Feasibility and acceptability of conducting a partially randomised controlled trial examining interventions to improve psychological health after discharge from the intensive care unit.

BACKGROUND: Interventions to support psychological recovery after critical illness, including information provision via an intensive care unit (ICU) diary or discharge summary, have been widely adopted in some regions, albeit without strong empirical evidence. OBJECTIVE: The objective of this study was to examine the feasibility and acceptability, for patients, family members, and clinicians, of information provision via an ICU diary or discharge summary to support psychological recovery for critical illness survivors. METHODS: This was a pilot, partially randomised patient preference study in a mixed ICU in a tertiary hospital in Australia. Eligible patients were those in the ICU for >24 h and who were able to converse in English. Interventions were ICU diary or discharge summary compared with usual care. Feasibility was assessed throughout the study process, and acceptability assessed 3 and 6 months after hospital discharge, with data analysed descriptively and thematically. RESULTS: Sixty-one patients were recruited; 45 completed 3-month follow-up (74%), and 37 (61%), 6-month follow-up. Participants were medical (39%), surgical (30%), and trauma (31%) patients; aged 55 [interquartile range (IQR): 36-67] years; and stayed in the ICU for 7 [IQR: 3-13] days and hospital for 23 [IQR: 14-32] days. Within the partially randomised framework, 34 patients chose their intervention - four chose usual care, 10 ICU diary, and 20 discharge summary. The remaining 27 patients were randomised - nine usual care, 10 ICU diary, and seven discharge summary. The majority (>90%) considered each intervention helpful during recovery; however, a significant proportion of patients reported distress associated with reading the ICU diary (42%) or discharge summary (15%). Clinicians reported they were hesitant to make diary entries. CONCLUSIONS: When given a choice, more patients chose a discharge summary over the ICU diary or usual care. Participants considered both interventions acceptable. Given the reports of distress associated with information provision, clear empirical evidence is required to determine effectiveness, optimal timing, support needed, and for whom they should be used. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12615001079538.

Trait Anxiety But Not State Anxiety During Critical Illness Was Associated With Anxiety and Depression Over 6 Months After ICU.

OBJECTIVE: To determine the association between anxiety during critical illness and symptoms of anxiety and depression over 6 months after ICU discharge in survivors of intensive care treatment. DESIGN: Longitudinal study. SETTING: One closed mixed ICU in an adult tertiary hospital in Brisbane, Australia. PATIENTS: Participants (n = 141) were adults (≥ 8 yr), admitted to ICU for at least 24 hours, able to communicate either verbally or nonverbally, understand English, and open their eyes spontaneously or in response to voice. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The outcomes of symptoms of anxiety and depression over 6 months after ICU discharge were assessed using the Hospital Anxiety Depression Scale. The primary variable of interest was anxiety during critical illness. Two components of anxiety (state and trait) were assessed during critical illness using the Faces Anxiety Scale and the trait component of the State-Trait Anxiety Inventory. Perceived social support, cognitive functioning, and posttraumatic stress symptoms were also assessed using standardized instruments. Clinical and demographic data were obtained from patients and medical records. Participants were followed up in hospital wards and at 3 and 6 months after ICU discharge. During ICU treatment, 81 of the 141 participants (57%) reported moderate to severe levels of state anxiety. Of the 92 participants who completed the surveys at the 6-month follow-up, 26 participants (28%) reported symptoms of anxiety and 21 (23%) symptoms of depression. Symptoms of anxiety and depression were strongly correlated in this cohort of survivors. Trait anxiety was significantly associated with both anxiety and depression symptoms over time; however, state anxiety was not associated with either outcome. Participants who reported post-ICU memories of intra-ICU anxiety were significantly more anxious during recovery over 6 months. Cognitive functioning and posttraumatic stress symptoms were both significantly associated with anxiety and depression symptoms over time. CONCLUSION: Symptoms of anxiety and depression are a significant issue for general ICU survivors. Trait anxiety was significantly associated with adverse emotional outcomes over 6 months after ICU discharge. There was also a significant relationship between post-ICU memories of intra-ICU anxiety and anxiety during recovery. Interventions to reduce anxiety during critical illness need to be considered and evaluated for their longer term benefits for survivors of critical illness.

In ICU state anxiety is not associated with posttraumatic stress symptoms over six months after ICU discharge: A prospective study.

BACKGROUND: Posttraumatic stress symptoms are common after intensive care treatment. The influence of anxiety during critical illness on the development of posttraumatic stress symptoms needs to be investigated. OBJECTIVE: To determine the association between anxiety during critical illness (state and trait components) and posttraumatic stress symptoms over six months after ICU discharge. METHODS: Prospective study including 141 patients admitted ≥24h to a closed mixed adult ICU in a tertiary hospital. State anxiety was assessed with the Faces Anxiety Scale during ICU stay. Trait anxiety was measured with the State-Trait Anxiety Inventory Form Y-2. Posttraumatic stress symptoms were measured at three and six months after ICU discharge using the Post-Traumatic Stress Symptoms 10-Question Inventory. Clinical and demographical data were also collected. Mixed effect regression models were used to determine if state and trait anxiety were factors significantly associated with posttraumatic stress symptoms over time. RESULTS: Moderate to severe levels of state anxiety in ICU were reported by 81 (57%) participants. Levels of trait anxiety (median 36 IQR: 29-47) were similar to the Australian population. High levels of posttraumatic stress symptoms occurred at three (n=19, 19%) and six months (n=15, 17%). Factors independently associated with posttraumatic stress symptoms were trait anxiety (2.2; 95% CI, 0.3-4.1; p=0.02), symptoms of anxiety after ICU discharge (0.6; 95% CI, 0.2-1.1; p=0.005), younger age (-1.4; 95% CI, -2.6 to -0.2; p=0.02) and evidence of mental health treatment prior to the ICU admission (5.2; 95% CI, 1.5-8.9; p=0.006). CONCLUSIONS: Posttraumatic stress symptoms occurred in a significant proportion of ICU survivors and were significantly associated with higher levels of trait anxiety, younger age, mental health treatment prior to the ICU admission and more symptoms of anxiety after ICU discharge. Early assessment and interventions directed to reduce state and trait anxiety in ICU survivors may be of benefit.

What is the relationship between elements of ICU treatment and memories after discharge in adult ICU survivors?

OBJECTIVES: Patients admitted to an intensive care unit (ICU) often experience distressing memories during recovery that have been associated with poor psychological and cognitive outcomes. The aim of this literature review was to synthesise the literature reporting on relationships between elements of ICU treatment and memories after discharge in adult ICU survivors. REVIEW METHOD USED: Integrative review methods were used to systematically search, select, extract, appraise and summarise current knowledge from the available research and identify gaps in the literature. DATA SOURCES: The following electronic databases were systematically searched: PubMed, Ovid EMBASE, EBSCOhost CINAHL, PsycINFO and Cochrane Central Register of Controlled Trials. Additional studies were identified through searches of bibliographies. Original quantitative research articles written in English that were published in peer-review journals were included. REVIEW METHODS: Data extracted from studies included authors, study aims, population, sample size and characteristics, methods, ICU treatments, ICU memory definitions, data collection strategies and findings. Study quality assessment was based on elements of the Critical Appraisal Skills Programme using the checklists developed for randomised controlled trials and cohort studies. RESULTS: Fourteen articles containing data from 13 studies met the inclusion criteria and were included in the final analysis. The relatively limited evidence about the association between elements of ICU treatment and memories after ICU discharge suggest that deep sedation, corticoids and administration of glucose 50% due to hypoglycaemia contribute to the development of delusional memories and amnesia of ICU stay. CONCLUSIONS: The body of literature on the relationship between elements of ICU treatment and memories after ICU discharge is small and at its early stages. Larger studies using rigorous study design are needed in order to evaluate the effects of different elements of ICU treatment on the development of memories of the ICU during recovery.

Study protocol: Intensive Care Anxiety and Emotional Recovery (Icare)-a prospective study.

BACKGROUND: Survivors of intensive care units (ICUs) commonly present with symptoms of anxiety, depression and post-traumatic stress disorder (PTSD) during recovery. A number of factors have been identified as predictors of these adverse emotional outcomes, but the role of state anxiety during critical illness in the development of these emotional problems remains unknown. PURPOSE: The Intensive Care Anxiety and Emotional Recovery (ICARe) study protocol proposes the development of a statistical model to determine the relationship between state anxiety during ICU stay and symptoms of anxiety, depression and PTSD at three occasions; after ICU discharge but prior to hospital discharge and at the third and sixth months post ICU discharge. METHODS: Prospective study including adult patients admitted to the ICU of a tertiary metropolitan Australian hospital for ≥24 h who are able to: (1) communicate verbally or nonverbally; (2) understand English and (3) open their eyes spontaneously or in response to voice to respond to the Faces Anxiety Scale (state anxiety assessment). One hundred and seventy patients will be assessed for their levels of state anxiety during their ICU stay to achieve a sample size of about 104 patients six months after discharge. The outcomes of the ICARe study will include symptoms of anxiety, depression and PTSD assessed by standardised questionnaires widely used in intensive care research. Demographic, clinical, and social support information will also be collected. RESULTS: The projected sample size will provide sufficient power to evaluate the association between state anxiety and adverse emotional outcomes, as well as a variety of variables that will be entered into a multivariate regression analysis. CONCLUSION: This study will provide new evidence to improve care during critical illness and reduce adverse outcomes during recovery with the potential to decrease unnecessary suffering, promote comfort and improve long-term recovery.

Cellular stress modulates severity of the inflammatory response in lungs via cell surface BiP.

Inflammation is a central pathogenic feature of the acute respiratory distress syndrome (ARDS) in COVID-19. Previous pathologies such as diabetes, autoimmune or cardiovascular diseases become risk factors for the severe hyperinflammatory syndrome. A common feature among these risk factors is the subclinical presence of cellular stress, a finding that has gained attention after the discovery that BiP (GRP78), a master regulator of stress, participates in the SARS-CoV-2 recognition. Here, we show that BiP serum levels are higher in COVID-19 patients who present certain risk factors. Moreover, early during the infection, BiP levels predict severe pneumonia, supporting the use of BiP as a prognosis biomarker. Using a mouse model of pulmonary inflammation, we observed increased levels of cell surface BiP (cs-BiP) in leukocytes during inflammation. This corresponds with a higher number of neutrophiles, which show naturally high levels of cs-BiP, whereas alveolar macrophages show a higher than usual exposure of BiP in their cell surface. The modulation of cellular stress with the use of a clinically approved drug, 4-PBA, resulted in the amelioration of the lung hyperinflammatory response, supporting the anti-stress therapy as a valid therapeutic strategy for patients developing ARDS. Finally, we identified stress-modulated proteins that shed light into the mechanism underlying the cellular stress-inflammation network in lungs.

EGFR detection in extracellular vesicles of breast cancer patients through immunosensor based on silica-chitosan nanoplatform.

In the present work, we designed a microfluidic electrochemical immunosensor with enough sensibility and precision to quantify epithermal growth factor receptor (EGFR) in plasma extracellular vesicles (EVs) of plasma from breast cancer patients. The sensor employs SiNPs coated with chitosan (SiNPs-CH) as reaction's platform, based on the covalently immobilization of monoclonal anti-EGFR on SiNPs-CH retained in the central channel (CC) of the microfluidic device. The synthetized SiNPs-CH were characterized by UV-visible spectroscopy (UV-visible), energy dispersive spectrometry (EDS), Nanoparticle Tracking Analysis (NTA) and transmission electron microscopy (TEM). EGFR was quantified by a direct sandwich immunoassay measuring through a horseradish peroxidase (HRP)-conjugated anti-EGFR. The enzymatic product (benzoquinone) was detected by reduction at - 100 mV on a sputtering gold electrode. The measured current was directly proportional to the level of EGFR in human serum samples. The linear range was from 0 ng mL-1 to 50 ng mL-1. The detection limit was 1.37 pg mL-1, and the within- and between-assay coefficients of variation were below 6.25%. Finally, plasma samples from 30 early breast cancer patients and 20 healthy donor were analyzed by the novel method. EGFR levels in EVs (EVs-EGFR) were significantly higher than in the healthy control group (p = 0.002) and also, more sensitivity and specificity than normal serum markers like CEA and CA15.3 has been observed. EVs-EGFR concentration correlates with EGFR tumor status (p = 0.0003) as well as it correlate with the tumor size and pathological grade. To conclude, plasma EVs are suitable for proteomic characterization of cancer disease, as long as the employed method has sufficient sensitivity, like the case of immune-electrochemical nanosensors with incremented reaction surface.

Perspectives of patients and family members regarding psychological support using intensive care diaries: An exploratory mixed methods study.

PURPOSE: Diaries summarizing intensive care are routine practice in some countries, although evidence to support diary use is limited. The purpose of this study was to identify whether distress post-intensive care influences patients' and relatives' choice as to whether they would like to receive a diary and what information delivery method is preferred. MATERIALS AND METHODS: Intensive care patients admitted for at least 3 days and their relatives participated in an exploratory mixed methods study. Interviews were conducted 3 to 5 months after discharge. Psychological distress was assessed using Kessler-10 and Posttraumatic Stress Disorder Symptom Checklist - 5. Perceptions of benefit of diaries were assessed using a 4-point Likert scale. Differences were examined using Fisher exact test (P<.05). RESULTS: Fifty-seven patients and 22 relatives consented to participation, with 22 patients and 22 relatives interviewed before data saturation. Psychological distress was evident in 25 (47%) patients and 5 (23%) relatives. Participants' psychological health was similar for those who perceived diaries as beneficial, and those who did not. Themes included memory, process, and impact, although opinions were diverse. CONCLUSIONS: Patient and relative preferences of receiving a diary are not related to psychological distress. Diverse opinions around common themes suggest the need for a range of interventions to aid psychological recovery.

Factors associated with anxiety in critically ill patients: A prospective observational cohort study.

BACKGROUND: Anxiety is an unpleasant emotion that most intensive care patients experience. This emotion is an important issue in intensive care settings because of its prevalence, adverse effects and severity. Little is known about the factors associated with state and trait anxiety during critical illness. OBJECTIVES: To describe the patterns of state anxiety reported by intensive care patients, and identify factors associated with state and trait anxiety. DESIGN: Prospective observational cohort study. SETTINGS: One mixed intensive care unit in Brisbane, Australia. PARTICIPANTS: Adults (n=141, ≥18 years) admitted to the intensive care unit for ≥24h; able to communicate verbally or non-verbally; understand English; and, open their eyes spontaneously or in response to voice. METHODS: Outcomes were state anxiety as measured by the Faces Anxiety Scale and trait anxiety as measured by the State-Trait Anxiety Inventory. Pre-intensive care factors tested for possible associations with both state and trait anxiety were: age, gender, marital status, employment status, level of education, smoking status, personality trait of optimism and evidence of mental health care/treatment. Intra-intensive care factors tested were: reason for admission to the intensive care unit, delirium, pain, airway status, hours of mechanical ventilation, severity of illness, days of stay in intensive care, exposure to corticosteroids, opioids, benzodiazepines, anxiolytics, antidepressants, beta-blockers, anaesthetic agents and analgesics; length of sedation and analgesia and total doses of sedatives and analgesics. RESULTS: Of 141 participants, 98 (70%) were male with an average age of 54 (standard deviation: ±15) years and stayed in intensive care for about 4 (Interquartile Range: 3-7) days. The majority (n=115; 82%) of participants experienced state anxiety at least once during their stay in intensive care, with 57% reporting moderate to severe levels. Factors related to state anxiety in intensive care were pain and trait anxiety. Factors associated with trait anxiety were trait optimism, state anxiety, evidence of mental health care/treatment and age. CONCLUSIONS: This study provides a better understanding of contributing factors for anxiety in the critically ill. Trait anxiety and state anxiety were significantly associated with each other, namely, patients who were anxious by nature experienced higher levels of state anxiety, which persisted throughout their stay in the intensive care unit. Recognising the importance of state and trait anxiety assessments using validated tools and determining ways to manage anxiety in the critically ill are critical aspects of the intensive care nurses role.

Interacting resident epicardium-derived fibroblasts and recruited bone marrow cells form myocardial infarction scar.

BACKGROUND: Although efforts continue to find new therapies to regenerate infarcted heart tissue, knowledge of the cellular and molecular mechanisms involved remains poor. OBJECTIVES: This study sought to identify the origin of cardiac fibroblasts (CFs) in the infarcted heart to better understand the pathophysiology of ventricular remodeling following myocardial infarction (MI). METHODS: Permanent genetic tracing of epicardium-derived cell (EPDC) and bone marrow-derived blood cell (BMC) lineages was established using Cre/LoxP technology. In vivo gene and protein expression studies, as well as in vitro cell culture assays, were developed to characterize EPDC and BMC interaction and properties. RESULTS: EPDCs, which colonize the cardiac interstitium during embryogenesis, massively differentiate into CFs after MI. This response is disease-specific, because angiotensin II-induced pressure overload does not trigger significant EPDC fibroblastic differentiation. The expansion of epicardial-derived CFs follows BMC infiltration into the infarct site; the number of EPDCs equals that of BMCs 1 week post-infarction. BMC-EPDC interaction leads to cell polarization, packing, massive collagen deposition, and scar formation. Moreover, epicardium-derived CFs display stromal properties with respect to BMCs, contributing to the sustained recruitment of circulating cells to the damaged zone and the cardiac persistence of hematopoietic progenitors/stem cells after MI. CONCLUSIONS: EPDCs, but not BMCs, are the main origin of CFs in the ischemic heart. Adult resident EPDC contribution to the CF compartment is time- and disease-dependent. Our findings are relevant to the understanding of post-MI ventricular remodeling and may contribute to the development of new therapies to treat this disease.