Faculty Bibliography

IMPORTANCE/UNASSIGNED:The emergency department (ED) offers an opportunity to initiate palliative care for older adults with serious, life-limiting illness. OBJECTIVE/UNASSIGNED:To assess the effect of a multicomponent intervention to initiate palliative care in the ED on hospital admission, subsequent health care use, and survival in older adults with serious, life-limiting illness. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Cluster randomized, stepped-wedge, clinical trial including patients aged 66 years or older who visited 1 of 29 EDs across the US between May 1, 2018, and December 31, 2022, had 12 months of prior Medicare enrollment, and a Gagne comorbidity score greater than 6, representing a risk of short-term mortality greater than 30%. Nursing home patients were excluded. INTERVENTION/UNASSIGNED:A multicomponent intervention (the Primary Palliative Care for Emergency Medicine intervention) included (1) evidence-based multidisciplinary education; (2) simulation-based workshops on serious illness communication; (3) clinical decision support; and (4) audit and feedback for ED clinical staff. MAIN OUTCOME AND MEASURES/UNASSIGNED:The primary outcome was hospital admission. The secondary outcomes included subsequent health care use and survival at 6 months. RESULTS/UNASSIGNED:There were 98 922 initial ED visits during the study period (median age, 77 years [IQR, 71-84 years]; 50% were female; 13% were Black and 78% were White; and the median Gagne comorbidity score was 8 [IQR, 7-10]). The rate of hospital admission was 64.4% during the preintervention period vs 61.3% during the postintervention period (absolute difference, -3.1% [95% CI, -3.7% to -2.5%]; adjusted odds ratio [OR], 1.03 [95% CI, 0.93 to 1.14]). There was no difference in the secondary outcomes before vs after the intervention. The rate of admission to an intensive care unit was 7.8% during the preintervention period vs 6.7% during the postintervention period (adjusted OR, 0.98 [95% CI, 0.83 to 1.15]). The rate of at least 1 revisit to the ED was 34.2% during the preintervention period vs 32.2% during the postintervention period (adjusted OR, 1.00 [95% CI, 0.91 to 1.09]). The rate of hospice use was 17.7% during the preintervention period vs 17.2% during the postintervention period (adjusted OR, 1.04 [95% CI, 0.93 to 1.16]). The rate of home health use was 42.0% during the preintervention period vs 38.1% during the postintervention period (adjusted OR, 1.01 [95% CI, 0.92 to 1.10]). The rate of at least 1 hospital readmission was 41.0% during the preintervention period vs 36.6% during the postintervention period (adjusted OR, 1.01 [95% CI, 0.92 to 1.10]). The rate of death was 28.1% during the preintervention period vs 28.7% during the postintervention period (adjusted OR, 1.07 [95% CI, 0.98 to 1.18]). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This multicomponent intervention to initiate palliative care in the ED did not have an effect on hospital admission, subsequent health care use, or short-term mortality in older adults with serious, life-limiting illness. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03424109.

OBJECTIVE/UNASSIGNED:To compare the effectiveness of nurse led telephonic palliative care versus specialty outpatient palliative care on quality of life, symptom burden, loneliness, and healthcare use, after attending the emergency department. DESIGN/UNASSIGNED:Pragmatic, randomised clinical trial. SETTING/UNASSIGNED:Emergency Medicine Palliative Care Access (EMPallA) randomised controlled trial enrolling participants from 18 emergency departments in 15 geographically diverse healthcare systems in nine US states, from 1 April 2018 to 30 June 2022. PARTICIPANTS/UNASSIGNED:Of 39 254 eligible patients, 1283 adults who visited the emergency department, were aged ≥50 years, who spoke English or Spanish, and had advanced cancer or end stage organ failure, were randomised to receive nurse led telephonic palliative care (n=639) or specialty outpatient palliative care (n=644). INTERVENTIONS/UNASSIGNED:The nurse led telephonic palliative care arm consisted of weekly or biweekly calls over six months made by registered nurses certified in hospice and palliative care. For the specialty outpatient palliative care arm, patients had one visit each month for six months with a specialty trained hospice and palliative medicine provider. MAIN OUTCOME MEASURES/UNASSIGNED:The primary outcome was change in patient reported quality of life at six months, measured by the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. Secondary outcomes were change in symptom burden and patient reported loneliness after six months, and healthcare use, measured as the number of emergency department revisits, inpatient days, and hospice use, from enrolment to 12 months. RESULTS/UNASSIGNED:639 patients were assigned to nurse telephonic services and 434 (68%) engaged in care until death, or until they required hospice services or graduated from the programme. For specialty outpatient palliative care, 644 patients were assigned and 344 (53%) attended one or more visits, with an average of 2.7 visits. The mean change in FACT-G scores over six months for the nurse telephonic arm (n=418) was 3.7 (95% confidence interval (CI) 2.3 to 5.1) points compared with 3.1 (1.6 to 4.6) for those in the specialty outpatient care arm (n=409). In the model including all patients who survived to six months (n=1090), the estimated difference in average change in quality of life was 0.71 (95% CI -1.19 to 2.61) points higher in the nurse led telephonic palliative care arm. The analysis did not show any clinically meaningful differences in the change in quality of life between the treatment arms. Also, no important differences between groups were found for secondary outcomes or in subgroup analyses. CONCLUSIONS/UNASSIGNED:The results of the study provided no clear evidence that nurse led telephonic palliative care improved quality of life, or any secondary outcomes, relative to specialty outpatient palliative care. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov NCT03325985.

BACKGROUND:The optimal management of patients with intermediate-risk pulmonary embolism (PE), who have right heart dysfunction (determined by a combination of imaging and cardiac biomarkers) but a normal blood pressure, is uncertain. These patients suffer from reduced functional capacity and a lower quality of life over the long-term, despite use of anticoagulant therapy. Catheter-directed therapy (CDT) is a promising treatment for acute PE that rapidly removes thrombus and potentially improves cardiac dysfunction. However, CDT has risk and is costly, and it is not known whether it improves long-term cardiorespiratory fitness and/or quality of life compared with anticoagulation alone. METHODS:) with cardiopulmonary exercise testing at 3 months and reduce New York Heart Association (NYHA) Class at 12 months compared with No-CDT. These 2 primary efficacy outcomes will be analyzed sequentially using a "gatekeeping" procedure; for NYHA class to be compared, peak oxygen consumption must first be shown to be significantly increased by CDT. Safety and cost-effectiveness will also be assessed. CONCLUSION/CONCLUSIONS:When completed, PE-TRACT will provide important evidence regarding the benefits and risks of CDT to treat intermediate-risk PE compared with anticoagulation alone. TRIAL REGISTRATION/BACKGROUND:clinicaltrials.gov: NCT05591118.

CONTEXT/BACKGROUND:Outpatient Palliative Care (OPC) benefits persons living with serious illness, yet barriers exist in utilization. OBJECTIVES/OBJECTIVE:To identify factors associated with OPC clinic utilization. METHODS:Emergency Medicine Palliative Care Access is a multicenter, randomized control trial comparing two models of palliative care for patients recruited from the Emergency Department (ED): nurse-led telephonic case management and OPC (one visit a month for 6 months). Patients were aged 50+ with advanced cancer or end-stage organ failure and recruited from 19 EDs. Using a mixed effects hurdle model, we analyzed patient, provider, clinic and healthcare system factors associated with OPC utilization. RESULTS:Among the 603 patients randomized to OPC, about half (53.6%) of patients attended at least one clinic visit. Those with less than high school education were less likely to attend an initial visit than those with a college degree or higher (aOR 0.44; CI 0.23, 0.85), as were patients who required considerable assistance (aOR 0.45; CI 0.25, 0.82) or had congestive heart failure only (aOR 0.46; CI 0.26, 0.81). Those with higher symptom burden had a higher attendance at the initial visit (aOR 1.05; CI 1.00, 1.10). Reduced follow up visit rates were demonstrated for those of older age (aRR 0.90; CI 0.82, 0.98), female sex (aRR 0.84; CI 0.71, 0.99), and those that were never married (aRR 0.62; CI 0.52, 0.87). CONCLUSION/CONCLUSIONS:Efforts to improve OPC utilization should focus on those with lower education, more functional limitations, older age, female sex, and those with less social support. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER/UNASSIGNED:NCT03325985.

BACKGROUND:Precision medicine has led to the development of targeted treatment strategies tailored to individual patients based on their characteristics and disease manifestations. Although precision medicine often focuses on a single health outcome for individualized treatment decision rules (ITRs), relying only on a single outcome rather than all available outcomes information leads to suboptimal data usage when developing optimal ITRs. METHODS:To address this limitation, we propose a Bayesian multivariate hierarchical model that leverages the wealth of correlated health outcomes collected in clinical trials. The approach jointly models mixed types of correlated outcomes, facilitating the "borrowing of information" across the multivariate outcomes, and results in a more accurate estimation of heterogeneous treatment effects compared to using single regression models for each outcome. We develop a treatment benefit index, which quantifies the relative benefit of the experimental treatment over the control treatment, based on the proposed multivariate outcome model. RESULTS:We demonstrate the strengths of the proposed approach through extensive simulations and an application to an international Coronavirus Disease 2019 (COVID-19) treatment trial. Simulation results indicate that the proposed method reduces the occurrence of erroneous treatment decisions compared to a single regression model for a single health outcome. Additionally, the sensitivity analyses demonstrate the robustness of the model across various study scenarios. Application of the method to the COVID-19 trial exhibits improvements in estimating the individual-level treatment efficacy (indicated by narrower credible intervals for odds ratios) and optimal ITRs. CONCLUSION/CONCLUSIONS:The study jointly models mixed types of outcomes in the context of developing ITRs. By considering multiple health outcomes, the proposed approach can advance the development of more effective and reliable personalized treatment.

BACKGROUND:Offering medications for opioid use disorder (MOUD) in carceral settings significantly reduces overdose. However, it is unknown to what extent individuals in jails continue MOUD once they leave incarceration. We aimed to assess the relationship between in-jail MOUD and MOUD continuity in the month following release. METHODS:We conducted a retrospective cohort study of linked NYC jail-based electronic health records and community Medicaid OUD treatment claims for individuals with OUD discharged from jail between 2011 and 2017. We compared receipt of MOUD within 30 days of release, among those with and without MOUD at release from jail. We tested for effect modification based on MOUD receipt prior to incarceration and assessed factors associated with treatment discontinuation. RESULTS:Of 28,298 eligible incarcerations, 52.8 % received MOUD at release. 30 % of incarcerations with MOUD at release received community-based MOUD within 30 days, compared to 7 % of incarcerations without MOUD (Risk Ratio: 2.62 (2.44-2.82)). Most (69 %) with MOUD claims prior to incarceration who received in-jail MOUD continued treatment in the community, compared to 9 % of those without prior MOUD. Those who received methadone (vs. buprenorphine), were younger, Non-Hispanic Black and with no history of MOUD were less likely to continue MOUD following release. CONCLUSIONS:MOUD maintenance in jail is strongly associated with MOUD continuity upon release. Still, findings highlight a gap in treatment continuity upon-reentry, especially among those who initiate MOUD in jail. In the wake of worsening overdose deaths and troubling disparities, improving MOUD continuity among this population remains an urgent priority.

The cluster randomized crossover design has been proposed to improve efficiency over the traditional parallel-arm cluster randomized design. While statistical methods have been developed for designing cluster randomized crossover trials, they have exclusively focused on testing the overall average treatment effect, with little attention to differential treatment effects across subpopulations. Recently, interest has grown in understanding whether treatment effects may vary across pre-specified patient subpopulations, such as those defined by demographic or clinical characteristics. In this article, we consider the two-treatment two-period cluster randomized crossover design under either a cross-sectional or closed-cohort sampling scheme, where it is of interest to detect the heterogeneity of treatment effect via an interaction test. Assuming a patterned correlation structure for both the covariate and the outcome, we derive new sample size formulas for testing the heterogeneity of treatment effect with continuous outcomes based on linear mixed models. Our formulas also address unequal cluster sizes and therefore allow us to analytically assess the impact of unequal cluster sizes on the power of the interaction test in cluster randomized crossover designs. We conduct simulations to confirm the accuracy of the proposed methods, and illustrate their application in two real cluster randomized crossover trials.

Cluster-randomized trials (CRTs) often allocate intact clusters of participants to treatment or control conditions and are increasingly used to evaluate healthcare delivery interventions. While previous studies have developed sample size methods for testing confirmatory hypotheses of treatment effect heterogeneity in CRTs (i.e., targeting the difference between subgroup-specific treatment effects), sample size methods for testing the subgroup-specific treatment effects themselves have not received adequate attention-despite a rising interest in health equity considerations in CRTs. In this article, we develop formal methods for sample size and power analyses for testing subgroup-specific treatment effects in parallel-arm CRTs with a continuous outcome and a binary subgroup variable. We point out that the variances of the subgroup-specific treatment effect estimators and their covariance are given by weighted averages of the variance of the overall average treatment effect estimator and the variance of the heterogeneous treatment effect estimator. This analytical insight facilitates an explicit characterization of the requirements for both the omnibus test and the intersection-union test to achieve the desired level of power. Generalizations to allow for subgroup-specific variance structures are also discussed. We report on a simulation study to validate the proposed sample size methods and demonstrate that the empirical power corresponds well with the predicted power for both tests. The design and setting of the Umea Dementia and Exercise (UMDEX) CRT in older adults are used to illustrate our sample size methods.

BACKGROUND:Non-fatal overdose is a leading predictor of subsequent fatal overdose. For individuals who are incarcerated, the risk of experiencing an overdose is highest when transitioning from a correctional setting to the community. We assessed if enrollment in jail-based medications for opioid use disorder (MOUD) is associated with lower risk of non-fatal opioid overdoses after jail release among individuals with opioid use disorder (OUD). METHODS:This was a retrospective, observational cohort study of adults with OUD who were incarcerated in New York City jails and received MOUD or did not receive any MOUD (out-of-treatment) within the last three days before release to the community in 2011-2017. The outcome was the first non-fatal opioid overdose emergency department (ED) visit within 1 year of jail release during 2011-2017. Covariates included demographic, clinical, incarceration-related, and other characteristics. We performed multivariable cause-specific Cox proportional hazards regression analysis to compare the risk of non-fatal opioid overdose ED visits within 1 year after jail release between groups. RESULTS:MOUD group included 8660 individuals with 17,119 incarcerations; out-of-treatment group included 10,163 individuals with 14,263 incarcerations. Controlling for covariates and accounting for competing risks, in-jail MOUD was associated with lower non-fatal opioid overdose risk within 14 days after jail release (adjusted HR=0.49, 95% confidence interval=0.33-0.74). We found no significant differences 15-28, 29-56, or 57-365 days post-release. CONCLUSION/CONCLUSIONS:MOUD group had lower risk of non-fatal opioid overdose immediately after jail release. Wider implementation of MOUD in US jails could potentially reduce post-release overdoses, ED utilization, and associated healthcare costs.