Participant flow diagrams for health equity in AI.

Selection bias can arise through many aspects of a study, including recruitment, inclusion/exclusion criteria, input-level exclusion and outcome-level exclusion, and often reflects the underrepresentation of populations historically disadvantaged in medical research. The effects of selection bias can be further amplified when non-representative samples are used in artificial intelligence (AI) and machine learning (ML) applications to construct clinical algorithms. Building on the "Data Cards" initiative for transparency in AI research, we advocate for the addition of a participant flow diagram for AI studies detailing relevant sociodemographic and/or clinical characteristics of excluded participants across study phases, with the goal of identifying potential algorithmic biases before their clinical implementation. We include both a model for this flow diagram as well as a brief case study explaining how it could be implemented in practice. Through standardized reporting of participant flow diagrams, we aim to better identify potential inequities embedded in AI applications, facilitating more reliable and equitable clinical algorithms.

EMPOWER: A Multi-Site Pilot Trial to Reduce Distress in Surrogate Decision-Makers in the ICU.

CONTEXT: Efforts to reduce the psychological distress of surrogate decision-makers of critically ill patients have had limited success, and some have even exacerbated distress. OBJECTIVES: The aim of this study was to determine the feasibility, acceptability, and preliminary efficacy of EMPOWER (Enhancing and Mobilizing the POtential for Wellness and Resilience), an ultra-brief (∼2-hour), 6-module manualized psychological intervention for surrogates. METHODS: Surrogates who reported significant anxiety and/or an emotionally close relationship with the patient (n=60) were randomized to receive EMPOWER or enhanced usual care (EUC) at one of three metropolitan hospitals. Participants completed evaluations of EMPOWER's acceptability and measures of psychological distress pre-intervention, immediately post-intervention, and at 1- and 3-month follow-up assessments. RESULTS: Delivery of EMPOWER appeared feasible, with 89% of participants completing all 6 modules, and acceptable, with high ratings of satisfaction (mean=4.5/5, SD = .90). Compared to EUC, intent-to-treat analyses showed EMPOWER was superior at reducing peritraumatic distress (Cohen's d = -0.21, small effect) immediately post-intervention and grief intensity (d = -0.70, medium-large effect), posttraumatic stress (d = -0.74, medium-large effect), experiential avoidance (d = -0.46, medium effect), and depression (d = -0.34, small effect) 3 months post-intervention. Surrogate satisfaction with overall critical care (d = 0.27, small effect) was higher among surrogates randomized to EMPOWER. CONCLUSIONS: EMPOWER appeared feasible and acceptable, increased surrogates' satisfaction with critical care, and prevented escalation of posttraumatic stress, grief, and depression 3 months later.

Advance care planning (ACP) to promote receipt of value-concordant care: Results vary according to patient priorities.

BACKGROUND: Benefits of advance care planning (ACP) have recently been questioned by experts, but ACP is comprised of discrete activities. Little is known about which, if any, ACP activities are associated with patients' greater likelihood of receiving value-concordant end-of-life (EoL) care. OBJECTIVES: To determine which ACP activities [Do-Not-Resuscitate (DNR) order completion, designation of a healthcare proxy (HCP), and/or EoL discussions with physicians], individually and in combination, are associated with the greatest likelihood of receiving value-concordant care, and how results may vary based on patient-reported EoL care priorities. METHODS: Data from 2 federally-funded, multisite, prospective cohort studies of EoL cancer care from 2002-2019 were analyzed. Cancer patients (N = 278) with metastatic disease refractory to chemotherapy were interviewed for a baseline assessment and followed prospectively until death. Interviews regarding patient priorities occurred a median of 111 days prior to death; data regarding EoL medical care were collected post-mortem from caregiver interviews and medical record abstraction. Patients who 1) prioritized life-extending care, and then received life-extending care (or avoided hospice care), or 2) prioritized comfort-focused care, and then avoided life-extending care (or received hospice care) in the last week of life, were coded as receiving value-concordant care. RESULTS: After inverse propensity score weighting, the ACP combination associated with the largest proportion of patients receiving value-concordant care was DNR, HCP, and EoL discussions (87% vs. 64% for no ACP activities; OR = 3.91, p = 0.006). In weighted analyses examining each ACP activity individually, DNR orders were associated with decreased likelihood of life-extending care (89% vs. 75%; p = 0.005) and EoL discussions were associated with increased likelihood of hospice care (77% vs. 55%; p = 0.002) among patients prioritizing comfort. ACP activities were not significantly associated with increased likelihood of receiving value-concordant care among patients prioritizing life-extension. CONCLUSIONS AND RELEVANCE: For patients who prioritize comfort, EoL discussions with physicians and completion of DNR orders may improve odds of receiving value-concordant EoL care. For patients who prioritize life-extension, ACP does not appear to improve odds of receiving value-concordant EoL care.

Associations of financial hardship with suicidal ideation among bereaved cancer caregivers.

PURPOSE: To examine associations between financial hardship and suicidal ideation among bereaved informal caregivers of cancer patients. DESIGN: Longitudinal cohort study. SAMPLE: 173 informal caregivers of advanced cancer patients. METHODS: Caregivers were interviewed a median 3.1 months before and 6.5 months after the death of the patient they cared for. Logistic regression models estimated associations between caregiver-perceived pre-loss and post-loss financial hardship due to the patient's illness and post-loss suicidal ideation. FINDINGS: Suicidal ideation was identified in 12% (n = 21) of the sample pre-loss, rising to 20% (n = 34) post-loss (p=.049). Pre-loss financial hardship (OR = 3.4, 95% CI = 1.5-7.4, p=.002) and post-loss financial hardship (OR = 3.7, 95% CI = 1.7-8.2, p=.001) were each bivariately associated with post-loss suicidal ideation. In multivariable models adjusting for pre-loss suicidal ideation, psychiatric diagnosis, and spousal relationship to the patient, post-loss financial hardship remained significantly associated with post-loss suicidal ideation (AOR = 3.6, 95% CI = 1.4-8.8, p=.006). CONCLUSION: Among a cohort of cancer caregivers followed from active caregiving into bereavement, post-loss financial hardship was associated with suicidal ideation in bereavement. IMPLICATIONS: Economic policies that financially benefit caregivers may represent promising strategies for preventing suicidal thoughts and behaviors.

Associations of Intellectual Disability with Cardiopulmonary Resuscitation and Endotracheal Intubation at End of Life.

Background: Little is known about end-of-life intensive care provided to patients with intellectual disabilities (ID). Objectives: To identify differences in receipt of end-of-life cardiopulmonary resuscitation (CPR) and endotracheal intubation among adult patients with and without ID and examine whether do-not-resuscitate orders (DNRs) mediate associations between ID and CPR. Design: Exploratory matched cohort study using medical records of inpatient decedents treated between 2012 and 2018. Results: Patients with ID (n = 37) more frequently received CPR (37.8% vs. 21.6%) and intubation (78.4% vs. 47.8%) than patients without ID (n = 74). In multivariable models, ID was associated with receiving CPR (relative risk [RR] = 2.92, 95% confidence interval = 1.26-6.78, p = 0.012), but not intubation. Patients with ID less frequently had a DNR placed (67.6% vs. 91.9%), mediating associations between ID and CPR. Conclusions: In this pilot study, ID was associated with increased likelihood of receiving end-of-life CPR, likely due to lower utilization of DNRs among patients with ID. Further research is needed to confirm these results.

Development and preliminary evaluation of EMPOWER for surrogate decision-makers of critically ill patients.

OBJECTIVE: The objectives of this study were to develop and refine EMPOWER (Enhancing and Mobilizing the POtential for Wellness and Resilience), a brief manualized cognitive-behavioral, acceptance-based intervention for surrogate decision-makers of critically ill patients and to evaluate its preliminary feasibility, acceptability, and promise in improving surrogates' mental health and patient outcomes. METHOD: Part 1 involved obtaining qualitative stakeholder feedback from 5 bereaved surrogates and 10 critical care and mental health clinicians. Stakeholders were provided with the manual and prompted for feedback on its content, format, and language. Feedback was organized and incorporated into the manual, which was then re-circulated until consensus. In Part 2, surrogates of critically ill patients admitted to an intensive care unit (ICU) reporting moderate anxiety or close attachment were enrolled in an open trial of EMPOWER. Surrogates completed six, 15-20 min modules, totaling 1.5-2 h. Surrogates were administered measures of peritraumatic distress, experiential avoidance, prolonged grief, distress tolerance, anxiety, and depression at pre-intervention, post-intervention, and at 1-month and 3-month follow-up assessments. RESULTS: Part 1 resulted in changes to the EMPOWER manual, including reducing jargon, improving navigability, making EMPOWER applicable for a range of illness scenarios, rearranging the modules, and adding further instructions and psychoeducation. Part 2 findings suggested that EMPOWER is feasible, with 100% of participants completing all modules. The acceptability of EMPOWER appeared strong, with high ratings of effectiveness and helpfulness (M = 8/10). Results showed immediate post-intervention improvements in anxiety (d = -0.41), peritraumatic distress (d = -0.24), and experiential avoidance (d = -0.23). At the 3-month follow-up assessments, surrogates exhibited improvements in prolonged grief symptoms (d = -0.94), depression (d = -0.23), anxiety (d = -0.29), and experiential avoidance (d = -0.30). SIGNIFICANCE OF RESULTS: Preliminary data suggest that EMPOWER is feasible, acceptable, and associated with notable improvements in psychological symptoms among surrogates. Future research should examine EMPOWER with a larger sample in a randomized controlled trial.

Associations between beta-blocker use and psychological distress in bereaved adults with cardiovascular conditions.

The death of a close other is a major life stressor that disrupts mental and physical health. Beta-blocker medications are indicated treatments for cardiovascular conditions that may also mitigate psychological distress in the context of stressors by reducing adrenergic activity. We sought to examine observational links between beta-blocker medication use and psychological distress during bereavement. Using publicly available data from the Midlife in the United States Refresher study, we examined associations between beta-blocker use and general distress, depressive symptoms, and anxiety symptoms (as measured by the Mood and Anxiety Symptom Questionnaire) among bereaved adults with cardiovascular conditions (n = 161) using t-tests and regression models. Beta-blocker users reported lower levels of anxiety-related general distress (b = -2.49, SE = 0.88, p = 0.005) and depression-related general distress than non-users (b = -2.39, SE = 1.14, p = 0.039) in multivariate linear regression models adjusting for demographic characteristics, mental health treatments, time since loss and comorbid health conditions. These observed links between beta-blockers and lower psychological distress in bereavement warrant further investigation in prospective and randomized studies, as beta-blockers could be a scalable intervention for mitigating distress following loss.

Suffering and Symptoms At the End of Life in ICU Patients Undergoing Renal Replacement Therapy.

BACKGROUND: We know little about the end-of-life suffering and symptoms of intensive care unit (ICU) decedents in general and those who undergo renal replacement therapy (RRT) in particular. OBJECTIVES: To examine differences in end-of-life suffering and various symptoms' contribution to suffering between ICU decedents who did not undergo RRT, those who underwent RRT for end-stage kidney disease (ESKD), and those who underwent RRT for acute kidney injury (AKI). METHODS: This is a cross-sectional study conducted at a quaternary-level referral hospital September 2015-March 2017. Nurses completed interviews about ICU patients' suffering and symptoms in their final week. We dichotomized overall suffering into elevated and non-elevated and each symptom as contributing or not to a patient's suffering. RESULTS: Sixty-four nurses completed interviews on 165 patients. Median patient age was 67 years (interquartile range 57, 78); 41% were female. In a multivariable model, undergoing RRT for AKI (odds ratio [OR] 2.95, 95% confidence interval [CI] 1.34-6.49) was significantly associated with elevated suffering compared to no RRT; undergoing RRT for ESKD was not. Adjusting for length of stay, AKI-RRT patients were more likely than non-RRT patients to have fecal incontinence (OR 2.21, 95% CI 1.00-4.93), painful broken skin (OR 2.41, 95% CI 1.14-5.12), and rashes (OR 3.61, 95% CI 1.35-9.67) contributing to their suffering. CONCLUSIONS: Undergoing RRT for AKI was associated with elevated suffering in the last week of life in ICU decedents. Painful broken skin, rashes, and fecal incontinence were more likely to contribute to suffering in AKI-RRT patients than in non-RRT patients. How to reduce suffering associated with AKI-RRT in ICU patients merits further study.

Dementia and Early Do-Not-Resuscitate Orders Associated With Less Intensive of End-of-Life Care: A Retrospective Cohort Study.

BACKGROUND: Dementia is a leading cause of death among US older adults. Little is known about end-of-life care intensity and do-not-resuscitate orders (DNRs) among patients with dementia who die in hospital. AIM: Examine the relationship between dementia, DNR timing, and end-of-life care intensity. DESIGN: Observational cohort study. SETTING/PARTICIPANTS: Inpatient electronic health record extraction for 2,566 persons age 65 and older who died in 2 New York City hospitals in the United States from 2015 to 2017. RESULTS: Multivariable logistic regression analyses modeled associations between dementia diagnosis, DNR timing, and 6 end-of-life care outcomes. 31% of subjects had a dementia diagnosis; 23% had a DNR on day of hospital admission. Patients with dementia were 18%-40% less likely to have received 4 of 6 types of intensive care (mechanical ventilation AOR: 0.82, 95%CI: 0.67 -1.00; intensive care unit admission AOR: 0.60, 95%CI: 0.49-0.83). Having a DNR on file was inversely associated with staying in the intensive care unit (AOR: 0.57, 95%CI: 0.47-0.70) and avoiding other intensive care measures. DNR placement later during the hospitalization and not having a DNR were associated with more intensive care compared to having a DNR upon admission. CONCLUSIONS: Having dementia and a do-not resuscitate order upon hospital admission are associated with less intensive end-of-life care. Additional research is needed to understand why persons with dementia receive less intensive care. In clinical practice, encouraging advance care planning prior to and at hospital admission may be particularly important for patients wishing to avoid intensive end-of-life care, including patients with dementia.

Enhancing & Mobilizing the POtential for Wellness & Emotional Resilience (EMPOWER) among Surrogate Decision-Makers of ICU Patients: study protocol for a randomized controlled trial.

BACKGROUND: Critical illness increases the risk for poor mental health outcomes among both patients and their informal caregivers, especially their surrogate decision-makers. Surrogates who must make life-and-death medical decisions on behalf of incapacitated patients may experience additional distress. EMPOWER (Enhancing & Mobilizing the POtential for Wellness & Emotional Resilience) is a novel cognitive-behavioral, acceptance-based intervention delivered in the intensive care unit (ICU) setting to surrogate decision-makers designed to improve both patients' quality of life and death and dying as well as surrogates' mental health. METHODS: Clinician stakeholder and surrogate participant feedback (n = 15), as well as results from an open trial (n = 10), will be used to refine the intervention, which will then be evaluated through a multisite randomized controlled trial (RCT) (n = 60) to examine clinical superiority to usual care. Feasibility, tolerability, and acceptability of the intervention will be evaluated through self-report assessments. Hierarchical linear modeling will be used to adjust for clustering within interventionists to determine the effect of EMPOWER on surrogate differences in the primary outcome, peritraumatic stress. Secondary outcomes will include symptoms of post-traumatic stress disorder, prolonged grief disorder, and experiential avoidance. Exploratory outcomes will include symptoms of anxiety, depression, and decision regret, all measured at 1 and 3 months from post-intervention assessment. Linear regression models will examine the effects of assignment to EMPOWER versus the enhanced usual care group on patient quality of life or quality of death and intensity of care the patient received during the indexed ICU stay assessed at the time of the post-intervention assessment. Participant exit interviews will be conducted at the 3-month assessment time point and will be analyzed using qualitative thematic data analysis methods. DISCUSSION: The EMPOWER study is unique in its application of evidence-based psychotherapy targeting peritraumatic stress to improve patient and caregiver outcomes in the setting of critical illness. The experimental intervention will be strengthened through the input of a variety of ICU stakeholders, including behavioral health clinicians, physicians, bereaved informal caregivers, and open trial participants. Results of the RCT will be submitted for publication in a peer-reviewed journal and serve as preliminary data for a larger, multisite RCT grant application. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03276559 . Retrospectively registered on 8 September 2017.

Suicidal Ideation in Bereavement: A Systematic Review.

Background: Bereavement is associated with impaired mental health, increases in adverse health behaviors, and heightened risk of suicidal ideation, attempts, and death by suicide. The purpose of this literature review was to explore associations between cause of death and suicidal thoughts among bereaved individuals. Our aim was to compare incidence of suicidal ideation by cause of death and identify gaps in this literature to guide future research and clinical intervention. Methods: PRISMA-P guidelines were used to structure an electronic literature search in the PsycINFO, MEDLINE, and Web of Science databases. The search focused on English language studies that were published before February 2019 and sought to compare rates of suicidal ideation among bereaved people who lost a loved one to suicide, accidental overdose, cancer, dementia, cardiovascular disease, and HIV/AIDs. Results: Ten articles were identified with suicide as cause of death, zero articles for accidental overdose, zero articles for cardiovascular disease, eight articles for cancer, one article for dementia, and one article for HIV/AIDs. Given the limited number of articles generated by our search, a formal meta-analysis was not appropriate. However, a comparison of results did suggest that suicide bereavement was associated with the highest rates of suicide ideation (14.1% to 49%). Stigma, isolation, avoidance behaviors, and psychological distress were associated with suicidal thoughts among bereaved individuals, regardless of the deceased's cause of death. Conclusions: Findings of this literature search revealed significant gaps in the literature, especially regarding thoughts of suicide in bereaved survivors of accidental overdose and cardiovascular disease. Results suggest that multiple causes of death are associated with suicidal ideation in bereavement, but that suicide bereavement may be the cause of death associated with the highest risk of suicidal ideation. More research is needed to understand the ways in which cause of death influences prevalence, risk, and protective factors associated with suicidal thoughts among bereaved individuals.

Telomere length study in celiac disease.

OBJECTIVES: Telomeres are important structures that are critical for maintaining chromosomal integrity and cell surveillance. The aim of this study was to analyze telomere length in patients with celiac disease (CD), a multifactorial disorder with a strong genetic component that exhibits genomic instability and cancer predisposition, particularly T-cell lymphomas. METHODS: Telomere length measured by telomere restriction fragments (TRF) was studied in small intestinal biopsy (SIB) samples and peripheral blood lymphocytes (PBL) from 20 untreated CD patients, distributed according to the clinical form as four asymptomatic, five monosymptomatic, and 11 polysymptomatic individuals. We also analyzed TRF from normal peripheral blood lymphocytes and normal biopsy samples as normal controls. RESULTS: TRF evaluation showed a significant telomere shortening in SIB samples from CD patients (4.21 +/- 0.29 Kb) compared to PBL from the same individuals (9.17 +/- 0.35 Kb) (p < 0.0001), independently of clinical form. Mean TRF peak values from normal biopsy samples were significantly higher (8.33 +/- 0.38 Kb) than those observed in CD biopsy samples (p < 0.001). No differences between TRF values in CD-PBL and normal peripheral blood lymphocytes (8.89 +/- 0.37Kb) were found. CONCLUSIONS: Our findings in patients with CD, a disorder in which the gluten-induced mucosal injury could accelerate telomere shortening, would increase the process of end-to-end fusions resulting in chromosomal changes, supports the hypothesis that genomic instability and telomere reduction may play a role in the cancer predisposition observed in these patients.

Value of a screening algorithm for celiac disease using tissue transglutaminase antibodies as first level in a population-based study.

OBJECTIVE: Serological screening for celiac disease (CD) can detect a large number of otherwise undiagnosed patients based on the sequential evaluation of serological tests and intestinal biopsy. The aim of this study was to compare the screening value for CD of two different protocols for the same community-based population. METHODS: We screened 1,000 consecutive subjects (497 women, age range 16-71 yr) attending a centralized laboratory for obligatory prenuptial blood tests. Serum samples obtained from all subjects were processed using two different protocols: I) a three-level classic screening consisting of the parallel use of IgG and IgA antigliadin antibodies as first level, followed by endomysial antibodies and total serum IgA for positive patients, and finally, intestinal biopsy of positive patients; and 2) a study screening protocol consisting of the parallel use of a commercial guinea pig antitissue transglutaminase antibody and total serum IgA as first line, endomysial antibodies (type IgA and/or IgG) for positive patients, and finally, intestinal biopsy. RESULTS: The classic screening protocol identified five subjects who were eligible for intestinal biopsy, which confirmed the presence of CD in all (prevalence 5.0 x 1,000, 95% CI = 1.6-11.6). Using the study algorithm, we detected seven new patients including the five patients detected by the first protocol (prevalence 7.0 x 1,000, 95% CI = 2.8-14.4). The two additional patients diagnosed using the proposed algorithm had positive IgG antigliadin antibodies and normal total serum IgA and were not detected by the classic protocol. Both patients were endomysial antibodies positive. The comparative analysis showed that the classic approach was more expensive (U.S. $4,687 per new patient detected) compared with the proposed study algorithm (U.S. $3,006). CONCLUSIONS: Our data showed that a new screening protocol using antitissue transglutaminase as first line followed by endomysial antibodies is a cost-effective screening and yielded more realistic figures of prevalence for CD in a community setting than the classic three-level sequential evaluation using antigliadin antibodies.