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BACKGROUND: Rising rates of psychological distress (symptoms of depression, anxiety, and stress) among adults in the United States necessitate effective mental wellness interventions. Despite the prevalence of smartphone app-based programs, research on their efficacy is limited, with only 14% showing clinically validated evidence. Our study evaluates Noom Mood, a commercially available smartphone-based app that uses cognitive behavioral therapy and mindfulness-based programming. In this study, we address gaps in the existing literature by examining postintervention outcomes and the broader impact on mental wellness. OBJECTIVE: Noom Mood is a smartphone-based mental wellness program designed to be used by the general population. This prospective study evaluates the efficacy and postintervention outcomes of Noom Mood. We aim to address the rising psychological distress among adults in the United States. METHODS: A 1-arm study design was used, with participants having access to the Noom Mood program for 16 weeks (N=273). Surveys were conducted at baseline, week 4, week 8, week 12, week 16, and week 32 (16 weeks' postprogram follow-up). This study assessed a range of mental health outcomes, including anxiety symptoms, depressive symptoms, perceived stress, well-being, quality of life, coping, emotion regulation, sleep, and workplace productivity (absenteeism or presenteeism). RESULTS: The mean age of participants was 40.5 (SD 11.7) years. Statistically significant improvements in anxiety symptoms, depressive symptoms, and perceived stress were observed by week 4 and maintained through the 16-week intervention and the 32-week follow-up. The largest changes were observed in the first 4 weeks (29% lower, 25% lower, and 15% lower for anxiety symptoms, depressive symptoms, and perceived stress, respectively), and only small improvements were observed afterward. Reductions in clinically relevant anxiety (7-item generalized anxiety disorder scale) and depression (8-item Patient Health Questionnaire depression scale) criteria were also maintained from program initiation through the 16-week intervention and the 32-week follow-up. Work productivity also showed statistically significant results, with participants gaining 2.57 productive work days from baseline at 16 weeks, and remaining relatively stable (2.23 productive work days gained) at follow-up (32 weeks). Additionally, effects across all coping, sleep disturbance (23% lower at 32 weeks), and emotion dysregulation variables exhibited positive and significant trends at all time points (15% higher, 23% lower, and 25% higher respectively at 32 weeks). CONCLUSIONS: This study contributes insights into the promising positive impact of Noom Mood on mental health and well-being outcomes, extending beyond the intervention phase. Though more rigorous studies are necessary to understand the mechanism of action at play, this exploratory study addresses critical gaps in the literature, highlighting the potential of smartphone-based mental wellness programs to lessen barriers to mental health support and improve diverse dimensions of well-being. Future research should explore the scalability, feasibility, and long-term adherence of such interventions across diverse populations.
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Aplicaciones Móviles , Humanos , Estudios Prospectivos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Encuestas y Cuestionarios , Aplicaciones Móviles/estadística & datos numéricos , Aplicaciones Móviles/normas , Promoción de la Salud/métodos , Terapia Cognitivo-Conductual/métodos , Terapia Cognitivo-Conductual/normas , Evaluación de Programas y Proyectos de Salud/métodos , Estados Unidos , Atención Plena/métodos , Calidad de Vida/psicologíaRESUMEN
We conducted a prospective single-centre cohort study of 104 multi-ethnic severe COVID-19 survivors from the first wave of the pandemic 15 months after hospitalisation. Of those who were assessed at 4 and 15 months, improvement of ground glass opacities correlated with worsened fibrotic reticulations. Despite a high prevalence of fibrotic patterns (64%), pulmonary function, grip strength, 6 min walk distance and frailty normalised. Overall, dyspnoea, cough and exhaustion did not improve and were not correlated with pulmonary function or radiographic fibrosis at 15 months, suggesting non-respiratory aetiologies. Monitoring persistent, and often subclinical, fibrotic interstitial abnormalities will be needed to determine their potential for future progression.
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COVID-19 , Fibrosis Pulmonar , Humanos , Fibrosis Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/etiología , Tolerancia al Ejercicio , Estudios Prospectivos , Estudios de CohortesRESUMEN
The incorporation of energetic helium gaseous species into materials such as tungsten (W) imparts intrinsic surface fragility, yielding fuzzy tungsten. To enhance the robustness of the surface layers, aluminum oxide (AlOx) was deposited by atomic layer deposition into the fuzzy W. The conformally deposited ceramic yields a new class of surface composites. Structural characterization of the fuzzy W-AlOx composites through nanoindentation testing indicated enhanced indentation modulus (Eind) and hardness (Hind) and was modeled through various rules of mixtures approaches. The distribution of AlOx in fuzzy W was explored and a systematic study of the extent of incorporation of the AlOx into the fuzzy W was carried out. The synthesized composites may be utilized for improved structural characteristics, e.g., in reducing crack initiation and fracture.
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We investigate self-appraisals over time using a cognitive-ecological approach. We assume that ecologically, negative person attributes are more diverse than positive ones, while positive person attributes are more frequent than negative ones. We combine these ecological properties with the cognitive process of similarity- and differences-based social comparisons to predict temporal self-appraisals. The resulting cognitive-ecological model predicts that people should evaluate similarities with themselves over time positively, whereas differences would be evaluated more negatively. However, because positive attributes are reinforced over time relative to negative attributes, we predicted an asymmetry to emerge such that distinct attributes of the past self (past differences) would be most negative. Six experiments (total N = 1,796) and an integrative data analysis confirmed the cognitive-ecological model's predictions for temporal self-appraisals. However, we found no evidence for motivated self-perception across time. We discuss the implications of these findings for temporal self-appraisal theory and other aspects of self and identity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Rationale: Patients with obesity are at increased risk for developing acute respiratory distress syndrome (ARDS). Some centers consider obesity a relative contraindication to receiving extracorporeal membrane oxygenation (ECMO) support, despite growing implementation of ECMO for ARDS in the general population. Objectives: To investigate the association between obesity and mortality in patients with ARDS receiving ECMO. Methods: In this large, international, multicenter, retrospective cohort study, we evaluated the association of obesity, defined as body mass index ⩾ 30 kg/m2, with ICU mortality in patients receiving ECMO for ARDS by performing adjusted multivariable logistic regression and propensity score matching. Measurements and Main Results: Of 790 patients with ARDS receiving ECMO in our study, 320 had obesity. Of those, 24.1% died in the ICU, compared with 35.3% of patients without obesity (P < 0.001). In adjusted models, obesity was associated with lower ICU mortality (odds ratio, 0.63 [95% confidence interval, 0.43-0.93]; P = 0.018). Examined as a continuous variable, higher body mass index was associated with decreased ICU mortality in multivariable regression (odds ratio, 0.97 [95% confidence interval, 0.95-1.00]; P = 0.023). In propensity score matching of 199 patients with obesity to 199 patients without, patients with obesity had a lower probability of ICU death than those without (22.6% vs. 35.2%; P = 0.007). Conclusions: Among patients receiving ECMO for ARDS, those with obesity had lower ICU mortality than patients without obesity in multivariable and propensity score matching analyses. Our findings support the notion that obesity should not be considered a general contraindication to ECMO.
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Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria , Humanos , Estudios Retrospectivos , Obesidad/complicaciones , Obesidad/terapia , Índice de Masa Corporal , Síndrome de Dificultad Respiratoria/terapiaRESUMEN
BACKGROUND: The Noom Weight program is a smartphone-based weight management program that uses cognitive behavioral therapy techniques to motivate users to achieve weight loss through a comprehensive lifestyle intervention. OBJECTIVE: This retrospective database analysis aimed to evaluate the impact of Noom Weight use on health care resource utilization (HRU) and health care costs among individuals with overweight and obesity. METHODS: Electronic health record data, insurance claims data, and Noom Weight program data were used to conduct the analysis. The study included 43,047 Noom Weight users and 14,555 non-Noom Weight users aged between 18 and 80 years with a BMI of ≥25 kg/m² and residing in the United States. The index date was defined as the first day of a 3-month treatment window during which Noom Weight was used at least once per week on average. Inverse probability treatment weighting was used to balance sociodemographic covariates between the 2 cohorts. HRU and costs for inpatient visits, outpatient visits, telehealth visits, surgeries, and prescriptions were analyzed. RESULTS: Within 12 months after the index date, Noom Weight users had less inpatient costs (mean difference [MD] -US $20.10, 95% CI -US $30.08 to -US $10.12), less outpatient costs (MD -US $124.33, 95% CI -US $159.76 to -US $88.89), less overall prescription costs (MD -US $313.82, 95% CI -US $565.42 to -US $62.21), and less overall health care costs (MD -US $450.39, 95% CI -US $706.28 to -US $194.50) per user than non-Noom Weight users. In terms of HRU, Noom Weight users had fewer inpatient visits (MD -0.03, 95% CI -0.04 to -0.03), fewer outpatient visits (MD -0.78, 95% CI -0.93 to -0.62), fewer surgeries (MD -0.01, 95% CI -0.01 to 0.00), and fewer prescriptions (MD -1.39, 95% CI -1.76 to -1.03) per user than non-Noom Weight users. Among a subset of individuals with 24-month follow-up data, Noom Weight users incurred lower overall prescription costs (MD -US $1139.52, 95% CI -US $1972.21 to -US $306.83) and lower overall health care costs (MD -US $1219.06, 95% CI -US $2061.56 to -US $376.55) per user than non-Noom Weight users. The key differences were associated with reduced prescription use. CONCLUSIONS: Noom Weight use is associated with lower HRU and costs than non-Noom Weight use, with potential cost savings of up to US $1219.06 per user at 24 months after the index date. These findings suggest that Noom Weight could be a cost-effective weight management program for individuals with overweight and obesity. This study provides valuable evidence for health care providers and payers in evaluating the potential benefits of digital weight loss interventions such as Noom Weight.
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Sobrepeso , Telemedicina , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Obesidad/terapia , Aceptación de la Atención de SaludRESUMEN
OBJECTIVES: Pulmonary fibrosis is a feared complication of COVID-19. To characterize the risks and outcomes associated with fibrotic-like radiographic abnormalities in patients with COVID-19-related acute respiratory distress syndrome (ARDS) and chronic critical illness. DESIGN: Single-center prospective cohort study. SETTING: We examined chest CT scans performed between ICU discharge and 30 days after hospital discharge using established methods to quantify nonfibrotic and fibrotic-like patterns. PATIENTS: Adults hospitalized with COVID-19-related ARDS and chronic critical illness (> 21 d of mechanical ventilation, tracheostomy, and survival to ICU discharge) between March 2020 and May 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We tested associations of fibrotic-like patterns with clinical characteristics and biomarkers, and with time to mechanical ventilator liberation and 6-month survival, controlling for demographics, comorbidities, and COVID-19 therapies. A total of 141 of 616 adults (23%) with COVID-19-related ARDS developed chronic critical illness, and 64 of 141 (46%) had a chest CT a median (interquartile range) 66 days (42-82 d) after intubation. Fifty-five percent had fibrotic-like patterns characterized by reticulations and/or traction bronchiectasis. In adjusted analyses, interleukin-6 level on the day of intubation was associated with fibrotic-like patterns (odds ratio, 4.40 per quartile change; 95% CI, 1.90-10.1 per quartile change). Other inflammatory biomarkers, Sequential Organ Failure Assessment score, age, tidal volume, driving pressure, and ventilator days were not. Fibrotic-like patterns were not associated with longer time to mechanical ventilator liberation or worse 6-month survival. CONCLUSIONS: Approximately half of adults with COVID-19-associated chronic critical illness have fibrotic-like patterns that are associated with higher interleukin-6 levels at intubation. Fibrotic-like patterns are not associated with longer time to liberation from mechanical ventilation or worse 6-month survival.
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COVID-19 , Síndrome de Dificultad Respiratoria , Adulto , Humanos , COVID-19/diagnóstico por imagen , COVID-19/complicaciones , Enfermedad Crítica/terapia , Estudios Prospectivos , Interleucina-6 , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/terapia , Respiración Artificial/efectos adversos , BiomarcadoresRESUMEN
In multisensory environments, our brains perform causal inference to estimate which sources produce specific sensory signals. Decades of research have revealed the dynamics which underlie this process of causal inference for multisensory (audiovisual) signals, including how temporal, spatial, and semantic relationships between stimuli influence the brain's decision about whether to integrate or segregate. However, presently, very little is known about the relationship between metacognition and multisensory integration, and the characteristics of perceptual confidence for audiovisual signals. In this investigation, we ask two questions about the relationship between metacognition and multisensory causal inference: are observers' confidence ratings for judgments about Congruent, McGurk, and Rarely Integrated speech similar, or different? And do confidence judgments distinguish between these three scenarios when the perceived syllable is identical? To answer these questions, 92 online participants completed experiments where on each trial, participants reported which syllable they perceived, and rated confidence in their judgment. Results from Experiment 1 showed that confidence ratings were quite similar across Congruent speech, McGurk speech, and Rarely Integrated speech. In Experiment 2, when the perceived syllable for congruent and McGurk videos was matched, confidence scores were higher for congruent stimuli compared to McGurk stimuli. In Experiment 3, when the perceived syllable was matched between McGurk and Rarely Integrated stimuli, confidence judgments were similar between the two conditions. Together, these results provide evidence of the capacities and limitations of metacognition's ability to distinguish between different sources of multisensory information.
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Metacognición , Percepción del Habla , Humanos , Percepción Visual , Habla , Percepción Auditiva , Estimulación Acústica/métodos , Estimulación Luminosa/métodosRESUMEN
Hospitalized individuals in the United States with limited English proficiency (LEP) may experience complications when receiving hospital care. Grounded in the ethical principles of chaplaincy and motivated by the desire to address inequitable health service provision, we developed the Cross-Language Chaplaincy Introduction Guidebook. The Guidebook introduces chaplaincy in 20 different languages with the goal of improving chaplain accessibility. We report on the rigorous development of the Guidebook and how to integrate the resource clinically.
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Dominio Limitado del Inglés , Cuidado Pastoral , Terapias Espirituales , Humanos , Estados Unidos , Lenguaje , CleroRESUMEN
BACKGROUND: Chronic sleep disturbance is prevalent among United States employees and associated with costly productivity impairment. Mindfulness interventions improve sleep (ie, insomnia and daytime sleepiness) and productivity outcomes, and mobile apps provide scalable means of intervention delivery. However, few studies have examined the effects of mindfulness mobile apps on employees, and no research to date has tested the role of sleep improvement as a potential mechanism of action for productivity outcomes. OBJECTIVE: This study examined the effects of Calm, a consumer-based mindfulness app, and sleep coaching, on productivity impairment among retail employees through the indirect effects of changes in insomnia and daytime sleepiness. METHODS: This study was a secondary analysis of data from a randomized controlled trial (N=1029) comparing the use of Calm (n=585, 56.9%) to a waitlist control (n=444, 43.2%) for 8 weeks among employees of a large retail employer in the United States. A subset of individuals with elevated insomnia symptoms also had access to brief sleep coaching with Calm (n=101, 9.8%). Insomnia symptom severity, daytime sleepiness, and productivity impairment (ie, absenteeism, presenteeism, overall productivity impairment, and non-work activity impairment) were assessed at baseline and weeks 2, 4, 6, and 8. Indirect effects were evaluated with latent growth curve modeling to test whether the Calm intervention (Calm group vs waitlist control) was effective in reducing work productivity impairment through changes in sleep disturbance. RESULTS: No significant main effects of Calm intervention on productivity impairment were detected for any outcome at α level of .05, with the exception of non-work activity impairment models, in which Calm intervention reduced non-work activity impairment over time (P=.01 and P=.02 for insomnia and sleepiness models, respectively). Significant indirect effects of insomnia were detected for presenteeism (P=.002), overall work productivity (P=.01), and non-work activity impairment (P=.002); Calm intervention produced significantly greater reductions in insomnia symptoms (relative to waitlist control), and decreases in insomnia were associated with decreases in work productivity impairment. There was no significant indirect effect of change in insomnia on changes in absenteeism (P=.20). Furthermore, we detected no significant indirect effects of daytime sleepiness on productivity impairment. CONCLUSIONS: We found that Calm (plus sleep coaching for a small subset of individuals) had beneficial effects on employee sleep, and these benefits on sleep were related to indirect effects on productivity impairment (ie, presenteeism, overall work productivity impairment, and non-work activity impairment). There were no overall main effects of Calm intervention on productivity impairment; however, insomnia appears to be a mechanism associated with benefits for employee productivity. This is one of the first studies to suggest that sleep benefits of a mindfulness mobile app may also indirectly relate to benefits for workplace productivity. TRIAL REGISTRATION: ClinicalTrials.gov NCT05120310; https://clinicaltrials.gov/ct2/show/NCT05120310.
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Trastornos de Somnolencia Excesiva , Atención Plena , Aplicaciones Móviles , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Sueño , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Estados UnidosRESUMEN
OBJECTIVES: Evaluate the efficacy of interventions to improve symptoms for ICU surrogates at highest risk of developing psychologic distress: those facing end-of-life care decisions. DATA SOURCES: MEDLINE, CINAHL, PsycInfo, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched through April 16, 2022. STUDY SELECTION: Following an a priori protocol, randomized trials of interventions delivered to surrogates of adult ICU patients who died or had high likelihood of mortality evaluating surrogate symptoms were identified. DATA EXTRACTION: Two reviewers performed screening and data extraction and assessed risk of bias (Cochrane Risk of Bias [RoB] 2 tool). Trials were eligible for meta-analysis if group mean symptom scores were provided at 3 or 6 months. Pooled effects were estimated using a random effects model. Heterogeneity was assessed (Cochrane Q, I2 ). Certainty of evidence was assessed (Grading of Recommendations Assessment, Development and Evaluation). DATA SYNTHESIS: Of 1,660 records, 10 trials met inclusion criteria representing 3,824 surrogates; eight were included in the meta-analysis. Overall RoB was rated Some Concerns. Most ( n = 8) interventions focused on improving communication and enhancing psychologic support in the ICU. All trials measured anxiety, depression, and posttraumatic stress. Significant improvement was seen at 3 months (depression, mean difference [MD], -0.68; 95% CI, -1.14 to -0.22, moderate certainty; posttraumatic stress, standardized MD, -0.25; 95% CI, -0.49 to -0.01, very low certainty) and 6 months (anxiety, MD, -0.70; 95% CI, -1.18 to -0.22, moderate certainty). Sensitivity analyses suggest significant findings may be unstable. Subgroup analyses demonstrated differences in effect by trial location, interventionist, and intervention dose. CONCLUSIONS: Communication and psychological support interventions in the ICU yielded small but significant improvement in psychological symptoms with moderate to very low certainty evidence in a prognostically-enriched sample of ICU surrogates facing end-of-life care decisions. A new approach to interventions that extend beyond the ICU may be needed.
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Ansiedad , Calidad de Vida , Adulto , Ansiedad/psicología , Ansiedad/terapia , Trastornos de Ansiedad , Muerte , Humanos , Unidades de Cuidados IntensivosRESUMEN
Polarization and extremism are often viewed as the product of psychological biases or social influences, yet they still occur in the absence of any bias or irrational thinking. We show that individual decision-makers implementing optimal dynamic decision strategies will become polarized, forming extreme views relative to the true information in their environment by virtue of how they sample new information. Extreme evidence enables decision makers to stop considering new information, whereas weak or moderate evidence is unlikely to trigger a decision and is thus under-sampled. We show that this information polarization effect arises empirically across choice domains including politically-charged, affect-rich and affect-poor, and simple perceptual decisions. However, this effect can be disincentivized by asking participants to make a judgment about the difference between two options (estimation) rather than deciding. We experimentally test this intervention by manipulating participants' inference goals (decision vs inference) in an information sampling task. We show that participants in the estimation condition collect more information, hold less extreme views, and are less polarized than those in the decision condition. Estimation goals therefore offer a theoretically-motivated intervention that could be used to alleviate polarization and extremism in situations where people traditionally intend to decide.
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Toma de Decisiones , Juicio , Sesgo , HumanosRESUMEN
Respiratory failure in COVID-19 is characterized by widespread disruption of the lung's alveolar gas exchange interface. To elucidate determinants of alveolar lung damage, we performed epithelial and immune cell profiling in lungs from 24 COVID-19 autopsies and 43 uninfected organ donors ages 18-92 years. We found marked loss of type 2 alveolar epithelial (T2AE) cells and increased perialveolar lymphocyte cytotoxicity in all fatal COVID-19 cases, even at early stages before typical patterns of acute lung injury are histologically apparent. In lungs from uninfected organ donors, there was also progressive loss of T2AE cells with increasing age, which may increase susceptibility to COVID-19-mediated lung damage in older individuals. In the fatal COVID-19 cases, macrophage infiltration differed according to the histopathological pattern of lung injury. In cases with acute lung injury, we found accumulation of CD4+ macrophages that expressed distinctly high levels of T cell activation and costimulation genes and strongly correlated with increased extent of alveolar epithelial cell depletion and CD8+ T cell cytotoxicity. Together, our results show that T2AE cell deficiency may underlie age-related COVID-19 risk and initiate alveolar dysfunction shortly after infection, and we define immune cell mediators that may contribute to alveolar injury in distinct pathological stages of fatal COVID-19.
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Lesión Pulmonar Aguda , COVID-19 , Lesión Pulmonar Aguda/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Células Epiteliales Alveolares/patología , Autopsia , Humanos , Pulmón/patología , Persona de Mediana Edad , Adulto JovenAsunto(s)
COVID-19 , Enfermedad Crítica , Enfermedad Crítica/terapia , Humanos , SARS-CoV-2 , SobrevivientesRESUMEN
Importance: The psychological symptoms associated with having a family member admitted to the intensive care unit (ICU) during the COVID-19 pandemic are not well defined. Objective: To examine the prevalence of symptoms of stress-related disorders, primarily posttraumatic stress disorder (PTSD), in family members of patients admitted to the ICU with COVID-19 approximately 90 days after admission. Design, Setting, and Participants: This prospective, multisite, mixed-methods observational cohort study assessed 330 family members of patients admitted to the ICU (except in New York City, which had a random sample of 25% of all admitted patients per month) between February 1 and July 31, 2020, at 8 academic-affiliated and 4 community-based hospitals in 5 US states. Exposure: Having a family member in the ICU with COVID-19. Main Outcomes and Measures: Symptoms of PTSD at 3 months, as defined by a score of 10 or higher on the Impact of Events Scale 6 (IES-6). Results: A total of 330 participants (mean [SD] age, 51.2 [15.1] years; 228 [69.1%] women; 150 [52.8%] White; 92 [29.8%] Hispanic) were surveyed at the 3-month time point. Most individuals were the patients' child (129 [40.6%]) or spouse or partner (81 [25.5%]). The mean (SD) IES-6 score at 3 months was 11.9 (6.1), with 201 of 316 respondents (63.6%) having scores of 10 or higher, indicating significant symptoms of PTSD. Female participants had an adjusted mean IES-6 score of 2.6 points higher (95% CI, 1.4-3.8; P < .001) than male participants, whereas Hispanic participants scored a mean of 2.7 points higher compared with non-Hispanic participants (95% CI, 1.0-4.3; P = .002). Those with graduate school experience had an adjusted mean score of 3.3 points lower (95% CI, 1.5-5.1; P < .001) compared with those with up to a high school degree or equivalent. Qualitative analyses found no substantive differences in the emotional or communication-related experiences between those with high vs low PTSD scores, but those with higher scores exhibited more distrust of practitioners. Conclusions and Relevance: In this cohort study, symptoms of PTSD among family members of ICU patients with COVID-19 were high. Hispanic ethnicity and female gender were associated with higher symptoms. Those with higher scores reported more distrust of practitioners.
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COVID-19 , Trastornos por Estrés Postraumático , COVID-19/epidemiología , Niño , Estudios de Cohortes , Familia/psicología , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Pandemias , Estudios Prospectivos , Trastornos por Estrés Postraumático/psicologíaRESUMEN
BACKGROUND: Novel regimens have revolutionized multidrug-resistant tuberculosis (MDR-TB) treatment; however, medication adherence remains challenging and poorly characterized. We hypothesized that bedaquiline adherence, measured using electronic dose monitoring, would predict MDR-TB treatment outcomes. SETTING: This is a prospective cohort study conducted in KwaZulu-Natal, South Africa. METHODS: Adults with MDR-TB and HIV initiating bedaquiline and on antiretroviral therapy (ART) were eligible. Separate electronic dose monitoring devices measured bedaquiline and ART adherence through 6 months, calculated as observed versus expected doses. Whole-genome sequencing was performed to identify bedaquiline resistance-associated variants. RESULTS: From November 2016 through February 2018, 199 participants with MDR-TB and HIV were enrolled and followed up through treatment completion (median 17.2 months interquartile range 12.2-19.6). The median bedaquiline adherence was higher than ART adherence (97 vs. 89%, P < 0.001) but correlated (r2 = 0.68, P < 0.001). High bedaquiline adherence (≥90%) compared with lower adherence was associated with improved end of treatment successful outcome (83.4% vs. 46.3%, P < 0.001), decreased mortality (11.0% vs. 29.6% P = 0.004), and improved retention in care through end of treatment (94.5% vs. 79.6% P = 0.002). Modeling identified a highly significant but linear association between bedaquiline adherence and outcome. On multivariable analysis, bedaquiline adherence was independently associated with mortality and outcome. Bedaquiline resistance-associated variants were seen in 12% (7/57) of sequenced isolates (7% baseline, 5% emergent) with only 28.6% experiencing successful treatment outcome. CONCLUSIONS: Bedaquiline adherence through 6 months independently predicted end of MDR-TB treatment outcome, but a specific bedaquiline adherence threshold was not identified. Interventions to optimize bedaquiline adherence are urgently needed to improve MDR-TB HIV treatment outcomes.
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Tuberculosis Resistente a Múltiples Medicamentos , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Antituberculosos/uso terapéutico , Diarilquinolinas , Electrónica , Infecciones por VIH/complicaciones , Humanos , Estudios Prospectivos , Sudáfrica , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/complicacionesRESUMEN
Acute cardiac injury is prevalent in critical COVID-19 and associated with increased mortality. Its etiology remains debated, as initially presumed causes - myocarditis and cardiac necrosis - have proved uncommon. To elucidate the pathophysiology of COVID-19-associated cardiac injury, we conducted a prospective study of the first 69 consecutive COVID-19 decedents at CUIMC in New York City. Of 6 acute cardiac histopathologic features, presence of microthrombi was the most commonly detected among our cohort. We tested associations of cardiac microthrombi with biomarkers of inflammation, cardiac injury, and fibrinolysis and with in-hospital antiplatelet therapy, therapeutic anticoagulation, and corticosteroid treatment, while adjusting for multiple clinical factors, including COVID-19 therapies. Higher peak erythrocyte sedimentation rate and C-reactive protein were independently associated with increased odds of microthrombi, supporting an immunothrombotic etiology. Using single-nuclei RNA-sequencing analysis on 3 patients with and 4 patients without cardiac microthrombi, we discovered an enrichment of prothrombotic/antifibrinolytic, extracellular matrix remodeling, and immune-potentiating signaling among cardiac fibroblasts in microthrombi-positive, relative to microthrombi-negative, COVID-19 hearts. Non-COVID-19, nonfailing hearts were used as reference controls. Our study identifies a specific transcriptomic signature in cardiac fibroblasts as a salient feature of microthrombi-positive COVID-19 hearts. Our findings warrant further mechanistic study as cardiac fibroblasts may represent a potential therapeutic target for COVID-19-associated cardiac microthrombi.