Formative evaluation of an emergency department clinical decision support system for agitation symptoms: a study protocol.

INTRODUCTION: The burden of mental health-related visits to emergency departments (EDs) is growing, and agitation episodes are prevalent with such visits. Best practice guidance from experts recommends early assessment of at-risk populations and pre-emptive intervention using de-escalation techniques to prevent agitation. Time pressure, fluctuating work demands, and other systems-related factors pose challenges to efficient decision-making and adoption of best practice recommendations during an unfolding behavioural crisis. As such, we propose to design, develop and evaluate a computerised clinical decision support (CDS) system, Early Detection and Treatment to Reduce Events with Agitation Tool (ED-TREAT). We aim to identify patients at risk of agitation and guide ED clinicians through appropriate risk assessment and timely interventions to prevent agitation with a goal of minimising restraint use and improving patient experience and outcomes. METHODS AND ANALYSIS: This study describes the formative evaluation of the health record embedded CDS tool. Under aim 1, the study will collect qualitative data to design and develop ED-TREAT using a contextual design approach and an iterative user-centred design process. Participants will include potential CDS users, that is, ED physicians, nurses, technicians, as well as patients with lived experience of restraint use for behavioural crisis management during an ED visit. We will use purposive sampling to ensure the full spectrum of perspectives until we reach thematic saturation. Next, under aim 2, the study will conduct a pilot, randomised controlled trial of ED-TREAT at two adult ED sites in a regional health system in the Northeast USA to evaluate the feasibility, fidelity and bedside acceptability of ED-TREAT. We aim to recruit a total of at least 26 eligible subjects under the pilot trial. ETHICS AND DISSEMINATION: Ethical approval by the Yale University Human Investigation Committee was obtained in 2021 (HIC# 2000030893 and 2000030906). All participants will provide informed verbal consent prior to being enrolled in the study. Results will be disseminated through publications in open-access, peer-reviewed journals, via scientific presentations or through direct email notifications. TRIAL REGISTRATION NUMBER: NCT04959279; Pre-results.

An introduction and practical guide to strategies for analyzing longitudinal data in clinical trials of smoking cessation treatment: Beyond dichotomous point-prevalence outcomes.

Conceptualizing tobacco dependence as a chronic relapsing condition suggests the need to use analytic strategies that reflect that premise. However, clinical trials for smoking cessation typically define the primary endpoint as a measure of abstinence at a single timepoint distal to the intervention, typically 3-12 months. This reinforces the concept of tobacco outcomes as a dichotomous state-one is, or is not, abstinent. Fortunately, there are several approaches available to handle longitudinal data that reflect the relapsing and remitting nature of tobacco use during treatment studies. In this paper, sponsored by the Society for Research on Nicotine and Tobacco's Treatment Research Network, we present an introductory overview of these techniques and their application in smoking cessation clinical trials. Topics discussed include models to examine abstinence outcomes (e.g., trajectory models of abstinence, models for transitions in smoking behavior, models for time to event), models that examine reductions in tobacco use, and models to examine joint outcomes (e.g., examining changes in use of more than one tobacco product). Finally, we discuss three additional relevant topics (i.e., heterogeneity of effects, handling missing data, power and sample size) and provide summary information about the type of model that can be used based on the type of data collected and the focus of the study. We encourage investigators to familiarize themselves with these techniques and use them in the analysis of data from clinical trials of smoking cessation treatment. IMPLICATIONS: Clinical trials of tobacco dependence treatment typically measure abstinence 3-12 months after participant enrollment. However, because smoking is a chronic relapsing condition, these measures of intervention success may not accurately reflect the common trajectories of tobacco abstinence and relapse. Several analytical techniques facilitate this type of outcome modeling. This paper is meant to be an introduction to these concepts and techniques to the global nicotine and tobacco research community including which techniques can be used for different research questions with visual summaries of which types of models can be used for different types of data and research questions.

Evaluation of clinical assessments of social abilities for use in autism clinical trials by the autism biomarkers consortium for clinical trials.

Clinical trials in autism spectrum disorder (ASD) often rely on clinician rating scales and parent surveys to measure autism-related features and social behaviors. To aid in the selection of these assessments for future clinical trials, the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) directly compared eight common instruments with respect to acquisition rates, sensitivity to group differences, equivalence across demographic sub-groups, convergent validity, and stability over a 6-week period. The sample included 280 children diagnosed with ASD (65 girls) and 119 neurotypical children (36 girls) aged from 6 to 11 years. Full scale IQ for ASD ranged from 60 to 150 and for neurotypical ranged from 86 to 150. Instruments measured clinician global assessment and autism-related behaviors, social communication abilities, adaptive function, and social withdrawal behavior. For each instrument, we examined only the scales that measured social or communication functioning. Data acquisition rates were at least 97.5% at T1 and 95.7% at T2. All scales distinguished diagnostic groups. Some scales significantly differed by participant and/or family demographic characteristics. Within the ASD group, most clinical instruments exhibited weak (≥ |0.1|) to moderate (≥ |0.4|) intercorrelations. Short-term stability was moderate (ICC: 0.5-0.75) to excellent (ICC: >0.9) within the ASD group. Variations in the degree of stability may inform viability for different contexts of use, such as identifying clinical subgroups for trials versus serving as a modifiable clinical outcome. All instruments were evaluated in terms of their advantages and potential concerns for use in clinical trials.

Racial and ethnic disparities in emergency department-initiated buprenorphine across five health care systems.

BACKGROUND: Opioid overdose deaths have disproportionately impacted Black and Hispanic populations, in part due to disparities in treatment access. Emergency departments (EDs) serve as a resource for patients with opioid use disorder (OUD), many of whom have difficulty accessing outpatient addiction programs. However, inequities in ED treatment for OUD remain poorly understood. METHODS: This secondary analysis examined racial and ethnic differences in buprenorphine access using data from EMBED, a study of 21 EDs across five health care systems evaluating a clinical decision support system for initiating ED buprenorphine. The primary outcome was receipt of buprenorphine, ED administered or prescribed. Hospital type (academic vs. community) was evaluated as an effect modifier. Hierarchical models with cluster effects for site and clinician were used to assess buprenorphine receipt by race and ethnicity. RESULTS: Black patients were less likely to receive buprenorphine (6.4% [51/801] vs. White patients 8.5% [268/3154], odds ratio [OR] 0.59, 95% confidence interval [CI] 0.45-0.78). This association persisted after adjusting for age, insurance, gender, clinician X-waiver, hospital type, and urbanicity (adjusted OR [aOR] 0.64, 95% CI 0.48-0.84) but not when discharge diagnosis was included (aOR 0.75, 95% CI 0.56-1.02). Hispanic patients were more likely to receive buprenorphine (14.8% [122/822] vs. non-Hispanic patients, 11.6% [475/4098]) in unadjusted (OR 1.57, 95% CI 1.09-1.83) and adjusted models (aOR 1.41, 95% CI 1.08-1.83) but not including discharge diagnosis (aOR 1.32, 95% CI 0.99-1.77). Odds of buprenorphine were similar in academic and community EDs by race (interaction p = 0.97) and ethnicity (interaction p = 0.64). CONCLUSIONS: Black patients with OUD were less likely to receive buprenorphine whereas Hispanic patients were more likely to receive buprenorphine in academic and community EDs. Differences were attenuated with discharge diagnosis, as fewer Black and non-Hispanic patients were diagnosed with opioid withdrawal. Barriers to medication treatment are heterogenous among patients with OUD; research must continue to address the multiple drivers of health inequities at the patient, clinician, and community level.

Cost-Effectiveness of Smoking Cessation Approaches in Emergency Departments.

INTRODUCTION: Americans of lower SES use tobacco products at disproportionately high rates and are over-represented as patients of emergency departments. Accordingly, emergency department visits are an ideal time to initiate tobacco treatment and aftercare for this vulnerable and understudied population. This research estimates the costs per quit of emergency department smoking-cessation interventions and compares them with those of other approaches. METHODS: Previously published research described the effectiveness of 2 multicomponent smoking cessation interventions, including brief negotiated interviewing, nicotine replacement therapy, quitline referral, and follow-up communication. Study 1 (collected in 2010-2012) only analyzed the combined interventions. Study 2 (collected in 2017-2019) analyzed the intervention components independently. Costs per participant and per quit were estimated separately, under distinct intervention with dedicated staff and intervention with repurposed staff assumptions. The distinction concerns whether the intervention used dedicated staff for delivery or whether time from existing staff was repurposed for intervention if available. RESULTS: Data were analyzed in 2021-2022. In the first study, the cost per participant was $860 (2018 dollars), and the cost per quit was $11,814 (95% CI=$7,641, $25,423) (dedicated) and $227 per participant and $3,121 per quit (95% CI=$1,910, $7,012) (repurposed). In Study 2, the combined effect of brief negotiated interviewing, nicotine replacement therapy, and quitline cost $808 per participant and $6,100 per quit (dedicated) (95% CI=$4,043, $12,274) and $221 per participant and $1,669 per quit (95% CI=$1,052, $3,531) (repurposed). CONCLUSIONS: Costs varied considerably per method used but were comparable with those of other smoking cessation interventions.

Racial and Ethnic Differences in Internal Medicine Residency Assessments.

Importance: Previous studies have demonstrated racial and ethnic inequities in medical student assessments, awards, and faculty promotions at academic medical centers. Few data exist about similar racial and ethnic disparities at the level of graduate medical education. Objective: To examine the association between race and ethnicity and performance assessments among a national cohort of internal medicine residents. Design, Setting, and Participants: This retrospective cohort study evaluated assessments of performance for 9026 internal medicine residents from the graduating classes of 2016 and 2017 at Accreditation Council of Graduate Medical Education (ACGME)-accredited internal medicine residency programs in the US. Analyses were conducted between July 1, 2020, and June 31, 2022. Main Outcomes and Measures: The primary outcome was midyear and year-end total ACGME Milestone scores for underrepresented in medicine (URiM [Hispanic only; non-Hispanic American Indian, Alaska Native, or Native Hawaiian/Pacific Islander only; or non-Hispanic Black/African American]) and Asian residents compared with White residents as determined by their Clinical Competency Committees and residency program directors. Differences in scores between Asian and URiM residents compared with White residents were also compared for each of the 6 competency domains as supportive outcomes. Results: The study cohort included 9026 residents from 305 internal medicine residency programs. Of these residents, 3994 (44.2%) were female, 3258 (36.1%) were Asian, 1216 (13.5%) were URiM, and 4552 (50.4%) were White. In the fully adjusted model, no difference was found in the initial midyear total Milestone scores between URiM and White residents, but there was a difference between Asian and White residents, which favored White residents (mean [SD] difference in scores for Asian residents: -1.27 [0.38]; P < .001). In the second year of training, White residents received increasingly higher scores relative to URiM and Asian residents. These racial disparities peaked in postgraduate year (PGY) 2 (mean [SD] difference in scores for URiM residents, -2.54 [0.38]; P < .001; mean [SD] difference in scores for Asian residents, -1.9 [0.27]; P < .001). By the final year 3 assessment, the gap between White and Asian and URiM residents' scores narrowed, and no racial or ethnic differences were found. Trends in racial and ethnic differences among the 6 competency domains mirrored total Milestone scores, with differences peaking in PGY2 and then decreasing in PGY3 such that parity in assessment was reached in all competency domains by the end of training. Conclusions and Relevance: In this cohort study, URiM and Asian internal medicine residents received lower ratings on performance assessments than their White peers during the first and second years of training, which may reflect racial bias in assessment. This disparity in assessment may limit opportunities for physicians from minoritized racial and ethnic groups and hinder physician workforce diversity.

User centered clinical decision support to implement initiation of buprenorphine for opioid use disorder in the emergency department: EMBED pragmatic cluster randomized controlled trial.

OBJECTIVE: To determine the effect of a user centered clinical decision support tool versus usual care on rates of initiation of buprenorphine in the routine emergency care of individuals with opioid use disorder. DESIGN: Pragmatic cluster randomized controlled trial (EMBED). SETTING: 18 emergency department clusters across five healthcare systems in five states representing the north east, south east, and western regions of the US, ranging from community hospitals to tertiary care centers, using either the Epic or Cerner electronic health record platform. PARTICIPANTS: 599 attending emergency physicians caring for 5047 adult patients presenting with opioid use disorder. INTERVENTION: A user centered, physician facing clinical decision support system seamlessly integrated into user workflows in the electronic health record to support initiating buprenorphine in the emergency department by helping clinicians to diagnose opioid use disorder, assess the severity of withdrawal, motivate patients to accept treatment, and complete electronic health record tasks by automating clinical and after visit documentation, order entry, prescribing, and referral. MAIN OUTCOME MEASURES: Rate of initiation of buprenorphine (administration or prescription of buprenorphine) in the emergency department among patients with opioid use disorder. Secondary implementation outcomes were measured with the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework. RESULTS: 1 413 693 visits to the emergency department (775 873 in the intervention arm and 637 820 in the usual care arm) from November 2019 to May 2021 were assessed for eligibility, resulting in 5047 patients with opioid use disorder (2787 intervention arm, 2260 usual care arm) under the care of 599 attending physicians (340 intervention arm, 259 usual care arm) for analysis. Buprenorphine was initiated in 347 (12.5%) patients in the intervention arm and in 271 (12.0%) patients in the usual care arm (adjusted generalized estimating equations odds ratio 1.22, 95% confidence interval 0.61 to 2.43, P=0.58). Buprenorphine was initiated at least once by 151 (44.4%) physicians in the intervention arm and by 88 (34.0%) in the usual care arm (1.83, 1.16 to 2.89, P=0.01). CONCLUSIONS: User centered clinical decision support did not increase patient level rates of initiating buprenorphine in the emergency department. Although streamlining and automating electronic health record workflows can potentially increase adoption of complex, unfamiliar evidence based practices, more interventions are needed to look at other barriers to the treatment of addiction and increase the rate of initiating buprenorphine in the emergency department in patients with opioid use disorder. TRIAL REGISTRATION: ClinicalTrials.gov NCT03658642.

Improving patient and clinician safety during COVID-19 through rapidly adaptive simulation and a randomised controlled trial: a study protocol.

INTRODUCTION: COVID-19 required healthcare systems to iteratively adapt for safe and up-to-date care as knowledge of the disease rapidly evolved. Rates of COVID-19 infections continue to fluctuate and patients without COVID-19 increasingly return to the emergency department (ED) for care. This leads to new challenges and threats to patient and clinician safety as suspected patients with COVID-19 need to be quickly detected and isolated among other patients with non-COVID-19-related illnesses. At the front lines, emergency physicians also face continued personal safety concerns and increased work burden, which heighten stress and anxiety, especially given the prolonged course of the pandemic. Burnout, already a serious concern for emergency physicians due to the cumulative stresses of their daily practice, may present as a longer-term outcome of these acute stressors. METHODS AND ANALYSIS: We will implement a rapidly adaptive simulation-based approach to understand and improve physician preparedness while decreasing physician stress and anxiety. First, we will conduct semi-structured qualitative interviews and human factor observations to determine the challenges and facilitators of COVID-19 preparedness and mitigation of physician stress. Next, we will conduct a randomised controlled trial to test the effectiveness of a simulation preparedness intervention on physician physiological stress as measured by decreased heart rate variability on shift and anxiety as measured by the State-Trait Anxiety Inventory. ETHICS AND DISSEMINATION: The protocol was reviewed and approved by the Agency for Healthcare Research and Quality for funding, and ethics approval was obtained from the Yale University Human Investigation Committee in 2020 (HIC# 2000029370 and 2000029372). To support ongoing efforts to address clinician stress and preparedness, we will strategically disseminate the simulation intervention to areas most impacted by COVID-19. Using a virtual telesimulation and webinar format, the dissemination efforts will provide hands-on learning for ED and hospital administrators as well as simulation educators. TRIAL REGISTRATION NUMBER: NCT04614844.

Impact of complex, partially nested clustering in a three-arm individually randomized group treatment trial: A case study with the wHOPE trial.

BACKGROUND/AIMS: When participants in individually randomized group treatment trials are treated by multiple clinicians or in multiple group treatment sessions throughout the trial, this induces partially nested clusters which can affect the power of a trial. We investigate this issue in the Whole Health Options and Pain Education trial, a three-arm pragmatic, individually randomized clinical trial. We evaluate whether partial clusters due to multiple visits delivered by different clinicians in the Whole Health Team arm and dynamic participant groups due to changing group leaders and/or participants across treatment sessions during treatment delivery in the Primary Care Group Education arm may impact the power of the trial. We also present a Bayesian approach to estimate the intraclass correlation coefficients. METHODS: We present statistical models for each treatment arm of Whole Health Options and Pain Education trial in which power is estimated under different intraclass correlation coefficients and mapping matrices between participants and clinicians or treatment sessions. Power calculations are based on pairwise comparisons. In practice, sample size calculations depend on estimates of the intraclass correlation coefficients at the treatment sessions and clinician levels. To accommodate such complexities, we present a Bayesian framework for the estimation of intraclass correlation coefficients under different participant-to-session and participant-to-clinician mapping scenarios. We simulated continuous outcome data based on various clinical scenarios in Whole Health Options and Pain Education trial using a range of intraclass correlation coefficients and mapping matrices and used Gibbs samplers with conjugate priors to obtain posteriors of the intraclass correlation coefficients under those different scenarios. Posterior means and medians and their biases are calculated for the intraclass correlation coefficients to evaluate the operating characteristics of the Bayesian intraclass correlation coefficient estimators. RESULTS: Power for Whole Health Team versus Primary Care Group Education is sensitive to the intraclass correlation coefficient in the Whole Health Team arm. In these two arms, an increased number of clinicians, more evenly distributed workload of clinicians, or more homogeneous treatment group sizes leads to increased power. Our simulation study for the intraclass correlation coefficient estimation indicates that the posterior mean intraclass correlation coefficient estimator has less bias when the true intraclass correlation coefficients are large (i.e. 0.10), but when the intraclass correlation coefficient is small (i.e. 0.01), the posterior median intraclass correlation coefficient estimator is less biased. CONCLUSION: Knowledge of intraclass correlation coefficients and the structure of clustering are critical to the design of individually randomized group treatment trials with partially nested clusters. We demonstrate that the intraclass correlation coefficient of the Whole Health Team arm can affect power in the Whole Health Options and Pain Education trial. A Bayesian approach provides a flexible procedure for estimating the intraclass correlation coefficients under complex scenarios. More work is needed to educate the research community about the individually randomized group treatment design and encourage publication of intraclass correlation coefficients to help inform future trial designs.

Design and Implementation of an Agitation Code Response Team in the Emergency Department.

STUDY OBJECTIVE: Agitation, defined as excessive psychomotor activity leading to violent and aggressive behavior, is becoming more prevalent in the emergency department (ED) amidst a strained behavioral health system. Team-based interventions have demonstrated promise in promoting de-escalation, with the hope of minimizing the need for invasive techniques, like physical restraints. This study aimed to evaluate an interprofessional code response team intervention to manage agitation in the ED with the goal of decreasing physical restraint use. METHODS: This quality improvement study occurred over 3 phases, representing stepwise rollout of the intervention: (1) preimplementation (phase I) to establish baseline outcome rates; (2) design and administrative support (phase II) to conduct training and protocol design; and (3) implementation (phase III) of the code response team. An interrupted time-series analysis was used to compare trends between phases to evaluate the primary outcome of physical restraint orders occurring during the study period. RESULTS: Within the 634,578 ED visits over a 5-year period, restraint use significantly declined sequentially over the 3 phases (1.1%, 0.9%, and 0.8%, absolute change -0.3% between phases I and III, 95% confidence interval [CI] -0.4% to 0.3%), which corresponded to a 27.3% proportionate decrease in restraint rates between phases I and III. For the interrupted time-series analysis, there was a significantly decreasing slope in biweekly restraints in phase II compared to phase I (slope, -0.05 restraints per 1,000 ED visits per 2-week period, 95% CI -0.07 to -0.03), which was sustained in an incremental fashion in phase III (slope, -0.05, 95% CI -0.07 to -0.02). CONCLUSION: With the implementation of a structured agitation code response team intervention combined with design and administrative support, a decreased rate of physical restraint use occurred over a 5-year period. Results suggest that investment in organizational change, along with interprofessional collaboration during the management of agitated patients in the ED, can lead to sustained reductions in the use of an invasive and potentially harmful measure on patients.

Variations in Quality of Care by Sex and Social Determinants of Health Among Younger Adults With Acute Myocardial Infarction in the US and Canada.

Importance: Quality of care of young adults with acute myocardial infarction (AMI) may depend on health care systems in addition to individual-level factors such as biological sex and social determinants of health (SDOH). Objective: To examine whether the quality of in-hospital and postacute care among young adults with AMI differs between the US and Canada and whether female sex and adverse SDOH are associated with a low quality of care. Design, Setting, and Participants: This retrospective cohort analysis used data from 2 large cohorts of young adults (aged ≤55 years) receiving in-hospital and outpatient care for AMI at 127 centers in the US and Canada. Data were collected from August 21, 2008, to April 30, 2013, and analyzed from July 12, 2019, to March 10, 2021. Exposures: Sex, SDOH, and health care system. Main Outcomes and Measures: Opportunity-based quality-of-care score (QCS), determined by dividing the total number of quality indicators of care received by the total number for which the patient was eligible, with low quality of care defined as the lowest tertile of the QCS. Results: A total of 4048 adults with AMI (2345 women [57.9%]; median age, 49 [interquartile range, 44-52] years; 3004 [74.2%] in the US) were included in the analysis. Of 3416 patients with in-hospital QCS available, 1061 (31.1%) received a low QCS, including more women compared with men (725 of 2007 [36.1%] vs 336 of 1409 [23.8%]; P < .001) and more patients treated in the US vs Canada (962 of 2646 [36.4%] vs 99 of 770 [12.9%]; P < .001). Conversely, low quality of post-AMI care (748 of 2938 [25.5%]) was similarly observed for both sexes, with a higher prevalence in the US (678 of 2346 [28.9%] vs 70 of 592 [11.8%]). In adjusted analyses, female sex was not associated with low QCS for in-hospital (odds ratio [OR], 1.05; 95% CI, 0.87-1.28) and post-AMI (OR, 1.07; 95% CI, 0.88-1.30) care. Conversely, being treated in the US was associated with low in-hospital (OR, 2.93; 95% CI, 2.16-3.99) and post-AMI (OR, 2.67; 95% CI, 1.97-3.63) QCS, regardless of sex. Of all SDOH, only employment was associated with higher quality of in-hospital care (OR, 0.72; 95% CI, 0.59-0.88). Finally, only in the US, low quality of in-hospital care was associated with a higher 1-year cardiac readmissions rate (234 of 962 [24.3%]). Conclusions and Relevance: These findings suggest that beyond sex, health care systems and SDOH that depict social vulnerability are associated with quality of AMI care. Taking into account SDOH among young adults with AMI may improve quality of care and reduce readmissions, especially in the US.

A case study of ascertainment bias for the primary outcome in the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial.

BACKGROUND/AIM: In clinical trials, there is potential for bias from unblinded observers that may influence ascertainment of outcomes. This issue arose in the Strategies to Reduce Injuries and Develop Confidence in Elders trial, a cluster randomized trial to test a multicomponent intervention versus enhanced usual care (control) to prevent serious fall injuries, originally defined as a fall injury leading to medical attention. An unblinded nurse falls care manager administered the intervention, while the usual care arm did not involve contact with a falls care manager. Thus, there was an opportunity for falls care managers to refer participants reporting falls to seek medical attention. Since this type of observer bias could not occur in the usual care arm, there was potential for additional falls to be reported in the intervention arm, leading to dilution of the intervention effect and a reduction in study power. We describe the clinical basis for ascertainment bias, the statistical approach used to assess it, and its effect on study power. METHODS: The prespecified interim monitoring plan included a decision algorithm for assessing ascertainment bias and adapting (revising) the primary outcome definition, if necessary. The original definition categorized serious fall injuries requiring medical attention into Type 1 (fracture other than thoracic/lumbar vertebral, joint dislocation, cut requiring closure) and Type 2 (head injury, sprain or strain, bruising or swelling, other). The revised definition, proposed by the monitoring plan, excluded Type 2 injuries that did not necessarily require an overnight hospitalization since these would be most subject to bias. These injuries were categorized into those with (Type 2b) and without (Type 2c) medical attention. The remaining Type 2a injuries required medical attention and an overnight hospitalization. We used the ratio of 2b/(2b + 2c) in intervention versus control as a measure of ascertainment bias; ratios > 1 indicated the likelihood of falls care manager bias. We determined the effect of ascertainment bias on study power for the revised (Types 1 and 2a) versus original definition (Types 1, 2a, and 2b). RESULTS: The estimate of ascertainment bias was 1.14 (95% confidence interval: 0.98, 1.30), providing evidence of the likelihood of falls care manager bias. We estimated that this bias diluted the hazard ratio from the hypothesized 0.80 to 0.86 and reduced power to under 80% for the original primary outcome definition. In contrast, adapting the revised definition maintained study power at nearly 90%. CONCLUSION: There was evidence of ascertainment bias in the Strategies to Reduce Injuries and Develop Confidence in Elders trial. The decision to adapt the primary outcome definition reduced the likelihood of this bias while preserving the intervention effect and study power.

Study protocol for the ACT response pilot intervention: development, implementation and evaluation of a systems-based Agitation Code Team (ACT) in the emergency department.

INTRODUCTION: Emergency department (ED) visits for behavioural conditions are rising, with 1.7 million associated episodes of patient agitation occurring annually in acute care settings. When de-escalation techniques fail during agitation management, patients are subject to use of physical restraints and sedatives, which are associated with up to 37% risk of hypotension, apnoea and physical injuries. At the same time, ED staff report workplace violence due to physical assaults during agitation events. We recently developed a theoretical framework to characterise ED agitation, which identified teamwork as a critical component to reduce harm. Currently, no structured team response protocol for ED agitation addressing both patient and staff safety exists. METHODS AND ANALYSIS: Our proposed study aims to develop and implement the agitation code team (ACT) response intervention, which will consist of a standardised, structured process with defined health worker roles/responsibilities, work processes and clinical protocols. First, we will develop the ACT response intervention in a two-step design loop; conceptual design will engage users in the creation of the prototype, and iterative refinement will occur through in situ simulated agitated patient encounters in the ED to assess and improve the design. Next, we will pilot the intervention in the clinical environment and use a controlled interrupted time series design to evaluate its effect on our primary outcome of patient restraint use. The intervention will be considered efficacious if we effectively lower the rate of restraint use over a 6-month period. ETHICS AND DISSEMINATION: Ethical approval by the Yale University Human Investigation Committee was obtained in 2019 (HIC #2000025113). Results will be disseminated through peer-reviewed publications and presentations at scientific meetings for each phase of the study. If this pilot is successful, we plan to formally integrate the ACT response intervention into clinical workflows at all EDs within our entire health system.

Progress Report on EMBED: A Pragmatic Trial of User-Centered Clinical Decision Support to Implement EMergency Department-Initiated BuprenorphinE for Opioid Use Disorder.

Buprenorphine (BUP) can safely and effectively reduce craving, overdose, and mortality rates in people with opioid use disorder (OUD). However, adoption of ED-initiation of BUP has been slow partly due to physician perception this practice is too complex and disruptive. We report progress of the ongoing EMBED (EMergency department-initiated BuprenorphinE for opioid use Disorder) project. This project is a five-year collaboration across five healthcare systems with the goal to develop, integrate, study, and disseminate user-centered Clinical Decision Support (CDS) to promote the adoption of Emergency Department (ED)-initiation of buprenorphine/naloxone (BUP) into routine emergency care. Soon to enter its third year, the project has already completed multiple milestones to achieve its goals including (1) user-centered design of the CDS prototype, (2) integration of the CDS into an automated electronic health record (EHR) workflow, (3) data coordination including derivation and validation of an EHR-based computable phenotype, (4) meeting all ethical and regulatory requirements to achieve a waiver of informed consent, (5) pilot testing of the intervention at a single site, and (6) launching a parallel group-randomized 18-month pragmatic trial in 20 EDs across 5 healthcare systems. Pilot testing of the intervention in a single ED was associated with increased rates of ED-initiated BUP and naloxone prescribing and a doubling of the number of unique physicians adopting the practice. The ongoing multi-center pragmatic trial will assess the intervention's effectiveness, scalability, and generalizability with a goal to shift the emergency care paradigm for OUD towards early identification and treatment. TRIAL REGISTRATION: Clinicaltrials.gov # NCT03658642.

The Autism Biomarkers Consortium for Clinical Trials (ABC-CT): Scientific Context, Study Design, and Progress Toward Biomarker Qualification.

Clinical research in neurodevelopmental disorders remains reliant upon clinician and caregiver measures. Limitations of these approaches indicate a need for objective, quantitative, and reliable biomarkers to advance clinical research. Extant research suggests the potential utility of multiple candidate biomarkers; however, effective application of these markers in trials requires additional understanding of replicability, individual differences, and intra-individual stability over time. The Autism Biomarkers Consortium for Clinical Trials (ABC-CT) is a multi-site study designed to investigate a battery of electrophysiological (EEG) and eye-tracking (ET) indices as candidate biomarkers for autism spectrum disorder (ASD). The study complements published biomarker research through: inclusion of large, deeply phenotyped cohorts of children with ASD and typical development; a longitudinal design; a focus on well-evidenced candidate biomarkers harmonized with an independent sample; high levels of clinical, regulatory, technical, and statistical rigor; adoption of a governance structure incorporating diverse expertise in the ASD biomarker discovery and qualification process; prioritization of open science, including creation of a repository containing biomarker, clinical, and genetic data; and use of economical and scalable technologies that are applicable in developmental populations and those with special needs. The ABC-CT approach has yielded encouraging results, with one measure accepted into the FDA's Biomarker Qualification Program to date. Through these advances, the ABC-CT and other biomarker studies in progress hold promise to deliver novel tools to improve clinical trials research in ASD.

Identifying Opioid Use Disorder in the Emergency Department: Multi-System Electronic Health Record-Based Computable Phenotype Derivation and Validation Study.

BACKGROUND: Deploying accurate computable phenotypes in pragmatic trials requires a trade-off between precise and clinically sensical variable selection. In particular, evaluating the medical encounter to assess a pattern leading to clinically significant impairment or distress indicative of disease is a difficult modeling challenge for the emergency department. OBJECTIVE: This study aimed to derive and validate an electronic health record-based computable phenotype to identify emergency department patients with opioid use disorder using physician chart review as a reference standard. METHODS: A two-algorithm computable phenotype was developed and evaluated using structured clinical data across 13 emergency departments in two large health care systems. Algorithm 1 combined clinician and billing codes. Algorithm 2 used chief complaint structured data suggestive of opioid use disorder. To evaluate the algorithms in both internal and external validation phases, two emergency medicine physicians, with a third acting as adjudicator, reviewed a pragmatic sample of 231 charts: 125 internal validation (75 positive and 50 negative), 106 external validation (56 positive and 50 negative). RESULTS: Cohen kappa, measuring agreement between reviewers, for the internal and external validation cohorts was 0.95 and 0.93, respectively. In the internal validation phase, Algorithm 1 had a positive predictive value (PPV) of 0.96 (95% CI 0.863-0.995) and a negative predictive value (NPV) of 0.98 (95% CI 0.893-0.999), and Algorithm 2 had a PPV of 0.8 (95% CI 0.593-0.932) and an NPV of 1.0 (one-sided 97.5% CI 0.863-1). In the external validation phase, the phenotype had a PPV of 0.95 (95% CI 0.851-0.989) and an NPV of 0.92 (95% CI 0.807-0.978). CONCLUSIONS: This phenotype detected emergency department patients with opioid use disorder with high predictive values and reliability. Its algorithms were transportable across health care systems and have potential value for both clinical and research purposes.

User-centred clinical decision support to implement emergency department-initiated buprenorphine for opioid use disorder: protocol for the pragmatic group randomised EMBED trial.

INTRODUCTION: The goal of this trial is to determine whether implementation of a user-centred clinical decision support (CDS) system can increase adoption of initiation of buprenorphine (BUP) into the routine emergency care of individuals with opioid use disorder (OUD). METHODS: A pragmatic cluster randomised trial is planned to be carried out in 20 emergency departments (EDs) across five healthcare systems over 18 months. The intervention consists of a user-centred CDS integrated into ED clinician electronic workflow and available for guidance to: (1) determine whether patients presenting to the ED meet criteria for OUD, (2) assess withdrawal symptoms and (3) ascertain and motivate patient willingness to initiate treatment. The CDS guides the ED clinician to initiate BUP and facilitate follow-up. The primary outcome is the rate of BUP initiated in the ED. Secondary outcomes are: (1) rates of receiving a referral, (2) fidelity with the CDS and (3) rates of clinicians providing any ED-initiated BUP, referral for ongoing treatment and receiving Drug Addiction Act of 2000 training. Primary and secondary outcomes will be analysed using generalised linear mixed models, with fixed effects for intervention status (CDS vs usual care), prespecified site and patient characteristics, and random effects for study site. ETHICS AND DISSEMINATION: The protocol has been approved by the Western Institutional Review Board. No identifiable private information will be collected from patients. A waiver of informed consent was obtained for the collection of data for clinician prescribing and other activities. As a minimal risk implementation study of established best practices, an Independent Study Monitor will be utilised in place of a Data Safety Monitoring Board. Results will be reported in ClinicalTrials.gov and published in open-access, peer-reviewed journals, presented at national meetings and shared with the clinicians at participating sites via a broadcast email notification of publications. TRIAL REGISTRATION NUMBER: NCT03658642; Pre-results.

Use of non-face-to-face modalities for emergency department screening, brief intervention, and referral to treatment (ED-SBIRT) for high-risk alcohol use: A scoping review.

Background: The purpose of this review was to examine and chart the "scope" of strategies reported in ED-SBIRT (emergency department-based screening, brief intervention and referral to treatment) studies that employ non-face-to-face (nFtF) modalities for high-risk alcohol use (i.e., risk for alcohol-related injury, medical condition, use disorder) and to identify research gaps in the scientific literature. Methods: The scoping review population included study participants with high-risk alcohol use patterns as well as study participants targeted for primary public health prevention (e.g., adolescent ED patients). Core concepts included SBIRT components among intervention studies that incorporated some form of nFtF modality (e.g., computer-assisted brief intervention). The context encompassed ED-based studies or trauma center studies, regardless of geographic location. After screening a total of 1526 unique references, reviewers independently assessed 58 full-text articles for eligibility. Results: A total of 30 full-text articles were included. Articles covered a period of 14 years (2003-2016) and 19 journal titles. Authors reported the use of a wide range of nFtF modalities across all 3 ED-SBIRT components: "screening" (e.g., computer tablet screening), "brief intervention" (e.g., text message-based brief interventions), and "referral to treatment" (e.g., computer-generated feedback with information about alcohol treatment services). The most frequently used nFtF modality was computerized screening and/or baseline assessment. The main results were mixed with respect to showing evidence of ED-SBIRT intervention effects. Conclusions: There is an opportunity for substance use disorder researchers to explore the specific needs of several populations (e.g., ED patients with co-occurring problems such as substance use disorder and violence victimization) and on several methodological issues (e.g., ED-SBIRT theory of change). Substance use disorder researchers should take the lead on establishing guidelines for the reporting of ED-SBIRT studies-including categorization schemes for various nFtF modalities. This would facilitate both secondary research (e.g., meta-analyses) and primary research design.

Development and Feasibility Testing of a Videogame Intervention to Reduce High-Risk Sexual Behavior in Black and Hispanic Adolescents.

Objective: Develop and test feasibility of a mobile videogame intervention to decrease high-risk sexual behavior in black and Hispanic adolescents. Materials and Methods: Iterative design to develop intervention in partnership with target audience. Feasibility and preliminary impact data collected at baseline, following 2-3 hours of gameplay and at 8-week follow-up. Results: Twenty-six 15-17-year-olds completed pilot testing: 16 (62%) were male, 20 (77%) black or Hispanic. Pilot testing demonstrated feasibility, including producing a usable videogame prototype, incorporating videogame testing within a high school, and participants' acceptability of the videogame. Participants' gameplay experience reflected that most would play the videogame again (77%), stated that they felt responsible for the choices they made in the videogame (73%), and would tell their friends to play the videogame (58%). Most suggested adding more videogame content to further engage participants. From baseline to follow-up, participants demonstrated improvements in condom and contraception self-efficacy (P = 0.003), risk perceptions (P = 0.009), and high-risk sexual behavior knowledge (P < 0.0001). Among black or Hispanic adolescents, we found improvements in summary measures of intentions (P = 0.04), self-efficacy (P = 0.003), risk perceptions (P = 0.002), and sexual knowledge (P = 0.0002). Adolescents with previous sexual experience showed similar improvements. Conclusion: Pilot testing of an innovative videogame, developed in partnership with the target audience, demonstrated feasibility and preliminary impact with this cohort of black or Hispanic adolescents. We developed a usable videogame prototype and gained important data about how to enhance the next videogame iteration. Future plans include targeting an older age group to maximize our ability to measure potential impact among sexually experienced adolescents.