Psychological Attachment Orientation and Long-Term Posttraumatic Stress Symptoms Among Family Members of ICU Patients.

To determine the degree to which an ICU patient's family member having an "anxious" psychologic attachment orientation is a risk factor for developing long-term posttraumatic stress disorder (PTSD) symptoms following patient ICU discharge or death. DESIGN: Prospective cohort study. SETTING: Single academic neuroscience ICU from November 2017 to September 2020. PARTICIPANTS: Consecutively enrolled sample of family members, one for each ICU patient with a minimum length of stay of 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Near time of ICU discharge or patient death, we determined each participant's psychologic attachment orientation as anxious versus nonanxious via a brief standard survey tool, the Relationship Questionnaire, and measured other participant and patient characteristics as potential covariates. Six months after discharge or death, each participant completed the Impact of Events Scale-Revised (IES-R) to measure PTSD symptoms, with a score of greater than 24 indicative of clinically significant symptoms. Among 162 total participants, 10 of 27 participants (37.0%) with an anxious attachment orientation reported 6-month PTSD symptoms, compared with 24 of 135 nonanxious participants (17.8%) (relative risk, 2.08; 95% CI, 1.13-3.84; p = 0.02; risk difference 19.2%). In a subsequent univariate analysis of participant and patient covariates, anxious attachment orientation, participant Hispanic ethnicity, prior experience as a care partner of a patient with a disability, and participation in 3 or more formal ICU family meetings were all associated with 6-month PTSD symptoms. In a multiple logistic regression, anxious attachment remained an independent predictor of 6-month PTSD symptoms (odds ratio [OR], 3.64; 95% CI, 1.35-9.77; p = 0.01), as did Hispanic ethnicity (OR, 4.72; 95% CI, 1.34-16.6; p = 0.01) and participation in three or more ICU family meetings (odds ratio, 2.97; 95% CI, 1.14-7.68; p = 0.02). CONCLUSIONS: An anxious psychologic attachment orientation is associated with double the risk of long-term PTSD symptoms among family members of ICU patients. Future interventions designed to decrease risk of adverse psychologic outcomes among ICU families could be initially tested for efficacy amongst those who fall into this high-risk category.

Stressors on frontline healthcare workers during the COVID-19 pandemic: a focus on moral injury and implications for the future.

OBJECTIVE: The COVID-19 pandemic has placed a psychological strain on health care workers (HCWs). To provide effective support, it is important to explore the stressors that HCWs face that place them at risk of negative psychological outcomes. However, there is a limited number of systematic qualitative studies on the stressors that HCWs faced in the United States of America (USA) during the first wave of the pandemic. Therefore, we explored the stressors that frontline HCWs in the USA experienced during the initial phase of the pandemic. METHODS: We performed a qualitative study based on open-ended, semi-structured, one-on-one interviews conducted virtually among HCWs from June 1st to July 18th, 2020. We interviewed frontline HCWs (N = 45) including physicians, nurses, respiratory therapists, and patient care assistants who worked in various specialties and roles in 3 health systems across Connecticut, USA. We offered participants a $25 gift card as a token of appreciation. We used inductive techniques derived from grounded theory to develop themes. RESULTS: We identified 3 main themes related to stressors experienced by HCWs during the initial phase of the pandemic namely: (1) Stress of witnessing an unprecedented number of deaths and the impact on patient families; (2) Stress of changing work environment and unmet professional expectations and; (3) Concern for safety in personal life. Furthermore, we highlight experiences that HCWs faced that place them at risk of developing a moral injury. CONCLUSIONS: Our findings highlight stressors faced by HCWs that could aid in the provision of well-guided support to HCWs in the present and post-pandemic era.

How to lead health care workers during unprecedented crises: A qualitative study of the COVID-19 pandemic in Connecticut, USA.

Health Care Leaders (HCLs) faced unprecedented challenges during the initial phases of the COVID-19 pandemic. Leaders played an important role in shaping the experiences of Health Care Workers (HCWs) during this time. However, research is needed on how HCWs experienced and characterized HCLs' response and support. The aim of our study was to examine HCWs' experiences with leadership and to identify aspects of HCLs' response that were effective in supporting HCWs in their roles during the early phases of the pandemic. This was a qualitative study based on open-ended semi-structured interviews conducted (June 1- July 18, 2020) with frontline HCWs during the first wave of the COVID-19 pandemic in Connecticut, USA. Participants (N = 45) included physicians, nurses, respiratory therapists and patient care assistants who worked in inpatient and outpatient settings in various specialties, roles and 3 health systems across Connecticut, USA during the COVID-19 pandemic. Participants were offered a $25 gift card as an incentive for participation. We used inductive techniques derived from grounded theory to develop themes. We identified 6 main themes related to leadership response and support of HCWs during the pandemic namely: 1) Effective communication and transparency; 2) Prioritizing their health and safety; 3) Employee scheduling considerations: autonomy, assignment support and respite; 4) Appreciation- financial and nonfinancial; 5) Showing up and listening and 6) Stepping up with resources. Our findings can inform leadership responses to future pandemics and other unanticipated crises leading to strengthening of the health care system as a whole.

Engagement in Non-Medical End-of-Life Planning by Older Adults.

CONTEXT: While medical end-of-life planning has been well characterized, less is known about non-medical planning to prepare for the end of life. OBJECTIVES: To determine the prevalence of engagement in non-medical end-of-life (EOL) planning and its relationship to medical EOL planning. METHODS: Three hundred and four persons age 65 and older recruited from physician offices and a senior center were administered an in-person interview asking about participation in the following non-medical EOL planning behaviors: moving to a location with more help, teaching someone to do things around the house, purchasing long-term care insurance, telling someone the location of important documents, preparing a financial will, conveying wishes for funeral arrangements, purchasing a cemetery plot, and prepaying for a funeral. RESULTS: Prevalence of participation in the different non-medical EOL planning activities varied widely, from 8% for prepaying for a funeral to 84% for telling someone the location of important documents. There was little overlap in the factors associated with participation in each activity. Conveying wishes for funeral arrangements and completing a financial will were associated with completing a living will (OR 2.69, 95% CI 1.51, 4.78; OR 6.70, 95% CI 3.18, 14.15) and communication about quality versus quantity of life (OR 4.52, 95% CI 2.54, 8.04; OR 2.47, 95% CI 1.25, 4.86). CONCLUSION: There is variability in both the prevalence of and factors associated with engagement in non-medical EOL planning activities. The association of non-medical with medical planning activities supports the utility of programs assisting individuals with broad engagement in EOL planning.

Psychological Attachment Orientations of Surrogate Decision-Makers and Goals-of-Care Decisions for Brain Injury Patients in ICUs.

To determine whether ICU surrogates with "insecure" psychologic attachment orientations are more prone to requesting tracheostomy and gastrostomy (i.e., life-sustaining therapy) for severe acute brain injury patients with poor prognosis compared to surrogates with "secure" orientations. DESIGN: Cross-sectional survey from November 2017 to August 2018. SETTING: Single neuroscience ICU at an academic medical center. SUBJECTS: Consecutive sample of surrogates of patients admitted to the ICU with a minimum length of stay of 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified surrogates' psychologic attachment orientation via a standard tool, the Relationship Questionnaire, and collected other surrogate and patient demographics. We also presented surrogates with a hypothetical scenario of an intubated severe acute brain injury patient with poor prognosis and asked each surrogate whether he or she would request life-sustaining therapy or comfort measures only. Fisher exact test was used to compare frequency of life-sustaining therapy selection between secure and insecure surrogates. Additionally, we conducted univariate and multivariate analyses to determine other independent predictors of life-sustaining therapy selection. Two-hundred seventy-five of 713 (38.6%) eligible respondents participated; 153 (55.6%) surrogates were secure, and 122 (44.4%) insecure. There was no significant difference in the proportion of secure respondents selecting life-sustaining therapy compared to insecure (18.3% vs 20.5%; p = 0.38). Although still nonsignificant, the observed difference was slightly greater for those with a specific "anxious" insecure subtype versus "nonanxious" (18.2% vs 23.0%; p = 0.41). Overall, a higher proportion of respondents selecting life-sustaining therapy (vs comfort measures only) reported feeling uncertain or very uncertain about the hypothetical decision (45.3% vs 9.5%; p < 0.001). In a multivariate model, nonwhite race and high religiosity were significant predictors of life-sustaining therapy selection. CONCLUSIONS: Although surrogate attachment orientation is not predictive of life-sustaining therapy selection, nonwhite race and high religiosity are. Future interventions designed to support severe acute brain injury surrogates could focus on surrogates prone to selecting life-sustaining therapy with high degrees of uncertainty.

Vitamin B12 and folic acid alleviate symptoms of nutritional deficiency by antagonizing aryl hydrocarbon receptor.

Despite broad appreciation of their clinical utility, it has been unclear how vitamin B12 and folic acid (FA) function at the molecular level to directly prevent their hallmark symptoms of deficiency like anemia or birth defects. To this point, B12 and FA have largely been studied as cofactors for enzymes in the one-carbon (1C) cycle in facilitating the de novo generation of nucleotides and methylation of DNA and protein. Here, we report that B12 and FA function as natural antagonists of aryl hydrocarbon receptor (AhR). Our studies indicate that B12 and FA bind AhR directly as competitive antagonists, blocking AhR nuclear localization, XRE binding, and target gene induction mediated by AhR agonists like 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and 6-formylindolo[3,2-b]carbazole (FICZ). In mice, TCDD treatment replicated many of the hallmark symptoms of B12/FA deficiency and cotreatment with aryl hydrocarbon portions of B12/FA rescued mice from these toxic effects. Moreover, we found that B12/FA deficiency in mice induces AhR transcriptional activity and accumulation of erythroid progenitors and that it may do so in an AhR-dependent fashion. Consistent with these results, we observed that human cancer samples with deficient B12/FA uptake demonstrated higher transcription of AhR target genes and lower transcription of pathways implicated in birth defects. In contrast, there was no significant difference observed between samples with mutated and intact 1C cycle proteins. Thus, we propose a model in which B12 and FA blunt the effect of natural AhR agonists at baseline to prevent the symptoms that arise with AhR overactivation.

Metabolomic profiling of maternal hair suggests rapid development of intrahepatic cholestasis of pregnancy.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms. OBJECTIVE: Investigate the maternal hair metabolome for predictive biomarkers of ICP. METHODS: The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography-mass spectrometry. RESULTS: Of 105 metabolites detected in hair, none were significantly associated with ICP. CONCLUSION: Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.

Structural Insights into Anthranilate Priming during Type II Polyketide Biosynthesis.

The incorporation of nonacetate starter units during type II polyketide biosynthesis helps diversify natural products. Currently, there are few enzymatic strategies for the incorporation of nonacetate starter units in type II polyketide synthase (PKS) pathways. Here we report the crystal structure of AuaEII, the anthranilate:CoA ligase responsible for the generation of anthraniloyl-CoA, which is used as a starter unit by a type II PKS in aurachin biosynthesis. We present structural and protein sequence comparisons to other aryl:CoA ligases. We also compare the AuaEII crystal structure to a model of a CoA ligase homologue, AuaE, which is present in the same gene cluster. AuaE is predicted to have the same fold as AuaEII, but instead of CoA ligation, AuaE catalyzes acyl transfer of anthranilate from anthraniloyl-CoA to the acyl carrier protein (ACP). Together, this work provides insight into the molecular basis for starter unit selection of anthranilate in type II PKS biosynthesis.