would be set accordingly.
- Area under the curve (AUC): Calculating the AUC for the ROC is an effective means to determine a diagnostic test’s accuracy. The AUC ranges from 0 to 1 with 0.5 meaning no discrimination (i.e., the test can not diagnose patients with and without the disease based on the test). Generally, an AUC value of 0.7-0.8 is acceptable, 0.8 to 0.9 is excellent, and >0.9 is outstanding [5].
Study 1: CASSY derivation
A total of 6,536 adolescents (age 12-17 years) from 13 PECARN emergency departments were enrolled and a subset were randomly received follow-up in 3 months to assess for a suicide attempt. These patients responded to 92 questions on a computer tablet. Using a multidimensional item response theory approach, the more correlated questions (72) were used to create the CASSY tool.
Test characteristic results:
- AUC: 0.89 (excellent)
- Using the ROC curve, the CASSY sensitivity was 83% and 61% for the fixed specificity of 80% and 90%, respectively.
Study 2: CASSY validation
A total of 4,050 adolescents from 14 PECARN emergency departments were enrolled, and all received 3-month follow-up assessing for a suicide attempt. These patients completed the CASSY tool, as well as a subset of questions from study 1 for comparison. The frequency of questions used in the adaptive screen are itemized in the paper.
Test characteristic results:
- AUC 0.87 (excellent)
- Using the ROC curve and at the 80% specificity cutoff from study 1, the CASSY sensitivity was 82.4% and specificity was 72.5%.
Limitations
Although there was strong study rigor by deriving and independently validating the tool in separate, multicenter populations, it should be noted that generalizability may be affected.
- The study was conducted in academic pediatric emergency departments.
- There was quite a few patients who were lost to follow up (27.1% in study 1, 30.5% in study 2), which may have skewed the results.
- Selection bias may have occurred because of patients declining to participate in the study (62% enrollment rate in study 1, 62.2% in study 2)
Bottom line
The CASSY tool accurately serves as a screening predictive tool for adolescents at risk for a suicide attempt in 3 months. Rather than having patients complete exhaustively long (and practically unfeasible) screening questions in the emergency department, this computerized adaptive tool required only a mean of 11 questions, which took a median time of 1.4 minutes (IQR 0.98-2.06 minutes) to complete.
How can you implement CASSY in your emergency department?
We asked the authors this question, and the answer is in the podcast below.
Podcast
Listen more with author Dr. Jacqueline Grupp-Phelan talking with ALiEM podcast host, Dr. Dina Wallin, about this landmark paper and behind-the-scenes issues not included on the paper.
This blog post was expert peer-reviewed by Drs. King and Grupp-Phelan, who authored the paper.
References
- Hill RM, Rufino K, Kurian S, Saxena J, Saxena K, Williams L. Suicide Ideation and Attempts in a Pediatric Emergency Department Before and During COVID-19 [published online ahead of print, 2020 Dec 16]. Pediatrics. 2020;e2020029280. PMID: 33328339
- Centers for Disease Control and Prevention. Web-based Injury Statistics Query and Reporting System (WISQARS). Published 2020.
- DeVylder JE,Ryan TC, Cwik M, et al. Assessment of selective and universal screening for suicide risk in a pediatric emergency department. JAMA Netw Open. 2019;2(10):e1914070-e1914070. PMID 31651971
- King CA, Brent D, Grupp-Phelan J, et al. Prospective Development and Validation of the Computerized Adaptive Screen for Suicidal Youth [published online ahead of print, 2021 Feb 3]. JAMA Psychiatry. 2021; 10.1001/jamapsychiatry.2020.4576. doi:10.1001/jamapsychiatry.2020.4576. PMID 33533908
- Mandrekar JN. Receiver operating characteristic curve in diagnostic test assessment. J Thorac Oncol. 2010;5(9):1315-1316. doi:10.1097/JTO. 0b013e3181ec173d
Listen to all the PECARN podcasts
SplintER Series: Keep Your Knees Up
A 27-year-old female presents with left knee pain after a low-speed motor vehicle collision in which her knee hit the dashboard. She is tender over the patella without significant effusion and has an intact extensor mechanism. The above x-ray was obtained (Image 1. X-ray left knee. Case courtesy of Dr. M. Mourits, Radiopaedia.org, rID: 14476).
SplintER Series: A Temporary Pain in the Neck
An 18-year-old football player presents to the Emergency Department after an episode of transient numbness, tingling, and inability to move his right upper extremity after making a tackle. He continued playing without recurrence. The above imaging was obtained (Figure 1. Lateral cervical spine x-ray. Case courtesy of Dr Andrew Dixon, Radiopaedia.org, rID: 32505).
SAEM Clinical Image Series: What’s This Thing on My Face?
A 91-year-old female patient presented with her family after concern for multiple new lesions on her face and hands. The patient thinks the lesions grew over the course of a few months. There is no pain at the sites, no erythema, and no pruritis. She has caught the lesions on clothing and bedding, which has irritated the lesions on occasion, and the family is concerned/embarrassed by the growths on her face, which are harder to conceal than those on her hand.
SAEM Clinical Image Series: Guess Who’s Back?
A 27-year-old male with no significant past medical history presented to the emergency department with one week of progressively worsening, non-pruritic, and intermittently painful rash to his bilateral dorsal and plantar feet. The patient also described lesions to his left inguinal region and scrotal sac. There was no fever, chills, nausea, vomiting, chest pain, or shortness of breath. The patient was sexually active with men and women, with inconsistent condom use.
Adverse Events from IV Olanzapine for Agitation in the ED
The ability to safely and effectively sedate agitated patients in the emergency department (ED) is paramount to provide prompt medical care and protect ED staff. Intravenous (IV) antipsychotics are frequently utilized, instead of other routes, given their more rapid onset of action. Similar to haloperidol, olanzapine can be used safely via the IV route despite both being FDA-approved for intramuscular (IM) administration only.
What is the adverse event profile for IV olanzapine when administered for agitation in the ED?
The table below summarizes the primary data evaluating IV olanzapine in the ED [1-5]. While IV olanzapine is a safe option for some agitated patients, some of these studies report a higher risk of respiratory complications or respiratory depression with the IV route compared to IM olanzapine or other IV treatment options. An Annals of Emergency Medicine commentary argues IV olanzapine might not be necessary for non-emergent cases of agitation or non-agitation indications and the IM route may suffice [6].
| Study | Olanzapine Dose | Adverse Event Rate – Olanzapine | Adverse Event Rate – Comparators | Notes |
|---|---|---|---|---|
| Chang 2013 (N=336) |
10 mg | 8.3% | IV Droperidol: 10.7% Placebo: 15.7 % |
|
| Martel 2016 (N=713) |
1.25-20 mg | Minor: 11.4% Major: 2.6% |
N/A | Adverse events were respiratory complications; 7 patients intubated |
| Taylor 2017 (N=92) |
5-10 mg | 20% | IV Midazolam + Droperidol: 22% IV Droperidol: 16.2% |
|
| Yap 2017 (N=92) |
10 mg | 21.4% | IV Midazolam + Droperidol: 20.6% IV Droperidol: 6.7% |
Methamphetamine-induced agitation |
| Cole 2017 (N=784) |
1.25-20 mg | 3.7% | IM olanzapine: 2.0% | Adverse events were respiratory depression |
Table: Adverse Events from IV Olanzapine for Agitation in the ED [1-5]
Treatment of agitated patients in the ED can be complex. Respiratory complications after medication administration may be related directly to the medication(s), the reduction of sympathetic drive, or both. All agitated patients should be monitored after receiving medications for sedation. The exact time course of this monitoring is not known and likely medication specific. Patients at high risk of neurologic, cardiovascular, or hemodynamic compromise should be monitored even more closely. This could include an ECG, pulse oxygenation, vital signs, and direct observation, as appropriate based on the patient-specific factors.
Bottom Line
Medication selection for treating agitation in the ED requires thoughtful consideration of factors such as onset time (read more about “Onset of IM Medications for Severe Agitation“), duration, adverse events, and patient-specific variables. IV olanzapine is an option and monitoring should be commensurate with the situation and medication(s) chosen.
For further information, please read this in-depth literature review of IV olanzapine for the management agitation [7].
Want to learn more about EM Pharmacology?
Read other articles in the EM Pharm Pearls Series and find previous pearls on the PharmERToxguy site.
References
- Chan EW, Taylor DM, Knott JC, Phillips GA, Castle DJ, Kong DCM. Intravenous droperidol or olanzapine as an adjunct to midazolam for the acutely agitated patient: a multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med. 2013;61(1):72-81. doi: 10.1016/j.annemergmed.2012.07.118. PMID: 22981685.
- Martel ML, Klein LR, Rivard RL, Cole JB. A large retrospective cohort of patients receiving intravenous olanzapine in the emergency department. Acad Emerg Med. 2016;23(1):29-35. doi: 10.1111/acem.12842. PMID: 26720055.
- Taylor DM, Yap CYL, Knott JC, et al. Midazolam-droperidol, droperidol, or olanzapine for acute agitation: a randomized clinical trial. Ann Emerg Med. 2017;69(3):318-326.e1. doi: 10.1016/j.annemergmed.2016.07.033. PMID: 27745766.
- Yap CYL, Taylor DM, Knott JC, et al. Intravenous midazolam-droperidol combination, droperidol or olanzapine monotherapy for methamphetamine-related acute agitation: subgroup analysis of a randomized controlled trial. Addiction. 2017;112(7):1262-1269. doi: 10.1111/add.13780. PMID: 28160494.
- Cole JB, Moore JC, Dolan BJ, et al. A prospective observational study of patients receiving intravenous and intramuscular olanzapine in the emergency department. Ann Emerg Med. 2017;69(3):327-336.e2. doi: 10.1016/j.annemergmed.2016.08.008. PMID: 27823873.
- Isbister GK. Droperidol or olanzapine, intramuscularly or intravenously, monotherapy or combination therapy for sedating acute behavioral disturbance. Ann Emerg Med. 2017;69(3):337-339. doi: 10.1016/j.annemergmed.2016.09.021. PMID: 27974168.
- Khorassani F, Saad M. Intravenous olanzapine for the management of agitation: review of the literature. Ann Pharmacother. 2019;53(8):853-859. doi: 10.1177/1060028019831634. PMID: 30758221