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We investigated the risks of post-acute and chronic adverse kidney outcomes of SARS-CoV-2 infection in the pediatric population via a retrospective cohort study using data from the RECOVER program. We included 1,864,637 children and adolescents under 21 from 19 children's hospitals and health institutions in the US with at least six months of follow-up time between March 2020 and May 2023. We divided the patients into three strata: patients with pre-existing chronic kidney disease (CKD), patients with acute kidney injury (AKI) during the acute phase (within 28 days) of SARS-CoV-2 infection, and patients without pre-existing CKD or AKI. We defined a set of adverse kidney outcomes for each stratum and examined the outcomes within the post-acute and chronic phases after SARS-CoV-2 infection. In each stratum, compared with the non-infected group, patients with COVID-19 had a higher risk of adverse kidney outcomes. For patients without pre-existing CKD, there were increased risks of CKD stage 2+ (HR 1.20; 95% CI: 1.13-1.28) and CKD stage 3+ (HR 1.35; 95% CI: 1.15-1.59) during the post-acute phase (28 days to 365 days) after SARS-CoV-2 infection. Within the post-acute phase of SARS-CoV-2 infection, children and adolescents with pre-existing CKD and those who experienced AKI were at increased risk of progression to a composite outcome defined by at least 50% decline in estimated glomerular filtration rate (eGFR), eGFR <15 mL/min/1.73m2, End Stage Kidney Disease diagnosis, dialysis, or transplant.
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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 (â¼2-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.
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Unidades de Terapia Intensiva , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Projetos Piloto , Estudos de Viabilidade , Angústia Psicológica , Tomada de Decisões , Estado Terminal/psicologia , Adulto , Resultado do Tratamento , Idoso , Procurador/psicologia , Estresse Psicológico/terapia , Estresse Psicológico/psicologia , SeguimentosRESUMO
As of 2019, there are 4.2 million Filipino Americans (FAs) and 1.9 million Korean Americans (KAs) in the United States, largely concentrated in New York, California, Texas, Illinois, and Washington. In both populations, similar to the broader U.S. culture, one can find health literacy gaps around understanding and utilizing palliative care. In this article, we provide 10 cultural pearls to guide clinicians on how to sensitively approach FA and KA groups when addressing palliative and end-of-life (EOL) discussions. We fully celebrate that every person is an individual and care should be tailored to each person's goals, values, and preference. In addition, there are several cultural norms that, when appreciated and celebrated, may help clinicians to improve serious illness care and EOL discussions for members of these populations.
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Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Assistência Terminal , Humanos , Estados Unidos , Cuidados Paliativos , Asiático , Illinois , New YorkRESUMO
Rationale & Objective: PRESERVE seeks to provide new knowledge to inform shared decision-making regarding blood pressure (BP) management for pediatric chronic kidney disease (CKD). PRESERVE will compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; expand the National Patient-Centered Clinical Research Network (PCORnet) common data model by adding pediatric- and kidney-specific variables and linking electronic health record data to other kidney disease databases; and assess the lived experiences of patients related to BP management. Study Design: Multicenter retrospective cohort study (clinical outcomes) and cross-sectional study (patient-reported outcomes [PROs]). Setting & Participants: PRESERVE will include approximately 20,000 children between January 2009-December 2022 with mild-moderate CKD from 15 health care institutions that participate in 6 PCORnet Clinical Research Networks (PEDSnet, STAR, GPC, PaTH, CAPRiCORN, and OneFlorida+). The inclusion criteria were ≥1 nephrologist visit and ≥2 estimated glomerular filtration rate (eGFR) values in the range of 30 to <90 mL/min/1.73 m2 separated by ≥90 days without an intervening value ≥90 mL/min/1.73 m2 and no prior dialysis or kidney transplant. Exposures: BP measurements (clinic-based and 24-hour ambulatory BP); urine protein; and antihypertensive treatment by therapeutic class. Outcomes: The primary outcome is a composite event of a 50% reduction in eGFR, eGFR of <15 mL/min/1.73 m2, long-term dialysis or kidney transplant. Secondary outcomes include change in eGFR, adverse events, and PROs. Analytical Approach: Longitudinal models for dichotomous (proportional hazards or accelerated failure time) and continuous (generalized linear mixed models) clinical outcomes; multivariable linear regression for PROs. We will evaluate heterogeneity of treatment effect by CKD etiology and degree of proteinuria and will examine variation in hypertension management and outcomes based on socio-demographics. Limitations: Causal inference limited by observational analyses. Conclusions: PRESERVE will leverage the PCORnet infrastructure to conduct large-scale observational studies that address BP management knowledge gaps for pediatric CKD, focusing on outcomes that are meaningful to patients. Plain-Language Summary: Hypertension is a major modifiable contributor to loss of kidney function in chronic kidney disease (CKD). The purpose of PRESERVE is to provide evidence to inform shared decision-making regarding blood pressure management for children with CKD. PRESERVE is a consortium of 16 health care institutions in PCORnet, the National Patient-Centered Clinical Research Network, and includes electronic health record data for >19,000 children with CKD. PRESERVE will (1) expand the PCORnet infrastructure for research in pediatric CKD by adding kidney-specific variables and linking electronic health record data to other kidney disease databases; (2) compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; and (3) assess the lived experiences of patients and caregivers related to blood pressure management.
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Frontline clinicians responding to the COVID-19 pandemic are at increased risk of burnout, but less is known about the trajectory of clinician burnout as caseloads increase and decrease. Personal and professional resources, including self-efficacy and hospital support, can attenuate the risk of burnout. Yet, empirical data documenting how burnout and resources changed as the pandemic waxed and waned are limited. This intensive longitudinal prospective study employed ecological momentary assessment methods to examine trajectories of burnout and resources over the pandemic's first year in a New York City hospital. A 10-item survey was emailed every 5 days to frontline clinicians (physicians, nurses, and physician assistants). The primary outcome was a single-item validated measure of burnout; predictors included daily hospital COVID-19-related caseloads and personal and professional resources. Clinicians (n = 398) completed the initial survey and an average of 12 surveys over the year. Initially, 45.3% of staff reported burnout; over the year, 58.7% reported burnout. Following the initial COVID peak, caseloads declined, and burnout levels declined. During the second wave of COVID, as caseloads increased and remained elevated and personal and professional resource levels decreased, burnout increased. This novel application of intensive longitudinal assessment enabled ongoing surveillance of burnout and permitted us to evaluate how fluctuations in caseload intensity and personal and professional resources related to burnout over time. The surveillance data support the need for intensified resource allocation during prolonged pandemics.
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Esgotamento Profissional , COVID-19 , Humanos , Pandemias , Estudos Prospectivos , Esgotamento Psicológico , Avaliação Momentânea Ecológica , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Clinicians report training deficits in advance care planning (ACP), including limits to their understanding of cultural/spiritual influences on patient decision-making and skills in interdisciplinary teamwork. This study describes Advance Directives-Live Action Simulation Training (AD-LAST), an interdisciplinary experiential and didactic training program for discussing ACP and end-of-life (EOL) care. AD-LAST highlights cultural/spiritual variations in medical decision-making. METHODS: Prospective educational cohort study with pre-post intervention survey. AD-LAST incorporated standard curricular tools for didactic and experiential training in ACP/EOL communication. Study conducted in an urban community teaching hospital in Queens, NY, one of the most diverse counties in the USA. Participants included physicians, house staff, nurses, therapists, and other disciplines. AD-LAST format was a one-day workshop. The morning focused on didactic teaching using widely available curricular tools. The afternoon involved experiential practice with standardized patient-actors. Pre-post intervention questionnaires assessed ACP operational knowledge and self-efficacy (i.e., self-confidence in skills) in ACP and EOL communication. Repeated measure ANOVAs evaluated changes from pretest to posttest in knowledge and self-efficacy. RESULTS: A total of 163 clinical staff participated in 21 AD-LAST training sessions between August 2015 and January 2019. Participants displayed a significant increase from pretest to posttest in total knowledge (p < 0.001), ACP procedural knowledge (p < 0.001), ACP communication/relationships knowledge (p < 0.001), and self-efficacy (p < 0.001). Knowledge and self-efficacy were not correlated and represented independent outcomes. Postprogram evaluations showed greater than 96% of participants were highly satisfied with AD-LAST, especially the opportunity to practice skills in real-time and receive feedback from members of other professional groups. SIGNIFICANCE OF RESULTS: AD-LAST, a multifaceted training program deployed in an interdisciplinary setting, is effective for increasing ACP knowledge and self-efficacy, including the capacity to address cultural/spiritual concerns. The use of standard tools facilitates dissemination. The use of case simulations reinforces learning.
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Planejamento Antecipado de Cuidados , Assistência Terminal , Humanos , Estudos de Coortes , Estudos Prospectivos , Diretivas AntecipadasRESUMO
The Chinese American population is one of the fastest-growing communities in the United States, composed of â¼5.4 million people, and represents â¼5.5% of overseas Chinese populations. With an expected exponential population rise, Chinese American patients who experience serious illness or approach end-of-life (EOL) may find their cultural values influencing the medical care they receive. Palliative care clinicians must recognize diverse cultural beliefs and preferences of Chinese American patients and their families. In this study, we provide 10 cultural pearls to guide the provision of palliative and EOL care for Chinese American patients, including discussions of Chinese traditions, communication strategies for Chinese patients and families, advance care planning, and EOL care beliefs.
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Planejamento Antecipado de Cuidados , Cuidados Paliativos na Terminalidade da Vida , Cuidados Paliativos , Assistência Terminal , Humanos , Estados Unidos , AsiáticoRESUMO
As many people with intellectual disabilities (ID) live longer, the need for access to quality palliative care (PC) rises. People with ID realize significant barriers and inequities in accessing health care and PC. The need for integrated disability and PC services with extensive collaboration is great. The following tips are for PC clinicians caring for people with ID, their families, caregivers, and the community. While patient-centered care is difficult to distill into "tips," this article, written by an interdisciplinary team of PC and ID specialists, offers resources and references to improve the care provided to people with ID and serious illnesses.
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Cuidados Paliativos , HumanosRESUMO
Importance: The monoclonal antibody combination of casirivimab and imdevimab reduced viral load, hospitalization, or death when administered as a 1200-mg or greater intravenous (IV) dose in a phase 3 COVID-19 outpatient study. Subcutaneous (SC) and/or lower IV doses should increase accessibility and/or drug supplies for patients. Objective: To assess the virologic efficacy of casirivimab and imdevimab across different IV and SC doses compared with placebo. Design, Setting, and Participants: This phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study included outpatients with SARS-CoV-2 infection at 47 sites across the United States. Participants could be symptomatic or asymptomatic; symptomatic patients with risk factors for severe COVID-19 were excluded. Data were collected from December 15, 2020, to March 4, 2021. Interventions: Patients were randomized to a single IV dose (523 patients) of casirivimab and imdevimab at 300, 600, 1200, or 2400 mg or placebo; or a single SC dose (292 patients) of casirivimab and imdevimab at 600 or 1200 mg or placebo. Main Outcomes and Measures: The primary end point was the time-weighted average daily change from baseline (TWACB) in viral load from day 1 (baseline) through day 7 in patients seronegative for SARS-CoV-2 at baseline. Results: Among 815 randomized participants, 507 (282 randomized to IV treatment, 148 randomized to SC treatment, and 77 randomized to placebo) were seronegative at baseline and included in the primary efficacy analysis. Participants randomized to IV had a mean (SD) age of 34.6 (9.6) years (160 [44.6%] men; 14 [3.9%] Black; 121 [33.7%] Hispanic or Latino; 309 [86.1%] White); those randomized to SC had a mean age of 34.1 (10.0) years (102 [45.3%] men; 75 [34.7%] Hispanic or Latino; 6 [2.7%] Black; 190 [84.4%] White). All casirivimab and imdevimab treatments showed significant virologic reduction through day 7. Least-squares mean differences in TWACB viral load for casirivimab and imdevimab vs placebo ranged from -0.56 (95% CI; -0.89 to -0.24) log10 copies/mL for the 1200-mg IV dose to -0.71 (95% CI, -1.05 to -0.38) log10 copies/mL for the 2400-mg IV dose. There were no adverse safety signals or dose-related safety findings, grade 2 or greater infusion-related or hypersensitivity reactions, grade 3 or greater injection-site reactions, or fatalities. Two serious adverse events not related to COVID-19 or the study drug were reported. Conclusions and Relevance: In this randomized clinical trial including outpatients with asymptomatic and low-risk symptomatic SARS-CoV-2, all IV and SC doses of casirivimab and imdevimab comparably reduced viral load. Trial Registration: ClinicalTrials.gov Identifier: NCT04666441.
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Tratamento Farmacológico da COVID-19 , Adulto , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Masculino , Pacientes Ambulatoriais , SARS-CoV-2 , Estados UnidosRESUMO
BACKGROUND: Burnout during residency may be a function of intense professional demands and poor work/life balance. With the onset of the COVID-19 pandemic, NYC hospital systems were quickly overwhelmed, and trainees were required to perform beyond the usual clinical duties with less supervision and limited education. OBJECTIVE: The present longitudinal study examined the effects of COVID-19 caseload over time on burnout experienced by resident physicians and explored the effects of demographic characteristics and organizational and personal factors as predictors of burnout severity. METHODS: This study employed a prospective design with repeated measurements from April 2020 to June 2020. Participants were surveyed about their well-being every 5 days. Predictors included caseload, sociodemographic variables, self-efficacy, hospital support, perceived professional development, meaning in work, and postgraduate training level. RESULTS: In total, 54 resident physicians were recruited, of whom 50% reported burnout on initial assessment. Periods of higher caseload were associated with higher burnout. PGY-3 residents reported more burnout initially but appeared to recover faster compared to PGY-1 residents. Examined individually, higher self-efficacy, professional development, meaningful work, and hospital support were associated with lower burnout. When all four predictors were entered simultaneously, only self-efficacy was associated with burnout. However, professional development, meaningful work, and hospital support were associated with self-efficacy. CONCLUSION: Burnout among residency is prevalent and may have implications for burnout during later stages of a physician's career. Self-efficacy is associated with lower burnout and interventions to increase self-efficacy and the interpersonal factors that promote self-efficacy may improve physician physical and emotional well-being.
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Esgotamento Profissional , COVID-19 , Médicos , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , COVID-19/epidemiologia , Humanos , Estudos Longitudinais , Pandemias , Médicos/psicologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The open-label RECOVERY study reported improved survival in hospitalized, SARS-CoV-2 seronegative patients treated with casirivimab and imdevimab (CAS + IMD). METHODS: In this phase 1/2/3, double-blind, placebo-controlled trial conducted prior to widespread circulation of Delta and Omicron, hospitalized COVID-19 patients were randomized (1:1:1) to 2.4â g or 8.0â g CAS + IMD or placebo, and characterized at baseline for viral load and SARS-CoV-2 serostatus. RESULTS: In total, 1336 patients on low-flow or no supplemental (low-flow/no) oxygen were treated. The primary endpoint was met in seronegative patients, the least-squares mean difference (CAS + IMD versus placebo) for time-weighted average change from baseline in viral load through day 7 was -0.28 log10 copies/mL (95% confidence interval [CI], -.51 to -.05; P = .0172). The primary clinical analysis of death or mechanical ventilation from day 6 to 29 in patients with high viral load had a strong positive trend but did not reach significance. CAS + IMD numerically reduced all-cause mortality in seronegative patients through day 29 (relative risk reduction, 55.6%; 95% CI, 24.2%-74.0%). No safety concerns were noted. CONCLUSIONS: In hospitalized COVID-19 patients on low-flow/no oxygen, CAS + IMD reduced viral load and likely improves clinical outcomes in the overall population, with the benefit driven by seronegative patients, and no harm observed in seropositive patients. CLINICAL TRIALS REGISTRATION: NCT04426695.
Lay Summary . Monoclonal antibody therapies that block the virus that causes COVID-19 (SARS-CoV-2) can prevent patients from being hospitalized. We hypothesized that these antibodies may also benefit patients who are already hospitalized with COVID-19. Therefore, we performed a study to determine if the monoclonal antibody combination of casirivimab and imdevimab (CAS + IMD) can decrease the amount of virus in the nose of hospitalized patients and prevent the disease from becoming more severe. The study, conducted from June 2020 to April 2021, found that CAS + IMD treatment reduced the amount of virus in these patients, and may reduce their chance of dying or needing a ventilator (a machine that helps patients breathe). Patients were examined in 2 groups: those whose immune systems, at the start of the study, had not produced their own antibodies to fight SARS-CoV-2 (seronegative patients); or those that had already produced their own antibodies (seropositive patients) at the start of the study. Seronegative patients benefited the most from CAS + IMD. No safety concerns related to CAS + IMD were observed. These results demonstrate that monoclonal antibody therapy can help hospitalized patients with COVID-19 and may decrease their chances of needing assistance to breathe or dying.
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COVID-19 , Humanos , SARS-CoV-2 , Método Duplo-Cego , Tratamento Farmacológico da COVID-19RESUMO
Hypertensive crisis, especially in children, is a rare condition and is defined as a sudden and abrupt elevation in blood pressure that poses a threat of rapid onset of end-organ damage. Symptomatic hypertension requires urgent and thorough evaluation and management. In most patients with hypertensive crisis, a specific cause can be found with targeted investigation. History and physical examination will guide the assessment for cause and urgency of management. This article discusses common and rare causes of severe hypertension in infancy, childhood, and adulthood. Clinical features that indicate possible serious underlying disease associated with severe and symptomatic hypertension are outlined.
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Anti-Hipertensivos , Hipertensão , Adulto , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Criança , Emergências , Humanos , Hipertensão/complicações , Fatores de RiscoRESUMO
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.
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Reanimação Cardiopulmonar , Deficiência Intelectual , Adulto , Estudos de Coortes , Morte , Humanos , Intubação Intratraqueal/métodos , Projetos Piloto , Ordens quanto à Conduta (Ética Médica)RESUMO
BACKGROUND: The revised 2018 ISN/RPS Classification System for lupus nephritis (LN) includes calculations for both activity index (A.I.) and chronicity index (C.I.). Unchanged were the thresholds of < 25%, 25-50%, and > 50% crescents to distinguish between mild, moderate, and severe activity/chronicity. We aimed to evaluate these thresholds for percent crescents in childhood-onset LN. METHODS: Eighty-six subjects < 21 years of age were enrolled from the Pediatric Glomerulonephritis with Crescents Registry, a retrospective multi-center cohort sponsored by the Pediatric Nephrology Research Consortium. Thresholds of 10%, 25%, and 50% for both cellular/fibrocellular and fibrous crescents were interrogated for primary outcomes of kidney failure, eGFR, and eGFR slope. RESULTS: Median age at time of initial biopsy was 14 years (range 1-21). Median follow-up time was 3 years (range 1-11). Cumulative incidence of kidney failure was 6% at 1 year and 10% at latest follow-up. Median eGFR slope was - 18 mL/1.73 m2/min (IQR - 51 to + 8) at 1 year and - 3 mL/min/1.73 m2/year (IQR - 19 to + 6) at latest follow-up. We found no difference in kidney failure at the proposed < 25% and 25-50% cellular crescents thresholds, and thus added a new provisional threshold of 10% that better predicted outcomes in children. Moreover, use of 10% and 25% thresholds for fibrous crescents showed a fourfold and sevenfold increase in risk of kidney failure. CONCLUSIONS: In children with crescentic LN, use of 10% and 25% thresholds for cellular crescents better reflects disease activity, while these thresholds for fibrous crescents better discriminates kidney disease outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Nefrite Lúpica , Nefrologia , Insuficiência Renal , Humanos , Criança , Lactente , Pré-Escolar , Adolescente , Adulto Jovem , Adulto , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/epidemiologia , Glomérulos Renais/patologia , Rim/patologiaRESUMO
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.
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Estado Terminal , Tomada de Decisões , Cuidados Críticos , Estado Terminal/terapia , Pesar , Humanos , Unidades de Terapia IntensivaRESUMO
BACKGROUND: In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. METHODS: In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated. RESULTS: Covid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups. CONCLUSIONS: REGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.).