Studying the post-COVID-19 condition: research challenges, strategies, and importance of Core Outcome Set development.

BACKGROUND: A substantial portion of people with COVID-19 subsequently experience lasting symptoms including fatigue, shortness of breath, and neurological complaints such as cognitive dysfunction many months after acute infection. Emerging evidence suggests that this condition, commonly referred to as long COVID but also known as post-acute sequelae of SARS-CoV-2 infection (PASC) or post-COVID-19 condition, could become a significant global health burden. MAIN TEXT: While the number of studies investigating the post-COVID-19 condition is increasing, there is no agreement on how this new disease should be defined and diagnosed in clinical practice and what relevant outcomes to measure. There is an urgent need to optimise and standardise outcome measures for this important patient group both for clinical services and for research and to allow comparing and pooling of data. CONCLUSIONS: A Core Outcome Set for post-COVID-19 condition should be developed in the shortest time frame possible, for improvement in data quality, harmonisation, and comparability between different geographical locations. We call for a global initiative, involving all relevant partners, including, but not limited to, healthcare professionals, researchers, methodologists, patients, and caregivers. We urge coordinated actions aiming to develop a Core Outcome Set (COS) for post-COVID-19 condition in both the adult and paediatric populations.

Perceived barriers to early goal-directed mobility in the intensive care unit: Results of a quality improvement evaluation.

BACKGROUND: A multicentre randomised trial demonstrated improved outcomes for intensive care unit (ICU) patients using early, goal-directed mobility implemented by nurses. OBJECTIVES: The aim of the study was to evaluate barriers to nursing mobility, using a validated survey, during an ongoing quality improvement (QI) project (2019) in a medical ICU and determine changes from the pre-QI (2017) baseline. METHODS: Nurses, nurse practitioners, physician assistants, and clinical technicians completed the 26-item Patient Mobilization Attitudes and Beliefs Survey for the ICU (PMABS-ICU). An overall score and three subscale scores (knowledge, attitudes, behaviour), each ranging from 0 to 100, were calculated; higher scores indicated greater barriers. RESULTS: Seventy-five (93% response rate) nurses, eight (100%) nurse practitioners and physician assistants, and 11 (100%) clinical technicians completed the PMABS-ICU. For all respondents (N = 94), the mean (standard deviation) overall PMABS-ICU score was 32 (8) and the knowledge, attitudes and behaviour subscale scores were 22 (11), 33 (11), and 34 (8), respectively. Among all respondents completing the survey in both 2017 and 2019 (N = 46), there was improvement in the mean (95% confidence interval) overall score [-3.1 (-5.8, -0.5); p = .022] and in the knowledge [-5.1 (-8.9, -1.3); p = .010] and attitudes [-3.9 (-7.3, -0.6); p = .023] subscale scores. Among all respondents (N = 48) taking the PMABS-ICU for the first time in 2019 compared with those taking the survey before the QI project in 2017 (N = 99), there was improvement in the mean (95% confidence interval) overall score [-3.8 (-6.5, -1.1); p = .007] and in the knowledge [-6.9 (-11.0, -2.7); p = .001] and attitude [-4.3 (-8.1, -0.5); p = .027] subscale scores. CONCLUSIONS: Using a validated survey administered to ICU nurses and other staff, before and during a structured QI project, there was a decrease in perceived barriers to mobility. Reduced barriers among those taking the survey for the first time during the QI project compared with those taking the survey before the QI project suggests a positive culture change supporting early, goal-directed mobility implemented by nurses.

Provider-Documented Anxiety in the ICU: Prevalence, Risk Factors, and Associated Patient Outcomes.

PURPOSE: To determine the prevalence of provider-documented anxiety in critically ill patients, associated risk factors, and related patient outcomes. METHOD: Chart review of 100 randomly sampled, adult patients, with a length of stay ≥48 hours in a medical or trauma/surgical intensive care unit (ICU). Provider-documented anxiety was identified based on a comprehensive retrospective chart review of the ICU stay, searching for any acute episode of anxiety (e.g., documented words related to anxiety, panic, and/or distress). RESULTS: Of 100 patients, 45% (95% confidence interval: 35%-55%) had documented anxiety, with similar prevalence in medical vs. trauma/surgical ICU. Patients with documented anxiety more frequently had history of anxiety (22% vs. 4%, p = .004) and substance abuse (40% vs. 22%, p = .048). In the ICU, they had greater severity of illness (median (IQR) Acute Physiology Score 16(13,21) vs. 13(8,19), p = .018), screened positive for delirium at least once during ICU stay, (62% vs. 31%, p = .002), benzodiazepines and antipsychotics use (87% vs. 58%, p = .002; 33% vs. 13%, p = .013, respectively), and mental health consultation (31% vs. 18%, p = .132). These patients also had longer ICU and hospital lengths of stay (6(4,11) vs. 4(3,6), p<.001 and 18(10,30) vs. 10(6,16) days, p<.001, respectively) and less frequent discharge back to home (27% vs. 44%, p = .079). CONCLUSIONS: Documented anxiety, occurring in almost half of ICU patients with length of stay ≥48 hours, was associated with a history of anxiety and/or substance abuse, and greater ICU severity of illness, delirium, psychiatric medications, and length of stay. Increased awareness along with more standardized protocols for assessment of anxiety in the ICU, as well as greater evaluation of non-pharmacological treatments for anxiety symptoms in the ICU are warranted.

COVID-19 survivorship: How otolaryngologist-head and neck surgeons can restore quality of life after critical illness.

Mortality from COVID-19 has obscured a subtler crisis - the swelling ranks of COVID-19 survivors. After critical illness, patients often suffer post-intensive care syndrome (PICS), which encompasses physical, cognitive, and/or mental health impairments that are often long-lasting barriers to resuming a meaningful life. Some deficits after COVID-19 critical illness will require otolaryngologic expertise for years after hospital discharge. There are roles for all subspecialties in preventing, diagnosing, or treating sequelae of COVID-19. Otolaryngologist leadership in multidisciplinary efforts ensures coordinated care. Timely tracheostomy, when indicated, may shorten the course of intensive care unit stay and thereby potentially reduce the impairments associated with PICS. Otolaryngologists can provide expertise in olfactory disorders; thrombotic sequelae of hearing loss and vertigo; and laryngotracheal injuries that impair speech, voice, swallowing, communication, and breathing. In the aftermath of severe COVID-19, otolaryngologists are poised to lead efforts in early identification and intervention for impairments affecting patients' quality of life.

Correction to: Screening for posttraumatic stress disorder in ARDS survivors: validation of the impact of event Scale-6 (IES-6).

In the publication of this article [1], there is an error in the Abstract. This has now been included in this correction article.

Perceived Barriers to Mobility in a Medical ICU: The Patient Mobilization Attitudes & Beliefs Survey for the ICU.

PURPOSE: Early mobilization in the intensive care unit (ICU) can improve patient outcomes but has perceived barriers to implementation. As part of an ongoing structured quality improvement project to increase mobilization of medical ICU patients by nurses and clinical technicians, we adapted the existing, validated Patient Mobilization Attitudes & Beliefs Survey (PMABS) for the ICU setting and evaluated its performance characteristics and results. MATERIALS AND METHODS: The 26-item PMABS adapted for the ICU (PMABS-ICU) was administered as an online survey to 163 nurses, clinical technicians, respiratory therapists, attending and fellow physicians, nurse practitioners, and physician assistants in one medical ICU. We evaluated the overall and subscale (knowledge, attitude, and behavior) scores and compared these scores by respondent characteristics (clinical role and years of work experience). RESULTS: The survey response rate was 96% (155/163). The survey demonstrated acceptable discriminant validity and acceptable internal consistency for the overall scale (Cronbach α: 0.82, 95% confidence interval: 0.76-0.85), with weaker internal consistency for all subscales (Cronbach α: 0.62-0.69). Across all respondent groups, the overall barrier score (range: 1-100) was relatively low, with attending physicians perceiving the lowest barriers (median [interquartile range]: 30 [28-34]) and nurses perceiving the highest (37 [31-40]). Within the first 10 years of work experience, greater experience was associated with a lower overall barrier score (-0.8 for each additional year; P = 0.02). CONCLUSIONS: In our medical ICU, across 6 different clinical roles, there were relatively low perceived barriers to patient mobility, with greater work experience over the first 10 years being associated with lower perceived barriers. As part of a structured quality improvement project, the PMABS-ICU may be valuable in assisting to identify specific perceived barriers for consideration in designing mobility interventions for the ICU setting.

Derivation of cancer no significant risk levels and screening safety assessment for 2-nitropropane in spray products.

Two proposition 65 no-significant-risk level (NSRL)-type values were derived for 2-nitropropane (2-NP), in the absence of a Californian published NSRL. In addition, a safety assessment was performed based on estimated typical consumer inhalation and dermal exposure to 2-NP during indoor application of paint from a spray can containing the solvent 1-nitropropane. For the NSRL derivation, benchmark dose (BMD) modeling was performed using hepatocellular carcinoma incidence data from 2-NP single exposure inhalation studies in Sprague-Dawley rats. Several BMD models provided an acceptable fit for the male rat hepatocellular carcinoma incidence data (gamma, log-probit, log-logistic and multistage); therefore, the mean of the BMD lower limits from each model were used as the point of departure to derive the inhalation cancer potency. The oral human cancer potency was derived from the inhalation human cancer potency based on the ratio of the uptake factors for inhalation vs. oral routes. The derived inhalation and oral NSRLs are 67 µg/day and 32 µg/day, respectively. For the inhalation and dermal exposure assessment, three key factors were analyzed: the 2-NP residual concentration in the spray paint product, the mass of spray paint used and the frequency of use. Based on the screening exposure assessment, potential consumer inhalation and dermal exposure to 2-NP from indoor application of paint from a spray can does not exceed our proposed NSRLs, and a warning label is therefore not required for spray can products containing the solvent 1-nitropropane where 2-NP is a minor contaminant.

Usability and acceptability of a mobile application prototype for a combined behavioural activation and physical rehabilitation intervention in acute respiratory failure survivors.

BACKGROUND: Acute respiratory failure survivors experience depression symptoms and new impairments in physical function. Behavioural activation, an evidence-based nonpharmacological treatment for depression, combined with physical rehabilitation, is a promising intervention. Notably, mHealth applications (Apps) are potentially effective methods of delivering home-based interventions. OBJECTIVES: The objective of this study was to evaluate the usability and acceptability of a prototype App to deliver a combined, home-based behavioural activation and rehabilitation intervention to acute respiratory failure survivors. METHODS: A prospective user-preference study was conducted with acute respiratory failure survivors and self-designated care partners. Survivors were adults with at least mild depression symptoms before hospital discharge who received mechanical ventilation in the intensive care unit for ≥24 h. Survivors and care partners reviewed the App during a single in-person home visit and completed the System Usability Scale (range: 0-100; score >73 considered "good") and a semistructured interview. RESULTS: Ten patient/care partner dyads completed study. The median [interquartile range] patient age was 50 [40-64] years, and 50% were female. The median System Usability Scale scores among patients and care partners were 76 [68-83] and 88 [75-94], respectively. Qualitative feedback supported usability and acceptability of the App, with three themes reported: (1) stigma associated with depression, (2) App as a motivator for recovery, and (3) App providing multidisciplinary support for survivor and care partner. CONCLUSIONS: A mobile App prototype designed to deliver a combined behavioural activation and rehabilitation intervention was usable and acceptable to survivors of acute respiratory failure and their care partners. Given the reported stigma associated with depression, the self-directed App may be particularly valuable for motivation and multidisciplinary support.

Screening for posttraumatic stress disorder in ARDS survivors: validation of the Impact of Event Scale-6 (IES-6).

BACKGROUND: Posttraumatic stress disorder (PTSD) symptoms are common in acute respiratory distress syndrome (ARDS) survivors. Brief screening instruments are needed for clinical and research purposes. We evaluated internal consistency, external construct, and criterion validity of the Impact of Event Scale-6 (IES-6; 6 items) compared to the original Impact of Event Scale-Revised (IES-R; 22 items) and to the Clinician Administered PTSD Scale (CAPS) reference standard evaluation in ARDS survivors. METHODS: This study is a secondary analysis from two independent multi-site, prospective studies of ARDS survivors. Measures of internal consistency, and external construct and criterion validity were evaluated. RESULTS: A total of 1001 ARDS survivors (51% female, 76% white, mean (SD) age 49 (14) years) were evaluated. The IES-6 demonstrated internal consistency over multiple time points up to 5 years after ARDS (Cronbach's alpha = 0.86 to 0.91) and high correlation with the IES-R (0.96; 95% confidence interval (CI): 0.94 to 0.97). The IES-6 demonstrated stronger correlations with related constructs (e.g., anxiety and depression; |r| = 0.32 to 0.52) and weaker correlations with unrelated constructs (e.g., physical function and healthcare utilization measures (|r| = 0.02 to 0.27). Criterion validity evaluation with the CAPS diagnosis of PTSD in a subsample of 60 participants yielded an area under receiver operating characteristic curve (95% CI) of 0.93 (0.86, 1.00), with an IES-6 cutoff score of 1.75 yielding 0.88 sensitivity and 0.85 specificity. CONCLUSIONS: The IES-6 is reliable and valid for screening for PTSD in ARDS survivors and may be useful in clinical and research settings.

Perspectives of survivors, families and researchers on key outcomes for research in acute respiratory failure.

BACKGROUND: There is heterogeneity among the outcomes evaluated in studies of survivors of acute respiratory failure (ARF). AIM: To evaluate the importance of specific outcome domains to acute respiratory distress syndrome (ARDS) survivors, their family members and clinical researchers. METHODS: Nineteen outcome domains were identified from the National Institutes of Health's Patient Reported Outcomes Measurement Information System; WHO's International Classification of Functioning, Disability, and Health; Society of Critical Care Medicine's Post-Intensive Care Syndrome (PICS); as well as patient, clinician and researcher input. We surveyed ARDS survivors, family members and critical care researchers, 279 respondents in total, using a 5-point scale (strongly disagree, disagree, neutral, agree and strongly agree) to rate the importance of measuring each domain in studies of ARF survivors' postdischarge outcomes. MEASUREMENTS AND MAIN RESULTS: At least 80% of patients and family members supported (ie, rated 'agree' or 'strongly agree') that 15 of the 19 domains should be measured in all future studies. Among researchers, 6 of 19 domains were supported, with researchers less supportive for all domains, except survival (95% vs 72% support). Overall, four domains were supported by all groups: physical function, cognitive function, return to work or prior activities and mental health. CONCLUSION: Patient, family and researcher groups supported inclusion of outcome domains that fit within the PICS framework. Patients and family members also supported many additional domains, emphasising the importance of including patients/family, along with researchers, in consensus processes to select core outcome domains for future research studies.

Benchmark dose (BMD) modeling: current practice, issues, and challenges.

Benchmark dose (BMD) modeling is now the state of the science for determining the point of departure for risk assessment. Key advantages include the fact that the modeling takes account of all of the data for a particular effect from a particular experiment, increased consistency, and better accounting for statistical uncertainties. Despite these strong advantages, disagreements remain as to several specific aspects of the modeling, including differences in the recommendations of the US Environmental Protection Agency (US EPA) and the European Food Safety Authority (EFSA). Differences exist in the choice of the benchmark response (BMR) for continuous data, the use of unrestricted models, and the mathematical models used; these can lead to differences in the final BMDL. It is important to take confidence in the model into account in choosing the BMDL, rather than simply choosing the lowest value. The field is moving in the direction of model averaging, which will avoid many of the challenges of choosing a single best model when the underlying biology does not suggest one, but additional research would be useful into methods of incorporating biological considerations into the weights used in the averaging. Additional research is also needed regarding the interplay between the BMR and the UF to ensure appropriate use for studies supporting a lower BMR than default values, such as for epidemiology data. Addressing these issues will aid in harmonizing methods and moving the field of risk assessment forward.

Cleaning and asthma: A systematic review and approach for effective safety assessment.

Research indicates a correlative relationship between asthma and use of consumer cleaning products. We conduct a systematic review of epidemiological literature on persons who use or are exposed to cleaning products, both in occupational and domestic settings, and risk of asthma or asthma-like symptoms to improve understanding of the causal relationship between exposure and asthma. A scoring method for assessing study reliability is presented. Although research indicates an association between asthma and the use of cleaning products, no study robustly investigates exposure to cleaning products or ingredients along with asthma risk. This limits determination of causal relationships between asthma and specific products or ingredients in chemical safety assessment. These limitations, and a lack of robust animal models for toxicological assessment of asthma, create the need for a weight-of-evidence (WoE) approach to examine an ingredient or product's asthmatic potential. This proposed WoE method organizes diverse lines of data (i.e., asthma, sensitization, and irritation information) through a systematic, hierarchical framework that provides qualitatively categorized conclusions using hazard bands to predict a specific product or ingredient's potential for asthma induction. This work provides a method for prioritizing chemicals as a first step for quantitative and scenario-specific safety assessments based on their potential for inducing asthmatic effects. Acetic acid is used as a case study to test this framework.

Psychiatric Symptoms in Acute Respiratory Distress Syndrome Survivors: A 1-Year National Multicenter Study.

OBJECTIVE: To evaluate prevalence, severity, and co-occurrence of and risk factors for depression, anxiety, and posttraumatic stress disorder symptoms over the first year after acute respiratory distress syndrome. DESIGN: Prospective longitudinal cohort study. SETTINGS: Forty-one Acute Respiratory Distress Syndrome Network hospitals across the United States. PATIENTS: Six hundred ninety-eight acute respiratory distress syndrome survivors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Psychiatric symptoms were evaluated by using the Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised at 6 and 12 months. Adjusted prevalence ratios for substantial symptoms (binary outcome) and severity scores were calculated by using Poisson and linear regression, respectively. During 12 months, a total of 416 of 629 patients (66%) with at least one psychiatric outcome measure had substantial symptoms in at least one domain. There was a high and almost identical prevalence of substantial symptoms (36%, 42%, and 24% for depression, anxiety, and posttraumatic stress disorder) at 6 and 12 months. The most common pattern of co-occurrence was having symptoms of all three psychiatric domains simultaneously. Younger age, female sex, unemployment, alcohol misuse, and greater opioid use in the ICU were significantly associated with psychiatric symptoms, whereas greater severity of illness and ICU length of stay were not associated. CONCLUSIONS: Psychiatric symptoms occurred in two thirds of acute respiratory distress syndrome survivors with frequent co-occurrence. Sociodemographic characteristics and in-ICU opioid administration, rather than traditional measures of critical illness severity, should be considered in identifying the patients at highest risk for psychiatric symptoms during recovery. Given high co-occurrence, acute respiratory distress syndrome survivors should be simultaneously evaluated for a full spectrum of psychiatric sequelae to maximize recovery.

Early Psychological Therapy in Critical Illness.

Survivors of critical illness often experience long-lasting impairments in mental, cognitive, and physical functioning. Acute stress reactions and delusional memories appear to play an important role in psychological morbidity following critical illness, and few interventions exist to address these symptoms. This review elucidates acute psychological stressors experienced by the critically ill. The effects of psychological stress and state of mind on disease are discussed using examples from the non-intensive care unit (ICU) literature, including a review of placebo and nocebo effects. After reviewing the effect of the mind on both psychological and physiological outcomes, we then focus on the role of memories-including their malleable nature and the consequences of false memories. Memory may play a role in the genesis of subsequent psychological trauma. Traumatic memories may begin forming even before the patient arrives in the ICU and during their state of unconsciousness in the ICU. Hence, practical interventions for redirecting patients' thoughts, such as positive suggestion techniques and actively involving patients in the treatment process as early as possible, are worthy of further investigation.

Posttraumatic stress disorder in critical illness survivors: a metaanalysis.

OBJECTIVE: To conduct a systematic review and metaanalysis of the prevalence, risk factors, and prevention/treatment strategies for posttraumatic stress disorder symptoms in critical illness survivors. DATA SOURCES: PubMed, Embase, CINAHL, PsycINFO, and Cochrane Library from inception through March 5, 2014. STUDY SELECTION: Eligible studies met the following criteria: 1) adult general/nonspecialty ICU, 2) validated posttraumatic stress disorder instrument greater than or equal to 1 month post-ICU, and 3) sample size greater than or equal to 10 patients. DATA EXTRACTION: Duplicate independent review and data abstraction from all eligible titles/abstracts/full-text articles. DATA SYNTHESIS: The search identified 2,817 titles/abstracts, with 40 eligible articles on 36 unique cohorts (n = 4,260 patients). The Impact of Event Scale was the most common posttraumatic stress disorder instrument. Between 1 and 6 months post-ICU (six studies; n = 456), the pooled mean (95% CI) Impact of Event Scale score was 20 (17-24), and the pooled prevalences of clinically important posttraumatic stress disorder symptoms (95% CI) were 25% (18-34%) and 44% (36-52%) using Impact of Event Scale thresholds greater than or equal to 35 and greater than or equal to 20, respectively. Between 7 and 12 months post-ICU (five studies; n = 698), the pooled mean Impact of Event Scale score was 17 (9-24), and pooled prevalences of posttraumatic stress disorder symptoms were 17% (10-26%) and 34% (22-50%), respectively. ICU risk factors for posttraumatic stress disorder symptoms included benzodiazepine administration and post-ICU memories of frightening ICU experiences. Posttraumatic stress disorder symptoms were associated with worse quality of life. In European-based studies: 1) an ICU diary was associated with a significant reduction in posttraumatic stress disorder symptoms, 2) a self-help rehabilitation manual was associated with significant posttraumatic stress disorder symptom reduction at 2 months, but not 6 months; and 3) a nurse-led ICU follow-up clinic did not reduce posttraumatic stress disorder symptoms. CONCLUSIONS: Clinically important posttraumatic stress disorder symptoms occurred in one fifth of critical illness survivors at 1-year follow-up, with higher prevalence in those who had comorbid psychopathology, received benzodiazepines, and had early memories of frightening ICU experiences. In European studies, ICU diaries reduced posttraumatic stress disorder symptoms.

A tiered asthma hazard characterization and exposure assessment approach for evaluation of consumer product ingredients.

Asthma is a complex syndrome with significant consequences for those affected. The number of individuals affected is growing, although the reasons for the increase are uncertain. Ensuring the effective management of potential exposures follows from substantial evidence that exposure to some chemicals can increase the likelihood of asthma responses. We have developed a safety assessment approach tailored to the screening of asthma risks from residential consumer product ingredients as a proactive risk management tool. Several key features of the proposed approach advance the assessment resources often used for asthma issues. First, a quantitative health benchmark for asthma or related endpoints (irritation and sensitization) is provided that extends qualitative hazard classification methods. Second, a parallel structure is employed to include dose-response methods for asthma endpoints and methods for scenario specific exposure estimation. The two parallel tracks are integrated in a risk characterization step. Third, a tiered assessment structure is provided to accommodate different amounts of data for both the dose-response assessment (i.e., use of existing benchmarks, hazard banding, or the threshold of toxicological concern) and exposure estimation (i.e., use of empirical data, model estimates, or exposure categories). Tools building from traditional methods and resources have been adapted to address specific issues pertinent to asthma toxicology (e.g., mode-of-action and dose-response features) and the nature of residential consumer product use scenarios (e.g., product use patterns and exposure durations). A case study for acetic acid as used in various sentinel products and residential cleaning scenarios was developed to test the safety assessment methodology. In particular, the results were used to refine and verify relationships among tiered approaches such that each lower data tier in the approach provides a similar or greater margin of safety for a given scenario.