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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., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Introduction: As short-term mortality declines for critically ill patients, a growing number of survivors face long-term physical, cognitive and/or mental health impairments. After hospital discharge, many critical illness survivors require an in-depth plan to address their healthcare needs. Early after hospital discharge, numerous survivors experience inadequate care or a mismatch between their healthcare needs and what is provided. Many patients are readmitted to the hospital, have substantial healthcare resource use and experience long-lasting morbidity. The objective of this study is to investigate the gap in healthcare needs occurring immediately after hospital discharge and its association with hospital readmissions or death for survivors of acute respiratory failure (ARF)., Methods and Analysis: In this multicentre prospective cohort study, we will enrol 200 survivors of ARF in the intensive care unit (ICU) who are discharged directly home from their acute care hospital stay. Unmet healthcare needs, the primary exposure of interest, will be evaluated as soon as possible within 1 to 4 weeks after hospital discharge, via a standardised telephone assessment. The primary outcome, death or hospital readmission, will be measured at 3 months after discharge. Secondary outcomes (eg, quality of life, cognitive impairment, depression, anxiety and post-traumatic stress disorder) will be measured as part of 3-month and 6-month telephone-based follow-up assessments. Descriptive statistics will be reported for the exposure and outcome variables along with a propensity score analysis, using inverse probability weighting for the primary exposure, to evaluate the relationship between the primary exposure and outcome., Ethics and Dissemination: The study received ethics approval from Vanderbilt University Medical Center Institutional Review Board (IRB) and the University of Utah IRB (for the Veterans Affairs site). These results will inform both clinical practice and future interventional trials in the field. We plan to disseminate the results in peer-reviewed journals, and via national and international conferences., Trial Registration Details: ClinicalTrials.gov (NCT03738774). Registered before enrollment of the first patient., Competing Interests: Competing interests: Samuel M. Brown reports grants from National Institutes of Health, Department of Defense, Intermountain Research and Medical Foundation, and Janssen and consulting fees paid to his employer from Faron and Sedana, outside the submitted work. He also reports payments for DSMB service from Hamilton, outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Topic: Many patients in intensive care units have frightening experiences and memories and subsequent post-intensive care syndrome, with psychiatric morbidity including depression, anxiety, and posttraumatic stress disorder. Intensive care unit diaries, written by staff members and families, support patients' understanding of what occurred and may alleviate their psychological suffering., Clinical Relevance: An increasing number of critical care nurses in the United States and elsewhere are implementing intensive care unit diaries, but implementation remains challenging., Purpose: To address emerging questions and support implementation in the United States, we held the Third International Intensive Care Unit Diary Conference as a 1-day preconference during the Seventh Annual Johns Hopkins Critical Care Rehabilitation Conference on November 1, 2018, in Baltimore, Maryland. This article summarizes the conference., Content Covered: Conference presentations included intensive care unit-related experiences of patients and families, psychosocial aspects of post-intensive care syndrome, the evolution of diaries, implementation strategies for intensive care unit diaries, special topics (eg, legal issues, electronic vs handwritten diaries, pediatric diaries, and time of handover), and psychosocial recovery., (©2020 American Association of Critical-Care Nurses.)

Purpose: To translate and cross-culturally adapt the Functional Status Score for the Intensive Care Unit instrument to Turkish and investigate its psychometric properties. Methods: An expert committee supervised forward and backward translation. Thirteen participants reviewed the pre-final version of Turkish Functional Status Score for the Intensive Care Unit instrument providing minor revisions to improve its readability. Two physiotherapists assessed patients ( N  = 50) from a coronary intensive care unit using the Turkish Functional Status Score for the Intensive Care Unit instrument. Results: Internal consistency was excellent (Cronbach's α  = 0.949). Inter-rater reliability and intra-rater reliability were excellent for each of five functional tasks and total scores (intra-class correlation coefficient = 0.955-0.996). The Turkish Functional Status Score for the Intensive Care Unit score had moderate to high correlations with other functional measures as follows: Perme Intensive Care Unit Mobility Score (Spearman's r  = 0.92), Katz Activities of Daily Living ( r  = 0.80), handgrip strength ( r  =  0.76-0.77), and knee extension strength ( r  = 0.70-0.71). Conclusion: The Functional Status Score for the Intensive Care Unit instrument was translated and culturally adapted to Turkish and demonstrated strong psychometric properties, including internal consistency, intra-rater and inter-rater reliability, construct validity, and floor and ceiling effects.Implications for rehabilitationRehabilitation professionals strive to assess and document patient status using validated and reliable outcome measures as part of good clinical practice.Longitudinal evaluation of physical function in the intensive care units is important.The Functional Status Score for the Intensive Care Unit is a validated and reliable physical functioning measurement instrument suitable for the intensive care units.The Functional Status Score for the Intensive Care Unit was translated and culturally adapted to Turkish, and demonstrated strong psychometric properties, including internal consistency, intra-rater reliability, inter-rater reliability, construct validity, and floor and ceiling effects.

Objective: Examine the inter-rater reliability of the activity measure for post-acute care (AM-PAC) inpatient mobility short form (IMSF) when completed by physical therapists (PTs), during routine clinical practice, in a variety of patients with critical illness., Methods: A prospective observational evaluation at single, large academic hospital in the United States. Patients (n = 76) in surgical, medical and neurological intensive care units (ICUs) were evaluated as part of routine clinical practice using the AM-PAC IMSF administered by eight PTs with at least 6 months of experience using this tool. One of two reference rater PTs observed the physical therapy session, and simultaneously scored the AM-PAC IMSF. The reference rater and clinical PTs were blinded to each other's scores with a minimum of 10 assessments completed by each clinical PT. Bland-Altman plots were constructed and intra-class correlation coefficients (ICC) were computed using a random intercept (physical therapy session) model., Results: Eighty one assessments (five patients assessed twice) were scored by both a clinical PT and reference rater PT (total assessments = 162). Bland-Altman plots revealed a mean difference in AM-PAC IMSF scoring of 0.0 (95% limits of agreement: -3.0 to +3.0), with an ICC (95% confidence interval) of 0.957 (0.947-0.964). The ICC (95% confidence interval) for patients in surgical, medical and neurological ICUs was very similar: 0.949 (0.927-0.959), 0.963 (0.946-0.971) and 0.936 (0.886-0.955), respectively., Conclusions: The AM-PAC IMSF demonstrates excellent reliability compared with reference rater PTs when performed by PTs during clinical care across surgical, medical and neurological ICUs., (© 2020 John Wiley & Sons, Ltd.)

Purpose of Review: Given the growing body of critical care clinical research publications, core outcome sets (COSs) are important to help mitigate heterogeneity in outcomes assessed and measurement instruments used, and have potential to reduce research waste. This article provides an update on COS projects in critical care medicine, and related resources and tools for COS developers., Recent Findings: We identified 28 unique COS projects, of which 15 have published results as of May 2020. COS topics relevant to critical care medicine include mechanical ventilation, cardiology, stroke, rehabilitation, and long-term outcomes (LTOs) after critical illness. There are four COS projects for coronavirus disease 2019 (COVID-19), with a 'meta-COS' summarizing common outcomes across these projects. To help facilitate COS development, there are existing resources, standards, guidelines, and tools available from the Core Outcome Measures in Effectiveness Trials Initiative (www.comet-initiative.org/) and the National Institutes of Health-funded Improve LTO project (www.improvelto.com/)., Summary: Many COS projects have been completed in critical care, with more on-going COS projects, including foci from across the spectrum of acute critical care, COVID-19, critical care rehabilitation, and patient recovery and LTOs. Extensive resources are accessible to help facilitate rigorous COS development.

Much is known about how broad eukaryotic phytoplankton groups vary according to nutrient availability in marine ecosystems. However, genus- and species-level dynamics are generally unknown, although important given that adaptation and acclimation processes differentiate at these levels. We examined phytoplankton communities across seasonal cycles in the North Atlantic (BATS) and under different trophic conditions in the eastern North Pacific (ENP), using phylogenetic classification of plastid-encoded 16S rRNA amplicon sequence variants (ASVs) and other methodologies, including flow cytometric cell sorting. Prasinophytes dominated eukaryotic phytoplankton amplicons during the nutrient-rich deep-mixing winter period at BATS. During stratification ('summer') uncultured dictyochophytes formed ∼35 ± 10% of all surface plastid amplicons and dominated those from stramenopile algae, whereas diatoms showed only minor, ephemeral contributions over the entire year. Uncultured dictyochophytes also comprised a major fraction of plastid amplicons in the oligotrophic ENP. Phylogenetic reconstructions of near-full length 16S rRNA sequences established 11 uncultured Dictyochophyte Environmental Clades (DEC). DEC-I and DEC-VI dominated surface dictyochophytes under stratification at BATS and in the ENP, and DEC-IV was also important in the latter. Additionally, although less common at BATS, Florenciella -related clades (FC) were prominent at depth in the ENP. In both ecosystems, pelagophytes contributed notably at depth, with PEC-VIII (Pelagophyte Environmental Clade) and (cultured) Pelagomonas calceolata being most important. Q-PCR confirmed the near absence of P. calceolata at the surface of the same oligotrophic sites where it reached ∼1,500 18S rRNA gene copies ml -1 at the DCM. To further characterize phytoplankton present in our samples, we performed staining and at-sea single-cell sorting experiments. Sequencing results from these indicated several uncultured dictyochophyte clades are comprised of predatory mixotrophs. From an evolutionary perspective, these cells showed both conserved and unique features in the chloroplast genome. In ENP metatranscriptomes we observed high expression of multiple chloroplast genes as well as expression of a selfish element (group II intron) in the psaA gene. Comparative analyses across the Pacific and Atlantic sites support the conclusion that predatory dictyochophytes thrive under low nutrient conditions. The observations that several uncultured dictyochophyte lineages are seemingly capable of photosynthesis and predation, raises questions about potential shifts in phytoplankton trophic roles associated with seasonality and long-term ocean change., (Copyright © 2020 Choi, Jimenez, Needham, Poirier, Bachy, Alexander, Wilken, Chavez, Sudek, Giovannoni and Worden.)

Background: Fatigue is commonly reported by ARDS survivors, but empirical data are scarce., Research Question: This study evaluated fatigue prevalence and associated variables in a prospective study of ARDS survivors., Study Design and Methods: This analysis is part of the ARDSNet Long-Term Outcomes Study (ALTOS) conducted at 38 US hospitals. Using age- and sex-adjusted, time-averaged random effects regression models, we evaluated associations between the validated Functional Assessment of Chronic Illness Therapy-Fatigue Scale with patient and critical illness variables, and with physical, cognitive, and mental health status at 6 and 12 months following ARDS., Results: Among ARDS survivors, 501 of 711 (70%) and 436 of 659 (66%) reported clinically significant symptoms of fatigue at 6 and 12 months, respectively, with 41% and 28% reporting clinically important improvement and worsening (n = 638). At 6 months, the prevalence of fatigue (70%) was greater than that of impaired physical functioning (50%), anxiety (42%), and depression (36%); 46% reported both impaired physical function and fatigue, and 27% reported co-existing anxiety, depression, and fatigue. Fatigue was less severe in men and in those employed prior to ARDS. Critical illness variables (eg, illness severity, length of stay) had little association with fatigue symptoms. Worse physical, cognitive, and mental health symptoms were associated with greater fatigue at both the 6- and 12-month follow-up., Interpretation: During the first year following ARDS, more than two-thirds of survivors reported clinically significant fatigue symptoms. Due to frequent co-occurrence, clinicians should evaluate and manage survivors' physical, cognitive, and mental health status when fatigue is endorsed., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: With an increasing number of follow-up studies of acute respiratory failure survivors, there is need for a better understanding of participant retention and its reporting in this field of research. Hence, our objective was to synthesize participant retention data and associated reporting for this field., Methods: Two screeners independently searched for acute respiratory failure survivorship studies within a published scoping review to evaluate subject outcomes after hospital discharge in critical illness survivors., Results: There were 21 acute respiratory failure studies ( n = 4,342 survivors) over 47 follow-up time points. Six-month follow-up (range: 2-60 months) was the most frequently reported time point, in 81% of studies. Only 1 study (5%) reported accounting for loss to follow-up in sample-size calculation. Retention rates could not be calculated for 5 (24%) studies. In 16 studies reporting on retention across all time points, retention ranged from 32% to 100%. Pooled retention rates at 3, 6, 12, and 24 months were 85%, 89%, 82%, and 88%, respectively. Retention rates did not significantly differ by publication year, participant mean age, or when comparing earlier (3 months) versus each later follow-up time point (6, 12, or 24 months)., Conclusions: Participant retention was generally high but varied greatly across individual studies and time points, with 24% of studies reporting inadequate data to calculate retention rate. High participant retention is possible, but resources for optimizing retention may help studies retain participants. Improved reporting guidelines with greater adherence would be beneficial., (Copyright © 2020 by Daedalus Enterprises.)

Preventing, treating, and promoting recovery from critical illness due to pulmonary disease are foundational goals of the critical care community and the NHLBI. Decades of clinical research in acute respiratory distress syndrome, acute respiratory failure, pneumonia, and sepsis have yielded improvements in supportive care, which have translated into improved patient outcomes. Novel therapeutics have largely failed to translate from promising preclinical findings into improved patient outcomes in late-phase clinical trials. Recent advances in personalized medicine, "big data," causal inference using observational data, novel clinical trial designs, preclinical disease modeling, and understanding of recovery from acute illness promise to transform the methods of pulmonary and critical care clinical research. To assess the current state of, research priorities for, and future directions in adult pulmonary and critical care research, the NHLBI assembled a multidisciplinary working group of investigators. This working group identified recommendations for future research, including 1 ) focusing on understanding the clinical, physiological, and biological underpinnings of heterogeneity in syndromes, diseases, and treatment response with the goal of developing targeted, personalized interventions; 2 ) optimizing preclinical models by incorporating comorbidities, cointerventions, and organ support; 3 ) developing and applying novel clinical trial designs; and 4 ) advancing mechanistic understanding of injury and recovery to develop and test interventions targeted at achieving long-term improvements in the lives of patients and families. Specific areas of research are highlighted as especially promising for making advances in pneumonia, acute hypoxemic respiratory failure, and acute respiratory distress syndrome.

Background: Participant retention is a major challenge in clinical research, especially in studies with multiple, longitudinal research assessments. Despite the importance of retention methods, there is little empirical research on how cohort retention efforts are perceived by study participants., Research Question: To evaluate the association between the number of attempts undertaken to contact participants for research assessments in a longitudinal cohort study and participants' feeling of being bothered regarding such contact attempts., Study Design and Methods: Secondary analysis of 315 ARDS survivors participating in a prospective study using comprehensive strategies for participant follow-up at 6 and 12 months that achieved > 95% participant retention. After completing a 242-question research assessment lasting 20 to 40 min, participants were surveyed for feedback., Results: At 6 and 12 months, only 5% and 8% of participants, respectively, reported being bothered "more than a little bit" by the study contact attempts, with an OR of 1.06 (95% CI, 1.02-1.10) for each contact attempt. Participants' mental health symptoms at follow-up assessment were not associated with reports of being bothered., Interpretation: Comprehensive cohort retention efforts can achieve > 95% retention rates in a national longitudinal study, with most participants reporting little or no bother by contact attempts. Despite a high frequency of mental health symptoms in this population, such symptoms were not associated with participant feedback regarding contact attempts. Careful training of research staff may be important in achieving such results., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

More than 4 million adults survive a stay in the intensive care unit each year, with many experiencing new or worsening physical disability, mental health problems, and/or cognitive impairments, known as post-intensive care syndrome (PICS). Given the prevalence and magnitude of physical impairments after critical illness, many survivors, including those recovering from COVID-19, could benefit from physical therapist services after hospital discharge. However, due to the relatively recent recognition and characterization of PICS, there may be limited awareness and understanding of PICS among physical therapists practicing in home health care and community-based settings. This lack of awareness may lead to inappropriate and/or inadequate rehabilitation service provision. While this perspective article provides information relevant to all physical therapists, it is aimed toward those providing rehabilitation services outside of the acute and postacute inpatient settings. This article reports the prevalence and clinical presentation of PICS and provides recommendations for physical examination and outcomes measures, plan of care, and intervention strategies. The importance of providing patient and family education, coordinating community resources including referring to other health care team members, and community-based rehabilitation service options is emphasized. Finally, this perspective article discusses current challenges for optimizing outcomes for people with PICS and suggests future directions for research and practice., (© 2020 American Physical Therapy Association.)

Objective: To expand an existing validated measure of basic mobility (Activity Measure for Post-Acute Care [AM-PAC]) for patients at the lowest levels of function., Design: Item replenishment for existing item response theory (IRT) derived measure via (1) idea generation and creation of potential new items, (2) item calibration and field testing, and (3) longitudinal pilot test., Setting: Two tertiary acute care hospitals., Participants: Consecutive inpatients (N=502) ≥18 years old, with an AM-PAC Inpatient Mobility Short Form (IMSF) raw score ≤15. For the longitudinal pilot test, 8 inpatients were evaluated., Results: Fifteen new AM-PAC items were developed, 2 of which improved mobility measurement at the lower levels of functioning. Specifically, with the 2 new items, the floor effect of the AM-PAC IMSF was reduced by 19%, statistical power and measurement breadth were greater, and there was greater measurement sensitivity in longitudinal pilot testing., Conclusion: Adding 2 new items to the AM-PAC IMSF lowered the floor and increased statistical power, measurement breadth, and sensitivity., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: In the intensive care unit (ICU), inactivity is common, contributing to ICU-acquired weakness and poor outcomes. Actigraphy may be useful for measuring activity in the ICU., Objectives: To use actigraphy to characterize inactivity and activity in critically ill patients., Methods: This prospective observational study involved 48-h wrist actigraphy in medical ICU (MICU) patients, with activity data captured across 30-s epochs. Inactivity (zero-activity epochs) and activity (levels of non-zero activity) were summarized across key patient (e.g., age) and clinical (e.g., mechanical ventilation status) variables, and compared using multivariable regression., Results: Overall, 189,595 30-s epochs were collected in 34 MICU patients. Zero-activity (inactivity) comprised 122,865 (65%) of epochs; these epochs were 24% and 13% more prevalent, respectively, in patients receiving mechanical ventilation (versus none, p < 0.001) and in the highest (versus lowest) organ failure score tertile (p = 0.03). Ambulatory (versus non-ambulatory) patients exhibited more non-zero activity (35 more movements per epoch, p < 0.001), while those in the highest (versus lowest) organ failure score tertile exhibited less activity (22 fewer movements per epoch, p = 0.03). Significant inactivity/activity differences were not observed when evaluated based on age, sedation, or restraint status., Conclusions: Actigraphy demonstrated that MICU patients are profoundly inactive, including those who are young, non-sedated and non-restrained. Hence, ICU-specific, non-patient-related factors may contribute to inactivity, an issue requiring further investigation., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Published by Elsevier Inc.)

Background: There is scant literature on the barriers to rehabilitation for patients discharged from the intensive care unit (ICU) to acute care wards., Objectives: The objective of this study was to assess ward-based rehabilitation practices and barriers and assess knowledge and perceptions of ward clinicians regarding health concerns of ICU survivors., Methods, Design, Setting, and Participants: This was a single-centre survey of multidisciplinary healthcare professionals caring for ICU survivors in an Australian tertiary teaching hospital., Main Outcome Measures: The main outcome measures were knowledge of post-intensive care syndrome (PICS) amongst ward clinicians, perceptions of ongoing health concerns with current rehabilitation practices, and barriers to inpatient rehabilitation for ICU survivors., Results: The overall survey response rate was 35% (198/573 potential staff). Most respondents (66%, 126/190) were unfamiliar with the term PICS. A majority of the respondents perceived new-onset physical weakness, sleep disturbances, and delirium as common health concerns amongst ICU survivors on acute care wards. There were multifaceted barriers to patient mobilisation, with inadequate multidisciplinary staffing, lack of medical order for mobilisation, and inadequate physical space near the bed as common institutional barriers and patient frailty and cardiovascular instability as the commonly perceived patient-related barriers. A majority of the surveyed ward clinicians (66%, 115/173) would value education on health concerns of ICU survivors to provide better patient care., Conclusion: There are multiple potentially modifiable barriers to the ongoing rehabilitation of ICU survivors in an acute care hospital. Addressing these barriers may have benefits for the ongoing care of ICU survivors., (Copyright © 2019 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Delirium is an acute disorder of attention and cognition. It occurs across the life span, yet it is particularly common among older adults, and is closely linked with underlying neurocognitive disorders. Evidence is mounting that intervening on delirium may represent an important opportunity for delaying the onset or progression of dementia. To accelerate the current understanding of delirium, the Network for Investigation of Delirium: Unifying Scientists (NIDUS) held a conference "Advancing Delirium Research: A Scientific Think Tank" in June 2019. This White Paper encompasses the major knowledge and research gaps identified at the conference: advancing delirium definition and measurement, understanding delirium pathophysiology, and prevention and treatment of delirium. A roadmap of research priorities is proposed to advance the field in a systematic, interdisciplinary, and coordinated fashion. A call is made for an international consortium and biobank targeted to delirium, as well as a public health campaign to advance the field., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Objectives: With decreasing mortality in PICUs, a growing number of survivors experience long-lasting physical impairments. Early physical rehabilitation and mobilization during critical illness are safe and feasible, but little is known about the prevalence in PICUs. We aimed to evaluate the prevalence of rehabilitation for critically ill children and associated barriers., Design: National 2-day point prevalence study., Setting: Eighty-two PICUs in 65 hospitals across the United States., Patients: All patients admitted to a participating PICU for greater than or equal to 72 hours on each point prevalence day., Interventions: None., Measurements and Main Results: The primary outcome was prevalence of physical therapy- or occupational therapy-provided mobility on the study days. PICUs also prospectively collected timing of initial rehabilitation team consultation, clinical and patient mobility data, potential mobility-associated safety events, and barriers to mobility. The point prevalence of physical therapy- or occupational therapy-provided mobility during 1,769 patient-days was 35% and associated with older age (adjusted odds ratio for 13-17 vs < 3 yr, 2.1; 95% CI, 1.5-3.1) and male gender (adjusted odds ratio for females, 0.76; 95% CI, 0.61-0.95). Patients with higher baseline function (Pediatric Cerebral Performance Category, ≤ 2 vs > 2) less often had rehabilitation consultation within the first 72 hours (27% vs 38%; p < 0.001). Patients were completely immobile on 19% of patient-days. A potential safety event occurred in only 4% of 4,700 mobility sessions, most commonly a transient change in vital signs. Out-of-bed mobility was negatively associated with the presence of an endotracheal tube (adjusted odds ratio, 0.13; 95% CI, 0.1-0.2) and urinary catheter (adjusted odds ratio, 0.28; 95% CI, 0.1-0.6). Positive associations included family presence in children less than 3 years old (adjusted odds ratio, 4.55; 95% CI, 3.1-6.6)., Conclusions: Younger children, females, and patients with higher baseline function less commonly receive rehabilitation in U.S. PICUs, and early rehabilitation consultation is infrequent. These findings highlight the need for systematic design of rehabilitation interventions for all critically ill children at risk of functional impairments.

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

Purpose: Poor neuropsychiatric outcomes are common in survivors of critical illness but it is unclear what patient groups to target for interventions to improve mental health. We compared anxiety, depression, and post-traumatic stress disorder (PTSD) symptoms and health-related quality of life (HrQoL) across different subgroups of Intensive Care Unit (ICU) survivors., Materials and Methods: A single-center cohort study was conducted in a mixed-ICU in the Netherlands among survivors of an ICU admission ≥48 h (n = 1730). Survivors received a survey one year after discharge, containing the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES/IES-R), and EQ-5D (response rate of 67%). Neuropsychiatric symptoms and quality of life were evaluated in a priori defined subgroups, by chi-square tests and Mann-Whitney U tests., Results: Symptoms of anxiety (HADS anxiety ≥8), depression (HADS depression ≥8), and PTSD (IES ≥35; IES-R ≥ 1.6) were reported by 34%, 33%, and 19% of ICU survivors, with a median HrQoL utility score of 0.81 (IQR:0.65-1.00). These figures were similar for survivors of ARDS, sepsis, severe multiple organ failure (SOFA>11), or ICU stay ≥7 days., Conclusions: This underlines the importance of prevention and treatment for neuropsychiatric symptoms in ICU survivors in general, not only in specific patient groups., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: Growing evidence suggests that early mobilization benefits intensive care unit (ICU) patients. However, national practices and the culture of individual ICUs influence mobilization activities., Materials and Methods: In a 1-day, Swiss point prevalence study conducted in 35 ICUs (representing 45% of all ICUs), the highest level of mobilization for mechanically ventilated patients was characterized using the validated ICU Mobility Scale, along with data collection for potential safety events and mobilization barriers., Results: Among 161 mechanically ventilated patients, a total of 33% (n = 53) had active mobilization, with walking achieved by only 2% (n = 4). More severe organ failure was associated with lower mobilization (respiratory Sequential Organ Failure Assessment score: P = .037, cardiac: P = .008, neurology: P < .001). Barriers to mobilization were reported in 71% (n = 115), with deep sedation significantly higher among patients receiving passive versus active mobilization (14% vs 0%, P = .005). Potential safety events occurred in 20% (n = 33) of patients without significant differences between passive and active mobilization. Availability of physiotherapists and appropriate equipment were not reported barriers., Conclusion: Mobilization during mechanical ventilation occurred infrequently with greater organ failure associated with lower mobilization. Addressing the identified modifiable barriers via structured efforts to achieve multidisciplinary culture change is essential to decrease the common use of bed rest in Swiss ICUs.

Ecosystems are controlled by 'bottom-up' (resources) and 'top-down' (predation) forces. Viral infection is now recognized as a ubiquitous top-down control of microbial growth across ecosystems but, at the same time, cell death by viral predation influences, and is influenced by, resource availability. In this Review, we discuss recent advances in understanding the biogeochemical impact of viruses, focusing on how metabolic reprogramming of host cells during lytic viral infection alters the flow of energy and nutrients in aquatic ecosystems. Our synthesis revealed several emerging themes. First, viral infection transforms host metabolism, in part through virus-encoded metabolic genes; the functions performed by these genes appear to alleviate energetic and biosynthetic bottlenecks to viral production. Second, viral infection depends on the physiological state of the host cell and on environmental conditions, which are challenging to replicate in the laboratory. Last, metabolic reprogramming of infected cells and viral lysis alter nutrient cycling and carbon export in the oceans, although the net impacts remain uncertain. This Review highlights the need for understanding viral infection dynamics in realistic physiological and environmental contexts to better predict their biogeochemical consequences.

Background: Survivors of critical illness often experience poor outcomes after hospitalisation, including delayed return to work, which carries substantial economic consequences., Objective: To conduct a systematic review and meta-analysis of return to work after critical illness., Methods: We searched PubMed, Embase, PsycINFO, CINAHL and Cochrane Library from 1970 to February 2018. Data were extracted, in duplicate, and random-effects meta-regression used to obtain pooled estimates., Results: Fifty-two studies evaluated return to work in 10 015 previously employed survivors of critical illness, over a median (IQR) follow-up of 12 (6.25-38.5) months. By 1-3, 12 and 42-60 months' follow-up, pooled return to work prevalence (95% CI) was 36% (23% to 49%), 60% (50% to 69%) and 68% (51% to 85%), respectively ( τ 2 =0.55, I 2 =87%, p=0.03). No significant difference was observed based on diagnosis (acute respiratory distress syndrome (ARDS) vs non-ARDS) or region (Europe vs North America vs Australia/New Zealand), but was observed when comparing mode of employment evaluation (in-person vs telephone vs mail). Following return to work, 20%-36% of survivors experienced job loss, 17%-66% occupation change and 5%-84% worsening employment status (eg, fewer work hours). Potential risk factors for delayed return to work include pre-existing comorbidities and post-hospital impairments (eg, mental health)., Conclusion: Approximately two-thirds, two-fifths and one-third of previously employed intensive care unit survivors are jobless up to 3, 12 and 60 months following hospital discharge. Survivors returning to work often experience job loss, occupation change or worse employment status. Interventions should be designed and evaluated to reduce the burden of this common and important problem for survivors of critical illness., Trial Registration Number: PROSPERO CRD42018093135., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Giant viruses have remarkable genomic repertoires-blurring the line with cellular life-and act as top-down controls of eukaryotic plankton. However, to date only six cultured giant virus genomes are available from the pelagic ocean. We used at-sea flow cytometry with staining and sorting designed to target wild predatory eukaryotes, followed by DNA sequencing and assembly, to recover novel giant viruses from the Pacific Ocean. We retrieved four 'PacV' partial genomes that range from 421 to 1605 Kb, with 13 contigs on average, including the largest marine viral genomic assembly reported to date. Phylogenetic analyses indicate that three of the new viruses span a clade with deep-branching members of giant Mimiviridae , incorporating the Cafeteria roenbergensis virus, the uncultivated terrestrial Faunusvirus, one PacV from a choanoflagellate and two PacV with unclear hosts. The fourth virus, oPacV-421, is phylogenetically related to viruses that infect haptophyte algae. About half the predicted proteins in each PacV have no matches in NCBI nr ( e -value < 10 -5 ), totalling 1735 previously unknown proteins; the closest affiliations of the other proteins were evenly distributed across eukaryotes, prokaryotes and viruses of eukaryotes. The PacVs encode many translational proteins and two encode eukaryotic-like proteins from the Rh family of the ammonium transporter superfamily, likely influencing the uptake of nitrogen during infection. cPacV-1605 encodes a microbial viral rhodopsin (VirR) and the biosynthesis pathway for the required chromophore, the second finding of a choanoflagellate-associated virus that encodes these genes. In co-collected metatranscriptomes, 85% of cPacV-1605 genes were expressed, with capsids, heat shock proteins and proteases among the most highly expressed. Based on orthologue presence-absence patterns across the PacVs and other eukaryotic viruses, we posit the observed viral groupings are connected to host lifestyles as heterotrophs or phototrophs. This article is part of a discussion meeting issue 'Single cell ecology'.

Muscle mitochondrial dysfunction is implicated in intensive care unit-acquired weakness, but there is no serum biomarker of muscle mitochondrial function for critical illness survivors. Higher serum growth differentiation factor-15 (GDF-15) is a biomarker of inherited mitochondrial myopathy disease and is associated with mortality in several age-related diseases. Among 142 older (age ≥ 65 years) survivors of acute respiratory failure, we found that higher serum GDF-15 measured during the week prior to hospital discharge was cross-sectionally associated with weaker diaphragm, limb and hand-grip strength, and longitudinally associated with lower rates of functional recovery over 6 months, independent of age, sex, pre-existing disability, comorbidity, frailty, Acute Physiology and Chronic Health Evaluation II scores and concurrent interleukin-6 levels., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

An estimated 14.1 million patients survive sepsis each year. Many survivors experience poor long-term outcomes, including new or worsened neuropsychological impairment; physical disability; and vulnerability to further health deterioration, including recurrent infection, cardiovascular events, and acute renal failure. However, clinical trials and guidelines have focused on shorter-term survival, so there are few data on promoting longer-term recovery. To address this unmet need, the International Sepsis Forum convened a colloquium in February 2018 titled "Understanding and Enhancing Sepsis Survivorship." The goals were to identify gaps and limitations of current research and shorter- and longer-term priorities for understanding and enhancing sepsis survivorship. Twenty-six experts from eight countries participated. The top short-term priorities identified by nominal group technique culminating in formal voting were to better leverage existing databases for research, develop and disseminate educational resources on postsepsis morbidity, and partner with sepsis survivors to define and achieve research priorities. The top longer-term priorities were to study mechanisms of long-term morbidity through large cohort studies with deep phenotyping, build a harmonized global sepsis registry to facilitate enrollment in cohorts and trials, and complete detailed longitudinal follow-up to characterize the diversity of recovery experiences. This perspective reviews colloquium discussions, the identified priorities, and current initiatives to address them.

Giant viruses are remarkable for their large genomes, often rivaling those of small bacteria, and for having genes thought exclusive to cellular life. Most isolated to date infect nonmarine protists, leaving their strategies and prevalence in marine environments largely unknown. Using eukaryotic single-cell metagenomics in the Pacific, we discovered a Mimiviridae lineage of giant viruses, which infects choanoflagellates, widespread protistan predators related to metazoans. The ChoanoVirus genomes are the largest yet from pelagic ecosystems, with 442 of 862 predicted proteins lacking known homologs. They are enriched in enzymes for modifying organic compounds, including degradation of chitin, an abundant polysaccharide in oceans, and they encode 3 divergent type-1 rhodopsins (VirR) with distinct evolutionary histories from those that capture sunlight in cellular organisms. One (VirR DTS ) is similar to the only other putative rhodopsin from a virus (PgV) with a known host (a marine alga). Unlike the algal virus, ChoanoViruses encode the entire pigment biosynthesis pathway and cleavage enzyme for producing the required chromophore, retinal. We demonstrate that the rhodopsin shared by ChoanoViruses and PgV binds retinal and pumps protons. Moreover, our 1.65-Å resolved VirR DTS crystal structure and mutational analyses exposed differences from previously characterized type-1 rhodopsins, all of which come from cellular organisms. Multiple VirR types are present in metagenomes from across surface oceans, where they are correlated with and nearly as abundant as a canonical marker gene from Mimiviridae Our findings indicate that light-dependent energy transfer systems are likely common components of giant viruses of photosynthetic and phagotrophic unicellular marine eukaryotes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Background: Delirium is common in hospitalized patients and is associated with worse outcomes. Antipsychotics are commonly used; however, the associated benefits and harms are unclear., Purpose: To conduct a systematic review evaluating the benefits and harms of antipsychotics to treat delirium in adults., Data Sources: PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception to July 2019 without language restrictions., Study Selection: Randomized controlled trials (RCTs) of antipsychotic versus placebo or another antipsychotic, and prospective observational studies reporting harms., Data Extraction: One reviewer extracted data and assessed strength of evidence (SOE) for critical outcomes, with confirmation by another reviewer. Risk of bias was assessed independently by 2 reviewers., Data Synthesis: Across 16 RCTs and 10 observational studies of hospitalized adults, there was no difference in sedation status (low and moderate SOE), delirium duration, hospital length of stay (moderate SOE), or mortality between haloperidol and second-generation antipsychotics versus placebo. There was no difference in delirium severity (moderate SOE) and cognitive functioning (low SOE) for haloperidol versus second-generation antipsychotics, with insufficient or no evidence for antipsychotics versus placebo. For direct comparisons of different second-generation antipsychotics, there was no difference in mortality and insufficient or no evidence for multiple other outcomes. There was little evidence demonstrating neurologic harms associated with short-term use of antipsychotics for treating delirium in adult inpatients, but potentially harmful cardiac effects tended to occur more frequently., Limitations: Heterogeneity was present in terms of dose and administration route of antipsychotics, outcomes, and measurement instruments. There was insufficient or no evidence regarding multiple clinically important outcomes., Conclusion: Current evidence does not support routine use of haloperidol or second-generation antipsychotics to treat delirium in adult inpatients., Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).

Background: Delirium is an acute disorder marked by impairments in attention and cognition, caused by an underlying medical problem. Antipsychotics are used to prevent delirium, but their benefits and harms are unclear., Purpose: To conduct a systematic review evaluating the benefits and harms of antipsychotics for prevention of delirium in adults., Data Sources: PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception through July 2019, without restrictions based on study setting, language of publication, or length of follow-up., Study Selection: Randomized, controlled trials (RCTs) that compared an antipsychotic with placebo or another antipsychotic, and prospective observational studies with a comparison group., Data Extraction: One reviewer extracted data and graded the strength of the evidence, and a second reviewer confirmed the data. Two reviewers independently assessed the risk of bias., Data Synthesis: A total of 14 RCTs were included. There were no differences in delirium incidence or duration, hospital length of stay (high strength of evidence [SOE]), and mortality between haloperidol and placebo used for delirium prevention. Little to no evidence was found to determine the effect of haloperidol on cognitive function, delirium severity (insufficient SOE), inappropriate continuation, and sedation (insufficient SOE). There is limited evidence that second-generation antipsychotics may lower delirium incidence in the postoperative setting. There is little evidence that short-term use of antipsychotics was associated with neurologic harms. In some of the trials, potentially harmful cardiac effects occurred more frequently with antipsychotic use., Limitations: There was significant heterogeneity in antipsychotic dosing, route of antipsychotic administration, assessment of outcomes, and adverse events. There were insufficient or no data available to draw conclusions for many of the outcomes., Conclusion: Current evidence does not support routine use of haloperidol or second-generation antipsychotics for prevention of delirium. There is limited evidence that second-generation antipsychotics may lower the incidence of delirium in postoperative patients, but more research is needed. Future trials should use standardized outcome measures., Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).

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.

Purpose/objective: Intensive care unit (ICU) survivors frequently experience long-lasting mental health, cognitive, and physiologic challenges. Psychologists have a role in providing interventions to reduce patient distress during critical illness and improve outcomes. There is limited data regarding psychology consultations in the ICU. This brief report characterizes psychology consultations in a medical intensive care unit (MICU) in an academic medical center., Method: Psychology consultations were prospectively tracked, with patient-related data retrospectively collected and analyzed., Results: A total of 79 consecutive psychology consultations occurred at mean of 8 ± 6 days after MICU admission. Reasons for consultation were patient emotional distress (56%), rehabilitation therapy engagement (24%), family engagement (13%), cognitive disturbance (4%), and pain (4%). Patient characteristics were: mean age 56 ± 15 years, 54% women, 53% White, and 34% with psychiatric comorbidity at MICU admission. Patients referred for consultation had a longer MICU length of stay than the total MICU population (12 ± 9 days vs. 4 ± 6 days, p < .01). For consultations for emotional distress compared with limited rehabilitation therapy engagement, patient demographic characteristics were similar, with the exception of women (vs. men) being more commonly consulted for emotional distress (64 vs. 26%, p = .01)., Conclusions: Patients with a longer MICU stay more commonly had a rehabilitation psychology consultation request, typically to provide support for emotional distress or engagement in rehabilitation therapy. Future research should evaluate the effectiveness of psychology interventions in the ICU. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Critical illness can be lethal and devastating to survivors. Improvements in acute care have increased the number of intensive care unit (ICU) survivors. These survivors confront a range of new or worsened health states that collectively are commonly denominated post-intensive care syndrome (PICS). These problems include physical, cognitive, psychological, and existential aspects, among others. Burgeoning interest in improving long-term outcomes for ICU survivors has driven an array of potential interventions to improve outcomes associated with PICS. To date, the most promising interventions appear to relate to very early physical rehabilitation. Late interventions within aftercare and recovery clinics have yielded mixed results, although experience in heart failure programs suggests the possibility that very early case management interventions may help improve intermediate-term outcomes, including mortality and hospital readmission. Predictive models have tended to underperform, complicating study design and clinical referral. The complexity of the health states associated with PICS suggests that careful and rigorous evaluation of multidisciplinary, multimodality interventions-tied to the specific conditions of interest-will be required to address these important problems.

Introduction: Survivors of critical illness often experience significant morbidities, including muscle weakness and impairments in physical functioning. This muscle weakness is associated with longer duration mechanical ventilation, greater hospital costs and increased postdischarge impairments in physical function, quality of life and survival. Compared with standard of care, the benefits of greater protein intake combined with structured exercise started early after the onset of critical illness remain uncertain. However, the combination of protein supplementation and exercise in other populations has demonstrated positive effects on strength and function. In the present study, we will evaluate the effects of a combination of early implementation of intravenous amino acid supplementation and in-bed cycle ergometry exercise versus a 'usual care' control group in patients with acute respiratory failure requiring mechanical ventilation in an intensive care unit (ICU)., Methods and Analysis: In this multicentre, assessor-blinded, randomised controlled trial, we will randomise 142 patients in a 1:1 ratio to usual care (which commonly consists of minimal exercise and under-achievement of guideline-recommended caloric and protein intake goals) versus a combined intravenous amino acid supplementation and in-bed cycle ergometery exercise intervention. We hypothesise that this novel combined intervention will (1) improve physical functioning at hospital discharge; (2) reduce muscle wasting with improved amino acid metabolism and protein synthesis in-hospital and (3) improve patient-reported outcomes and healthcare resource utilisation at 6 months after enrolment. Key cointerventions will be standardised. In-hospital outcome assessments will be conducted at baseline, ICU discharge and hospital discharge. An intent-to-treat analysis will be used to analyse all data with additional per-protocol analyses., Ethics and Dissemination: The trial received ethics approval at each institution and enrolment has begun. These results will inform both clinical practice and future research in the area. We plan to disseminate trial results in peer-reviewed journals, at national and international conferences, and via nutritional and rehabilitation-focused electronic education and knowledge translation platforms., Trial Registration Number: NCT03021902; Pre-results., Competing Interests: Competing interests: For purposes of conducting this NIH/NHLBI-funded clinical trial, Dr Heyland reports a grant and donated amino acid product from Baxter Healthcare Corporation and an equipment loan from Reck Medical Devices. For purposes of conducting this NIH/NHLBI-funded clinical trial, Dr Needham reports a grant and donated amino acid product from Baxter Healthcare Corporation and an equipment loan from Reck Medical Devices. For purposes of conducting this NIH/NHLBI-funded clinical trial, Dr Stapleton reports a grant and donated amino acid product from Baxter Healthcare Corporation and an equipment loan from Reck Medical Devices. Dr Mourtzakis, John Clarke and Andrew Day have nothing to disclose. Dr Files reports grants from National Institute of Health during the conduct of the study. Dr Files also reports a grant and donated amino acid product from Baxter Healthcare Corporation and an equipment loan from Reck Medical Devices. Dr Hough reports grants from NIH during the conduct of the study. Dr Hough also reports a grant and donated amino acid product from Baxter Healthcare Corporation and an equipment loan from Reck Medical Devices. Nicolaas E Deutz declares no conflicts of interests, but discloses that he is a coinventor of several patents, owned by others, has served on scientific advisory boards for Novartis and Baxter and has been a consultant for Abbott Nutrition, Ajinomoto, OCERA and VitaNext. Texas A&M CTRAL receives funding from NIH, NSF, Abbott Nutrition, ICAAS, ESPEN fellowship, George Abramson Donation, Yani Mizubuti Donation and Internal Grants., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Physician Orders for Life-Sustaining Treatment (POLST) programs have expanded rapidly, but evaluating their impact on hospital care is challenging., Objectives: To demonstrate how careful study design can reveal POLST's impact at hospital admission and why analyses of state registry data are unlikely to capture POLST's effects., Design: Prospective cohort study., Setting and Participants: Adult in-patients with Do Not Intubate and/or Do Not Resuscitate (DNR/I) orders in the electronic medical record at the time of discharge from Johns Hopkins Hospital over 18 months. For patients with unplanned readmissions within 30 days, records were reviewed to determine if a Maryland Medical Order for Life-Sustaining Treatment (MOLST) form was presented and for the time from readmission to a DNR/I order in the EMR. Analyses were stratified by whether patients could communicate or were accompanied by a proxy at readmission., Results: Among 1,507 patients with DNR/I orders at discharge, 124 (8%) had unplanned readmissions, 112 (90%) could communicate or were accompanied by a proxy at readmission, and 12 (10%) could not communicate and were unaccompanied. For patients who were unaccompanied and could not communicate, MOLST significantly decreased the median time from readmission to DNR/I order (1.2 vs 27.1 hours, P = .001), but this association was greatly attenuated among patients who could communicate or were accompanied by a proxy (16.4 vs 25.4 hours P = .10)., Conclusion: Among patients who wanted to avoid intubation and/or CPR, MOLST forms were protective when the patient was unaccompanied by a healthcare proxy at admission and could not communicate. Fewer than 10% of patients met these criteria during unplanned readmissions, and state registry data does not allow this sub-population to be identified., Competing Interests: The authors have declared that no competing interests exist.

Light plays a central role on primary productivity of aquatic systems. Yet, its potential impact on the degradation of photosynthetically produced biomass is not well understood. We investigated the patterns of light-induced particle breakdown and bacterial assimilation of detrital C and N using 13 C and 15 N labeled freeze-thawed diatom cells incubated in laboratory microcosms with a marine microbial community freshly collected from the Pacific Ocean. Particles incubated in the dark resulted in increased bacterial counts and dissolved organic carbon concentrations compared to those incubated in the light. Light also influenced the attached and free-living microbial community structure as detected by 16S rRNA gene amplicon sequencing. For example, Sphingobacteriia were enriched on dark-incubated particles and taxa from the family Flavobacteriaceae and the genus Pseudoalteromonas were numerically enriched on particles in the light. Isotope incorporation analysis by phylogenetic microarray and NanoSIMS (a method called Chip-SIP) identified free-living and attached microbial taxa able to incorporate N and C from the particles. Some taxa, including members of the Flavobacteriaceae and Cryomorphaceae, exhibited increased isotope incorporation in the light, suggesting the use of photoheterotrophic metabolisms. In contrast, some members of Oceanospirillales and Rhodospirillales showed decreased isotope incorporation in the light, suggesting that their heterotrophic metabolism, particularly when occurring on particles, might increase at night or may be inhibited by sunlight. These results show that light influences particle degradation and C and N incorporation by attached bacteria, suggesting that the transfer between particulate and free-living phases are likely affected by external factors that change with the light regime, such as time of day, water column depth and season.

Rationale: Increasingly, patients are surviving acute respiratory failure (ARF), prompting the need to better understand standardized outcome measures commonly used during ARF follow-up studies. Objectives: Investigate standardized outcome measures (patient-reported physical and mental health measures, and cognitive testing) compared with findings from semistructured, qualitative interviews. Methods: As part of two ARF multicenter follow-up studies, standardized outcome measures were obtained, followed by qualitative evaluation via an in-depth, semistructured interview conducted and coded by two independent researchers. Qualitative interviews revealed the following post-ARF survivorship themes: physical impairment; anxiety, depression, and post-traumatic stress disorder symptoms; and cognitive impairment. Scores from standardized measures related to these themes were compared for ARF survivors reporting versus not reporting these themes in their qualitative interviews. Results: Of 59 invited ARF survivors, 48 (81%) completed both standardized outcome measures and qualitative interviews. Participants' median (interquartile range) age was 53 (43-64) years; 54% were female, and 88% were living independently before hospitalization. The two independent reviewers classifying the presence or absence of themes from the qualitative interviews had excellent agreement (κ = 0.80). There were significantly worse scores on standardized outcome measures for survivors reporting (vs. not reporting) physical and mental health impairments in their qualitative interviews. However, standardized cognitive test scores did not differ between patients reporting versus not reporting cognitive impairments in their qualitative interviews. Conclusions: These findings support the use of recommended, commonly used standardized outcome measures for physical and mental health impairments in ARF survivorship research. However, caution is needed in interpreting self-reported cognitive function compared with standardized cognitive testing.

Objectives: The Critical Care Choosing Wisely Task Force recommends that intensivists offer patients at high risk for death or severe functional impairment the option of pursuing care focused on comfort. We tested the a priori hypothesis that intensivists who are prompted to document patient prognosis are more likely to disclose prognosis and offer comfort-focused care., Design: Randomized controlled trial (clinicaltrials.gov: NCT02721810)., Setting: High-fidelity Simulation Center in Baltimore, MD., Participants: One hundred sixteen intensivists from 17 states., Intervention: All intensivists reviewed a paper-based medical record for a hypothetical patient on ICU day 3 and answered four survey questions about the patient's medical management. Intensivists randomized to the intervention group answered three additional questions about patient prognosis. Thereafter, each intensivist participated in a standardized, video-recorded, simulated family meeting with an actor performing a standardized portrayal of the patient's daughter., Measurements and Main Results: Two blinded intensivists reviewed deidentified written transcripts of all simulated family meetings. The primary outcome was the blinded reviewers' assessment that the intensivist had presented the option of care focused entirely on comfort. Secondary outcomes included disclosing risk of death. All outcomes were planned prior to data collection. Among the 63 intensivists randomized to the intervention, 50 (79%) expected the patient to die during the hospitalization and 58 (92%) expected the patient to have new functional impairments preventing independent living. Intensivists in the intervention versus control group were no more likely to offer the option of care focused on comfort (13% vs 13%; 95% CI, -13% to 12%; p = 1.0) but were more likely to inform the daughter that her father was sick enough to die (68% vs 43%; 95% CI, 5-44%; p = 0.01)., Conclusions: Documenting prognosis may help intensivists disclose prognosis to ICU proxies, but in isolation, it is unlikely to change the treatment options offered during initial family meetings.

Viruses provide top-down control on microbial communities, yet their direct study in natural environments was hindered by culture limitations. The advance of bioinformatics enables cultivation-independent study of viruses. Many studies assemble new viral genomes and study viral diversity using marker genes from free viruses. Here we use cellular metatranscriptomics to study active community-wide viral infections. Recruitment to viral contigs allows tracking infection dynamics over time and space. Our assemblies represent viral populations, but appear biased towards low diversity viral taxa. Tracking relatives of published T4-like cyanophages and pelagiphages reveals high genomic continuity. We determine potential hosts by matching dynamics of infection with abundance of particular microbial taxa. Finally, we quantify the relative contribution of cyanobacteria and viruses to photosystem-II psbA (reaction center) expression in our study sites. We show sometimes >50% of all cyanobacterial+viral psbA expression is of viral origin, highlighting the contribution of viruses to photosynthesis and oxygen production.

Rationale: The majority of ICU patients lack decision-making capacity at some point during their ICU stay. However the extent to which proxy decision-makers are engaged in decisions about their patient's care is challenging to quantify., Objectives: To assess 1)whether proxies know their patient's actual code status as recorded in the electronic medical record (EMR), and 2)whether code status orders reflect ICU patient preferences as reported by proxy decision-makers., Methods: We enrolled proxy decision-makers for 96 days starting January 4, 2016. Proxies were asked about the patient's goals of care, preferred code status, and actual code status. Responses were compared to code status orders in the EMR at the time of interview. Characteristics of patients and proxies who correctly vs incorrectly identified actual code status were compared, as were characteristics of proxies who reported a preferred code status that did vs did not match actual code status., Measurements and Main Results: Among 111 proxies, 42 (38%) were incorrect or unsure about the patient's actual code status and those who were correct vs. incorrect or unsure were similar in age, race, and years of education (P>0.20 for all comparisons). Twenty-nine percent reported a preferred code status that did not match the patient's code status in the EMR. Matching preferred and actual code status was not associated with a patient's age, gender, income, admission diagnosis, or subsequent in-hospital mortality or with proxy age, gender, race, education level, or relation to the patient (P>0.20 for all comparisons)., Conclusions: More than 1 in 3 proxies is incorrect or unsure about their patient's actual code status and more than 1 in 4 proxies reported that a preferred code status that did not match orders in the EMR. Proxy age, race, gender and education level were not associated with correctly identifying code status or code status concordance., Competing Interests: The authors have declared that no competing interests exist.