Emergency Medicine Palliative Care Access (EMPallA): Protocol for a multicentre randomised controlled trial comparing the effectiveness of specialty outpatient versus nurse-led telephonic palliative care of older adults with advanced illness

Introduction Emergency department (ED)-initiated palliative care has been shown to improve patient-centred outcomes in older adults with serious, life-limiting illnesses. However, the optimal modality for providing such interventions is unknown. This study aims to compare nurse-led telephonic case management to specialty outpatient palliative care for older adults with serious, life-limiting illness on: (1) quality of life in patients; (2) healthcare utilisation; (3) loneliness and symptom burden and (4) caregiver strain, caregiver quality of life and bereavement. Methods and analysis This is a protocol for a pragmatic, multicentre, parallel, two-arm randomised controlled trial in ED patients comparing two established models of palliative care: nurse-led telephonic case management and specialty, outpatient palliative care. We will enrol 1350 patients aged 50+ years and 675 of their caregivers across nine EDs. Eligible patients: (1) have advanced cancer (metastatic solid tumour) or end-stage organ failure (New York Heart Association class III or IV heart failure, end-stage renal disease with glomerular filtration rate /min/m2, or global initiative for chronic obstructive lung disease stage III, IV or oxygen-dependent chronic obstructive pulmonary disease); (2) speak English; (3) are scheduled for ED discharge or observation status; (4) reside locally; (5) have a working telephone and (6) are insured. Patients will be excluded if they: (1) have dementia; (2) have received hospice care or two or more palliative care visits in the last 6 months or (3) reside in a long-term care facility. We will use patient-level block randomisation, stratified by ED site and disease. Effectiveness will be compared by measuring the impact of each intervention on the specified outcomes. The primary outcome will measure change in patient quality of life. Ethics and dissemination Institutional Review Board approval was obtained at all study sites. Trial results will be submitted for publication in a peer-reviewed journal

Accelerometer and GPS Data to Analyze Built Environments and Physical Activity

Purpose: Most built environment studies have quantified characteristics of the areas around participants' homes. However, the environmental exposures for physical activity (PA) are spatially dynamic rather than static. Thus, merged accelerometer and global positioning system (GPS) data were utilized to estimate associations between the built environment and PA among adults. Methods: Participants (N = 142) were recruited on trails in Massachusetts and wore an accelerometer and GPS unit for 1-4 days. Two binary outcomes were created: moderate-to-vigorous PA (MVPA vs. light PA-to-sedentary); and light-to-vigorous PA (LVPA vs. sedentary). Five built environment variables were created within 50-meter buffers around GPS points: population density, street density, land use mix (LUM), greenness, and walkability index. Generalized linear mixed models were fit to examine associations between environmental variables and both outcomes, adjusting for demographic covariates. Results: Overall, in the fully adjusted models, greenness was positively associated with MVPA and LVPA (odds ratios [ORs] = 1.15, 95% confidence interval [CI] = 1.03, 1.30 and 1.25, 95% CI = 1.12, 1.41, respectively). In contrast, street density and LUM were negatively associated with MVPA (ORs = 0.69, 95% CI = 0.67, 0.71 and 0.87, 95% CI = 0.78, 0.97, respectively) and LVPA (ORs = 0.79, 95% CI = 0.77, 0.81 and 0.81, 95% CI = 0.74, 0.90, respectively). Negative associations of population density and walkability with both outcomes reached statistical significance, yet the effect sizes were small. Conclusions: Concurrent monitoring of activity with accelerometers and GPS units allowed us to investigate relationships between objectively measured built environment around GPS points and minute-by-minute PA. Negative relationships between street density and LUM and PA contrast evidence from most built environment studies in adults. However, direct comparisons should be made with caution since most previous studies have focused on spatially fixed buffers around home locations, rather than the precise locations where PA occurs

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial

Importance: There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective: To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, setting, and participants: CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions: A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main outcomes and measures: The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results: Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR Conclusions and relevance: In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. Trial registration: ClinicalTrials.gov Identifier: NCT04364737

COVID-19 Convalescent Plasma Therapy: Long-term Implications

BACKGROUND: The long-term effect of coronavirus disease 2019 (COVID-19) acute treatments on postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is unknown. The CONTAIN-Extend study explores the long-term impact of COVID-19 convalescent plasma (CCP) therapy on postacute sequelae of SARS-CoV-2 infection (PASC) symptoms and general health 18 months following hospitalization. METHODS: The CONTAIN-Extend study examined 281 participants from the original CONTAIN COVID-19 trial (CONTAIN-RCT, NCT04364737) at 18 months post-hospitalization for acute COVID-19. Symptom surveys, global health assessments, and biospecimen collection were performed from November 2021 to October 2022. Multivariable logistic and linear regression estimated associations between the randomization arms and self-reported symptoms and Patient-Reported Outcomes Measurement Information System (PROMIS) scores and adjusted for covariables, including age, sex, race/ethnicity, disease severity, and CONTAIN enrollment quarter and sites. RESULTS: There were no differences in symptoms or PROMIS scores between CCP and placebo (adjusted odds ratio [aOR] of general symptoms, 0.95; 95% CI, 0.54-1.67). However, females (aOR, 3.01; 95% CI, 1.73-5.34), those 45-64 years (aOR, 2.55; 95% CI, 1.14-6.23), and April-June 2020 enrollees (aOR, 2.39; 95% CI, 1.10-5.19) were more likely to report general symptoms and have poorer PROMIS physical health scores than their respective reference groups. Hispanic participants (difference, -3.05; 95% CI, -5.82 to -0.27) and Black participants (-4.48; 95% CI, -7.94 to -1.02) had poorer PROMIS physical health than White participants. CONCLUSIONS: CCP demonstrated no lasting effect on PASC symptoms or overall health in comparison to the placebo. This study underscores the significance of demographic factors, including sex, age, and timing of acute infection, in influencing symptom reporting 18 months after acute hypoxic COVID-19 hospitalization

Long-Term Relationships between Synaptic Tenacity, Synaptic Remodeling, and Network Activity

Long term time-lapse imaging reveals that individual synapses undergo significant structural remodeling not only when driven by activity, but also when network activity is absent, raising questions about how reliably individual synapses maintain connections

Data from emergency medicine palliative care access (EMPallA): a randomized controlled trial comparing the effectiveness of specialty outpatient versus telephonic palliative care of older adults with advanced illness presenting to the emergency department.

BACKGROUND: The Emergency Medicine Palliative Care Access (EMPallA) trial is a large, multicenter, parallel, two-arm randomized controlled trial in emergency department (ED) patients comparing two models of palliative care: nurse-led telephonic case management and specialty, outpatient palliative care. This report aims to: 1) report baseline demographic and quality of life (QOL) data for the EMPallA cohort, 2) identify the association between illness type and baseline QOL while controlling for other factors, and 3) explore baseline relationships between illness type, symptom burden, and loneliness. METHODS: Patients aged 50+ years with advanced cancer (metastatic solid tumor) or end-stage organ failure (New York Heart Association Class III or IV heart failure, end stage renal disease with glomerular filtration rate \u3c 15 mL/min/m2, or Global Initiative for Chronic Obstructive Lung Disease Stage III, IV, or oxygen-dependent chronic obstructive pulmonary disease defined as FEV1 \u3c 50%) are eligible for enrollment. Baseline data includes self-reported demographics, QOL measured by the Functional Assessment of Cancer Therapy-General (FACT-G), loneliness measured by the Three-Item UCLA Loneliness Scale, and symptom burden measured by the Edmonton Revised Symptom Assessment Scale. Descriptive statistics were used to analyze demographic variables, a linear regression model measured the importance of illness type in predicting QOL, and chi-square tests of independence were used to quantify relationships between illness type, symptom burden, and loneliness. RESULTS: Between April 2018 and April 3, 2020, 500 patients were enrolled. On average, end-stage organ failure patients had lower QOL as measured by the FACT-G scale than cancer patients with an estimated difference of 9.6 points (95% CI: 5.9, 13.3), and patients with multiple conditions had a further reduction of 7.4 points (95% CI: 2.4, 12.5), when adjusting for age, education level, race, sex, immigrant status, presence of a caregiver, and hospital setting. Symptom burden and loneliness were greater in end-stage organ failure than in cancer. CONCLUSIONS: The EMPallA trial is enrolling a diverse sample of ED patients. Differences by illness type in QOL, symptom burden, and loneliness demonstrate how distinct disease trajectories manifest in the ED. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03325985 . Registered October 30, 2017

Taking the Analysis of Trial-Based Economic Evaluations to the Next Level:The Importance of Accounting for Clustering

OBJECTIVES: The aim of this study was to assess the performance and impact of multilevel modelling (MLM) compared with ordinary least squares (OLS) regression in trial-based economic evaluations with clustered data. METHODS: Three thousand datasets with balanced and unbalanced clusters were simulated with correlation coefficients between costs and effects of - 0.5, 0, and 0.5, and intraclass correlation coefficients (ICCs) varying between 0.05 and 0.30. Each scenario was analyzed using both MLM and OLS. Statistical uncertainty around MLM and OLS estimates was estimated using bootstrapping. Performance measures were estimated and compared between approaches, including bias, root mean squared error (RMSE) and coverage probability. Cost and effect differences, and their corresponding confidence intervals and standard errors, incremental cost-effectiveness ratios, incremental net-monetary benefits and cost-effectiveness acceptability curves were compared. RESULTS: Cost-effectiveness outcomes were similar between OLS and MLM. MLM produced larger statistical uncertainty and coverage probabilities closer to nominal levels than OLS. The higher the ICC, the larger the effect on statistical uncertainty between MLM and OLS. Significant cost-effectiveness outcomes as estimated by OLS became non-significant when estimated by MLM. At all ICCs, MLM resulted in lower probabilities of cost effectiveness than OLS, and this difference became larger with increasing ICCs. Performance measures and cost-effectiveness outcomes were similar across scenarios with varying correlation coefficients between costs and effects. CONCLUSIONS: Although OLS produced similar cost-effectiveness outcomes, it substantially underestimated the amount of variation in the data compared with MLM. To prevent suboptimal conclusions and a possible waste of scarce resources, it is important to use MLM in trial-based economic evaluations when data are clustered