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 (eg, 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 (eg, examining changes in the use of more than one tobacco product). Finally, we discuss three additional relevant topics (ie, heterogeneity of effects, handling missing data, and 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.

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.

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.

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.

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.

Impact of Cost Display on Ordering Patterns for Hospital Laboratory and Imaging Services.

BACKGROUND: Physicians "purchase" many health care services on behalf of patients yet remain largely unaware of the costs of these services. Electronic health record (EHR) cost displays may facilitate cost-conscious ordering of health services. OBJECTIVE: To determine whether displaying hospital lab and imaging order costs is associated with changes in the number and costs of orders placed. DESIGN: Quasi-experimental study. PARTICIPANTS: All patients with inpatient or observation encounters across a multi-site health system from April 2013 to October 2015. INTERVENTION: Display of order costs, based on Medicare fee schedules, in the EHR for 1032 lab tests and 1329 imaging tests. MAIN MEASURES: Outcomes for both lab and imaging orders were (1) whether an order was placed during a hospital encounter, (2) whether an order was placed on a given patient-day, (3) number of orders placed per patient-day, and (4) cost of orders placed per patient-day. KEY RESULTS: During the lab and imaging study periods, there were 248,214 and 258,267 encounters, respectively. Cost display implementation was associated with a decreased odds of any lab or imaging being ordered during the encounter (lab adjusted odds ratio [AOR] = 0.97, p = .01; imaging AOR = 0.97, p < .001), a decreased odds of any lab or imaging being ordered on a given patient-day (lab AOR = 0.95, p < .001; imaging AOR = 0.97, p < .001), a decreased number of lab or imaging orders on patient-days with orders (lab adjusted count ratio = 0.93, p < .001; imaging adjusted count ratio = 0.98, p < .001), and a decreased cost of lab orders and increased cost of imaging orders on patient-days with orders (lab adjusted cost ratio = 0.93, p < .001; imaging adjusted cost ratio = 1.02, p = .003). Overall, the intervention was associated with an 8.5 and 1.7% reduction in lab and imaging costs per patient-day, respectively. CONCLUSIONS: Displaying costs within EHR ordering screens was associated with decreases in the number and costs of lab and imaging orders.

Video Game Intervention for Sexual Risk Reduction in Minority Adolescents: Randomized Controlled Trial.

BACKGROUND: Human immunodeficiency virus (HIV) disproportionately impacts minority youth. Interventions to decrease HIV sexual risk are needed. OBJECTIVE: We hypothesized that an engaging theory-based digital health intervention in the form of an interactive video game would improve sexual health outcomes in adolescents. METHODS: Participants aged 11 to 14 years from 12 community afterschool, school, and summer programs were randomized 1:1 to play up to 16 hours of an experimental video game or control video games over 6 weeks. Assessments were conducted at 6 weeks and at 3, 6, and 12 months. Primary outcome was delay of initiation of vaginal/anal intercourse. Secondary outcomes included sexual health attitudes, knowledge, and intentions. We examined outcomes by gender and age. RESULTS: A total of 333 participants were randomized to play the intervention (n=166) or control games (n=167): 295 (88.6%) were racial/ethnic minorities, 177 (53.2%) were boys, and the mean age was 12.9 (1.1) years. At 12 months, for the 258 (84.6%) participants with available data, 94.6% (122/129) in the intervention group versus 95.4% (123/129) in the control group delayed initiation of intercourse (relative risk=0.99, 95% CI 0.94-1.05, P=.77). Over 12 months, the intervention group demonstrated improved sexual health attitudes overall compared to the control group (least squares means [LS means] difference 0.37, 95% CI 0.01-0.72, P=.04). This improvement was observed in boys (LS means difference 0.67, P=.008), but not girls (LS means difference 0.06, P=.81), and in younger (LS means difference 0.71, P=.005), but not older participants (LS means difference 0.03, P=.92). The intervention group also demonstrated increased sexual health knowledge overall (LS means difference 1.13, 95% CI 0.64-1.61, P<.001), in girls (LS means difference 1.16, P=.001), boys (LS means difference 1.10, P=.001), younger (LS means difference 1.18, P=.001), and older (LS means difference=1.08, P=.002) participants. There were no differences in intentions to delay the initiation of intercourse between the two groups (LS means difference 0.10, P=.56). CONCLUSIONS: An interactive video game intervention improves sexual health attitudes and knowledge in minority adolescents for at least 12 months. TRIAL REGISTRATION: Clinicaltrials.gov NCT01666496; https://clinicaltrials.gov/ct2/show/NCT01666496 (Archived by WebCite at http://www.webcitation.org/6syumc9C0).

Trends in Any and High-Dose Opioid Analgesic Receipt Among Aging Patients With and Without HIV.

Harms of opioid analgesics, especially high-dose therapy among individuals with comorbidities and older age, are increasingly recognized. However, trends in opioid receipt among HIV-infected patients are not well characterized. We examined trends, from 1999 to 2010, in any and high-dose (≥120 mg/day) opioid receipt among patients with and without HIV, by age strata, controlling for demographic and clinical correlates. Of 127,216 patients, 64 % received at least one opioid prescription. Opioid receipt increased substantially among HIV-infected and uninfected patients over the study; high-dose therapy was more prevalent among HIV-infected patients. Trends in high-dose receipt stratified by three age groups revealed an increasing trend in each age strata, higher among HIV-infected patients. Correlates of any opioid receipt included HIV, PTSD and major depression. Correlates of high-dose receipt included HIV, PTSD, major depression and drug use disorders. These findings suggest a need for appropriate balance of risks and benefits, especially as these populations age.

The design and implementation of a randomized controlled trial of a risk reduction and human immunodeficiency virus prevention videogame intervention in minority adolescents: PlayForward: Elm City Stories.

BACKGROUND: To address the need for risk behavior reduction and human immunodeficiency virus prevention interventions that capture adolescents "where they live," we created a tablet-based videogame to teach skills and knowledge and influence psychosocial antecedents for decreasing risk and preventing human immunodeficiency virus infection in minority youth in schools, after-school programs, and summer camps. METHODS: We developed PlayForward: Elm City Stories over a 2-year period, working with researchers, commercial game designers, and staff and teens from community programs. The videogame PlayForward provides an interactive world where players, using an avatar, "travel" through time, facing challenges such as peer pressure to drink alcohol or engage in risky sexual behaviors. Players experience how their choices affect their future and then are able to go back in time and change their choices, creating different outcomes. A randomized controlled trial was designed to evaluate the efficacy of PlayForward. Participants were randomly assigned to play PlayForward or a set of attention/time control games on a tablet at their community-based program. Assessment data were collected during face-to-face study visits and entered into a web-based platform and unique real-time "in-game" PlayForward data were collected as players engaged in the game. The innovative methods of this randomized controlled trial are described. We highlight the logistical issues of conducting a large-scale trial using mobile technology such as the iPad(®), and collecting, transferring, and storing large amounts of in-game data. We outline the methods used to analyze the in-game data alone and in conjunction with standardized assessment data to establish correlations between behaviors during gameplay and those reported in real life. We also describe the use of the in-game data as a measure of fidelity to the intervention. RESULTS: In total, 333 boys and girls, aged 11-14 years, were randomized over a 14-month period: 166 were assigned to play PlayForward and 167 to play the control games. To date (as of 1 March 2016), 18 have withdrawn from the study; the following have completed the protocol-defined assessments: 6 weeks: 271 (83%), 3 months: 269 (84%), 6 months: 254 (79%), 12 months: 259 (82%), and 24 months: is ongoing with 152 having completed out of the 199 participants (76%) who were eligible to date (assessment windows were still open). CONCLUSION: Videogames can be developed to address complex behaviors and can be subject to empiric testing using community-based randomized controlled trials. Although mobile technologies pose challenges in their use as interventions and in the collection and storage of data they produce, they provide unique opportunities as new sources of potentially valid data and novel methods to measure the fidelity of digitally delivered behavioral interventions.

Ethyl glucuronide and ethyl sulfate assays in clinical trials, interpretation, and limitations: results of a dose ranging alcohol challenge study and 2 clinical trials.

BACKGROUND: The ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), are biomarkers of recent alcohol consumption that provide objective measures of abstinence. Our goals are to better understand the impact of cutoff concentration on test interpretation, the need for measuring both metabolites, and how best to integrate test results with self-reports in clinical trials. METHODS: Subjects (n = 18) were administered, 1 week apart, 3 alcohol doses calibrated to achieve blood concentrations of 20, 80, and 120 mg/dl, respectively. Urinary EtG/EtS was measured at timed intervals during a 24-hour hospitalization and twice daily thereafter. In addition, participants from 2 clinical trials provided samples for EtG/EtS and drinking histories. Cutoffs for EtG/EtS of 100/50, 200/100, and 500/250 ng/ml were evaluated. RESULTS: Twelve hours following each challenge, EtG was always positive at the 100 and 200 cutoffs, but at 24 hours sensitivity was poor at all cutoffs following the low dose, and poor after 48 hours regardless of dose or cutoff. Similarly, in the clinical trials EtG sensitivity was good for detecting any drinking during the last 24 hours at the 2 lowest cutoffs, but under 40% during the last 24 to 48 hours. Sensitivity was reduced at the 500 ng/ml cutoff. Discrepancies between EtG and EtS were few. Comparison of self-reports of abstinence and EtG-confirmed abstinence indicated underreporting of drinking. CONCLUSIONS: Any drinking the night before should be detectable the following morning with EtG cutoffs of 100 or 200 ng/ml. Twenty-four hours after drinking, sensitivity is poor for light drinking, but good for heavier consumption. At 48 hours, sensitivity is low following 6 drinks or less. Increasing the cutoff to 500 ng/ml leads to substantially reduced sensitivity. Monitoring both EtG and EtS should usually be unnecessary. We recommend EtG-confirmed self-reports of abstinence for evaluation of outcomes in clinical trials.

A comprehensive, simulation-based approach to teaching clinical skills: the medical students' perspective.

The purpose of this study was to determine if third-year medical students participating in a mandatory 12-week simulation course perceived improvement in decision-making, communication, and teamwork skills. Students participated in or observed 24 acute emergency scenarios. At 4-week intervals, students completed 0-10 point Likert scale questionnaires evaluating the curriculum and role of team leader. Linear contrasts were used to examine changes in outcomes. P-values were Bonferroni-corrected for multiple pairwise comparisons. Student evaluations (n = 96) demonstrated increases from week 4 to 12 in educational value (p = 0.006), decision-making (p < 0.001), communication (p = 0.02), teamwork (p = 0.01), confidence in management (p < 0.001), and translation to clinical experience (p < 0.001). Regarding the team leader role, students reported a decrease in stress (p = 0.001) and increase in ability to facilitate team function (p < 0.001) and awareness of team building (p = <0.001). Ratings demonstrate a positive impact of simulation on both clinical management skills and team leadership skills. A simulation curriculum can enhance the ability to manage acute clinical problems and translates well to the clinical experience. These positive perceptions increase as the exposure to simulation increases.

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.

Strategies for dealing with missing data in clinical trials: from design to analysis.

Randomized clinical trials are the gold standard for evaluating interventions as randomized assignment equalizes known and unknown characteristics between intervention groups. However, when participants miss visits, the ability to conduct an intent-to-treat analysis and draw conclusions about a causal link is compromised. As guidance to those performing clinical trials, this review is a non-technical overview of the consequences of missing data and a prescription for its treatment beyond the typical analytic approaches to the entire research process. Examples of bias from incorrect analysis with missing data and discussion of the advantages/disadvantages of analytic methods are given. As no single analysis is definitive when missing data occurs, strategies for its prevention throughout the course of a trial are presented. We aim to convey an appreciation for how missing data influences results and an understanding of the need for careful consideration of missing data during the design, planning, conduct, and analytic stages.

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 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.

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.

CT overuse for mild traumatic brain injury.

BACKGROUND: Multiple, validated, evidence-based guidelines exist to inform the appropriate use of computed tomography (CT) to differentiate mild traumatic brain injury (MTBI) from clinically important brain injury and to prevent the overuse of CT. Yet, CT use is growing rapidly, potentially exposing patients to unnecessary ionizing radiation risk and costs. A study was conducted to quantify the overuse of CT in MTBI on the basis of current guideline recommendations. METHODS: A retrospective analysis of secondary data from a prospective observational study was undertaken at an urban, Level I emergency department (ED) with more than 90,000 visits per year. For adult patients with minor head injury receiving CT imaging at the discretion of the treating physician, the proportion of cases meeting criteria for CT on the basis of the Canadian CT Head Rule (CCHR), American College of Emergency Physicians (ACEP) Clinical Policy, New Orleans Criteria (NOC), and National Institute for Health and Clinical Excellence (NICE) guidelines was reported. RESULTS: All 346 patients enrolled in the original study were included in the analysis. The proportion of cases meeting criteria for CT for each of the guidelines was: CCHR 64.7% (95% confidence interval [CI], 0.60-0.70), ACEP 74.3% (95% CI, 0.70-0.79), NICE 86.7% (95% CI, 0.83-0.90), and NOC 90.5% (95% CI, 0.87-0.94). The odds ratio of the guidelines for predicting positive head CT findings were also reported. DISCUSSION: Some 10%-35% of CTs obtained in the ED for MTBI were not recommended according to the guidelines. Successful implementation of existing guidelines could decrease CT use in MTBI by up to 35%, leading to a significant reduction in radiation-induced cancers and health care costs.

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.

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.