Smart Phone/Ecological Momentary Assessment of Sleep and Daytime Symptoms Among Older Adults With Insomnia.

OBJECTIVES: To employ smart phone/ecological momentary assessment (EMA) methods to evaluate the impact of insomnia on daytime symptoms among older adults. DESIGN: Prospective cohort study SETTING: Academic medical center PARTICIPANTS: Twenty-nine older adults with insomnia (M age = 67.5 ± 6.6 years, 69% women) and 34 healthy sleepers (M age = 70.4 ± 5.6 years, 65% women). MEASUREMENTS: Participants wore an actigraph, completed daily sleep diaries, and completed the Daytime Insomnia Symptoms Scale (DISS) via smart phone 4x/day for 2 weeks (i.e., 56 survey administrations across 14 days). RESULTS: Relative to healthy sleepers, older adults with insomnia demonstrated more severe insomnia symptoms in all DISS domains (alert cognition, positive mood, negative mood, and fatigue/sleepiness). A series of mixed model analyses were performed using the Benjamini-Hochberg procedure for correcting false discovery rate (BH-FDR) and an adjusted p-value <0.05. Among older adults with insomnia, all five prior-night sleep diary variables (sleep onset latency, wake after sleep onset, sleep efficiency, total sleep time, and sleep quality) were significantly associated with next-day insomnia symptoms (i.e., all four DISS domains). The median, first and third quintiles of the effect sizes (R2) of the association analyses were 0.031 (95% confidence interval (CI: [0.011,0.432]), 0.042(CI: [0.014,0.270]), 0.091 (CI:[0.014,0.324]). CONCLUSION: Results support the utility of smart phone/EMA assessment among older adults with insomnia. Clinical trials incorporating smart phone/EMA methods, including EMA as an outcome measure, are warranted.

Mental Health Consequences of Shift Work: An Updated Review.

PURPOSE OF REVIEW: Approximately 25% of employed individuals engage in shift work, which can substantially alter opportunities for restorative sleep. Being tired on the job can lead to safety risks in professions such as healthcare, first responders, manufacturing, and numerous others. In addition to the physical stress and health consequences of shift work, recent evidence links shift work to poor mental health outcomes. The current review examines the literature from 2016 onward, emphasizing the impact of shift work on mental health. RECENT FINDINGS: Shift work is associated with considerable impacts on sleep, depressed mood and anxiety, substance use, impairments in cognition, lower quality of life, and even suicidal ideation. Pronounced sleep disturbances frequently underlie the mental health consequences of shift work. Shift work can have physical, mental health, and safety consequences. Future research should aim to better understand the interplay of shift work, sleep, and mental health and seek to mitigate the adverse consequences of shift work.

A Pilot Study of Ultrasonography-Naïve Operators' Ability to Use Tele-Ultrasonography to Assess the Heart and Lung.

INTRODUCTION: Remotely tele-mentored ultrasound (RTMUS) involves the real-time guidance of US-naïve providers as they perform point-of-care ultrasound (POCUS) by remotely located, US-proficient providers via telemedicine. The concordance between RTMUS and POCUS in the evaluation of critically ill patients has not been reported. This study sought to evaluate the concordance between RTMUS and POCUS for the cardiopulmonary evaluation of patients in acute respiratory insufficiency and/or shock. METHODS: Ultrasound-naÏve nurses performed RTMUS on critically ill patients. Concordance between RTMUS and POCUS (performed by critical care fellows) in the evaluation of the heart and lungs was reported. The test characteristics of RTMUS were calculated using POCUS as a gold standard. Concordance between RTMUS and available transthoracic echocardiography (TTE) and computed tomography (CT) scans was also reported. RESULTS: Twenty patients were enrolled. Concordance between RTMUS and POCUS was good (90%-100%) for left ventricle function, right ventricle (RV) dilatation/dysfunction, pericardial effusion, lung sliding, pulmonary interstitial syndrome, pleural effusion, and fair (80%) for lung consolidation. Concordance between RTMUS and TTE or CT was similar. RTMUS was highly specific (88%-100%) for all abnormalities evaluated and highly sensitive (89%-100%) for most abnormalities although sensitivity for the detection of RV dilatation/dysfunction (33%) and pulmonary interstitial syndrome (71%) was negatively impacted by false negatives. CONCLUSIONS: RTMUS may be a reasonable substitute for POCUS in the cardiopulmonary evaluation of patients with acute respiratory insufficiency and/or shock. These findings should be validated on a larger scale.

Point-of-Care Teleultrasound: A Systematic Review.

Background: Telemedicine and point-of-care ultrasound have merged to create a field known as teleultrasound (TUS). Real-time TUS involves the transmission of bedside ultrasound (US) images with direct feedback from an US expert. In this review, we summarize the current uses of real-time TUS and discuss its potential future uses. Methods: We performed a literature search (PubMed and EMBase) to assess articles related to real-time TUS. Data were extracted using a standardized collection form, and relevant articles were separated into feasibility or clinical studies. Results: Our search yielded 45 articles, with most of the reports taking place in resource-constrained settings. A large portion of the studies discussed the use of the focused assessment with sonography in trauma exam. Others included musculoskeletal, vascular, and echocardiography. Conclusion: Real-time TUS allows for rapid access to diagnostic imaging in various clinical settings. This technology is poised to expand with many uses on the horizon.

Use of targeted memory reactivation enhances skill performance during a nap and enhances declarative memory during wake in healthy young adults.

Sleep is an important component of motor memory consolidation and learning, providing a critical tool to enhance training and rehabilitation. Following initial skill acquisition, memory consolidation is largely a result of non-rapid eye movement sleep over either a full night or a nap. Targeted memory reactivation is one method used to enhance this critical process, which involves the pairing of an external cue with task performance at the time of initial motor skill acquisition, followed by replay of the same cue during sleep. Application of targeted memory reactivation during sleep leads to increased functional connectivity within task-related brain networks and improved behavioural performance in healthy young adults. We have previously used targeted memory reactivation throughout the first two slow-wave sleep cycles of a full night of sleep to enhance non-dominant arm throwing accuracy in healthy young adults. Here, we aimed to determine whether application of targeted memory reactivation throughout a 1-hr daytime nap was sufficient to enhance performance on the same non-dominant arm throwing task in healthy young adults. Participants were allocated to either nap or no nap, and within those groups half received targeted memory reactivation throughout a 1-hr between-session period, leading to four groups. Only participants who slept between sessions while receiving targeted memory reactivation enhanced their throwing accuracy upon beginning the second session. Future studies will aim to use this technique as an adjunct to traditional physical rehabilitation with individuals with neurologic diagnoses such as stroke.

Numeracy and Interpretation of Prognostic Estimates in Intracerebral Hemorrhage Among Surrogate Decision Makers in the Neurologic ICU.

OBJECTIVE: Clinicians caring for patients with intracerebral hemorrhage must often discuss prognosis and goals of care with their patients' surrogate decision makers, and may make numeric estimates of likelihood of survival and functional independence, informed by validated prediction models. Surrogates' prognostic estimates are often discordant with physicians', suggesting that physicians' numeric statements may not be accurately interpreted. We sought to assess the relationship between numeracy and interpretation of prognostic estimates in intracerebral hemorrhage among surrogate decision makers. We also assessed surrogates' application of prognostic estimates to decisions regarding goals of care. DESIGN: Single-center, survey-based, cross-sectional study. SETTING: Twenty-two-bed neurologic ICU at an urban, academic hospital. SUBJECTS: Surrogate decision makers for patients admitted to the neurologic ICU. INTERVENTIONS: Participants completed a survey containing five clinical vignettes describing patients with nontraumatic intracerebral hemorrhage. For each patient, numerical estimates of survival and functional independence were explicitly provided, based on the validated outcome risk stratification scale (intracerebral hemorrhage score) and the Prediction of Functional Outcome in Patients with Primary Intracerebral Hemorrhage score. MEASUREMENTS AND MAIN RESULTS: Participants were asked to make their own prognostic estimates, as well as to describe their preferred goals of care for each hypothetical patient. Respondent demographics were collected, and numeracy was assessed using a modified Lipkus 11-item scale. Poor numeracy was common (42 of 96 total subjects) in this relatively highly educated population. Most prognostic estimates (55%) made by surrogates were discordant with the provided estimates. High numeracy correlated with better concordance (odds ratio, 23.9 [5.57-97.64]; p < 0.001), independent of several factors, including level of education and religion. Numeracy also affected goals-of-care decisions made by surrogates. CONCLUSIONS: Poor numeracy is common among surrogate decision makers in an intensive care setting and poses a barrier to communication between surrogates and clinicians regarding prognosis and goals of care.

Pilot Feasibility Study of Therapeutic Hypothermia for Moderate to Severe Acute Respiratory Distress Syndrome.

OBJECTIVES: Prior studies suggest hypothermia may be beneficial in acute respiratory distress syndrome, but cooling causes shivering and increases metabolism. The objective of this study was to assess the feasibility of performing a randomized clinical trial of hypothermia in patients with acute respiratory distress syndrome receiving treatment with neuromuscular blockade because they cannot shiver. DESIGN: Retrospective study and pilot, prospective, open-label, feasibility study. SETTING: Medical ICU. PATIENTS: Retrospective review of 58 patients with acute respiratory distress syndrome based on Berlin criteria and PaO2/FIO2 less than 150 who received neuromuscular blockade. Prospective hypothermia treatment in eight acute respiratory distress syndrome patients with PaO2/FIO2 less than 150 receiving neuromuscular blockade. INTERVENTION: Cooling to 34-36°C for 48 hours. MEASUREMENTS AND MAIN RESULTS: Core temperature, hemodynamics, serum glucose and electrolytes, and P/F were sequentially measured, and medians (interquartile ranges) presented, 28-day ventilator-free days, and hospital mortality were calculated in historical controls and eight cooled patients. Average patient core temperature was 36.7°C (36-37.3°C), and fever occurred during neuromuscular blockade in 30 of 58 retrospective patients. In the prospectively cooled patients, core temperature reached target range less than or equal to 4 hours of initiating cooling, remained less than 36°C for 92% of the 48 hours cooling period without adverse events, and was lower than the controls (34.35°C [34-34.8°C]; p < 0.0001). Compared with historical controls, the cooled patients tended to have lower hospital mortality (75% vs 53.4%; p = 0.26), more ventilator-free days (9 [0-21.5] vs 0 [0-12]; p = 0.16), and higher day 3 P/F (255 [160-270] vs 171 [120-214]; p = 0.024). CONCLUSIONS: Neuromuscular blockade alone does not cause hypothermia but allowed acute respiratory distress syndrome patients to be effectively cooled. Results support conducting a randomized clinical trial of hypothermia in acute respiratory distress syndrome and the feasibility of studying acute respiratory distress syndrome patients receiving neuromuscular blockade.

NEU1 Sialidase Regulates Membrane-tethered Mucin (MUC1) Ectodomain Adhesiveness for Pseudomonas aeruginosa and Decoy Receptor Release.

Airway epithelia express sialylated receptors that recognize exogenous danger signals. Regulation of receptor responsiveness to these signals remains incompletely defined. Here, we explore the mechanisms through which the human sialidase, neuraminidase-1 (NEU1), promotes the interaction between the sialoprotein, mucin 1 (MUC1), and the opportunistic pathogen, Pseudomonas aeruginosa. P. aeruginosa flagellin engaged the MUC1 ectodomain (ED), increasing NEU1 association with MUC1. The flagellin stimulus increased the association of MUC1-ED with both NEU1 and its chaperone/transport protein, protective protein/cathepsin A. Scatchard analysis demonstrated NEU1-dependent increased binding affinity of flagellin to MUC1-expressing epithelia. NEU1-driven MUC1-ED desialylation rapidly increased P. aeruginosa adhesion to and invasion of the airway epithelium. MUC1-ED desialylation also increased its shedding, and the shed MUC1-ED competitively blocked P. aeruginosa adhesion to cell-associated MUC1-ED. Levels of desialylated MUC1-ED were elevated in the bronchoalveolar lavage fluid of mechanically ventilated patients with P. aeruginosa airway colonization. Preincubation of P. aeruginosa with these same ex vivo fluids competitively inhibited bacterial adhesion to airway epithelia, and MUC1-ED immunodepletion completely abrogated their inhibitory activity. These data indicate that a prokaryote, P. aeruginosa, in a ligand-specific manner, mobilizes eukaryotic NEU1 to enhance bacterial pathogenicity, but the host retaliates by releasing MUC1-ED into the airway lumen as a hyperadhesive decoy receptor.

The NEU1-selective sialidase inhibitor, C9-butyl-amide-DANA, blocks sialidase activity and NEU1-mediated bioactivities in human lung in vitro and murine lung in vivo.

Neuraminidase-1 (NEU1) is the predominant sialidase expressed in human airway epithelia and lung microvascular endothelia where it mediates multiple biological processes. We tested whether the NEU1-selective sialidase inhibitor, C9-butyl-amide-2-deoxy-2,3-dehydro-N-acetylneuraminic acid (C9-BA-DANA), inhibits one or more established NEU1-mediated bioactivities in human lung cells. We established the IC50 values of C9-BA-DANA for total sialidase activity in human airway epithelia, lung microvascular endothelia and lung fibroblasts to be 3.74 µM, 13.0 µM and 4.82 µM, respectively. In human airway epithelia, C9-BA-DANA dose-dependently inhibited flagellin-induced, NEU1-mediated mucin-1 ectodomain desialylation, adhesiveness for Pseudomonas aeruginosa and shedding. In lung microvascular endothelia, C9-BA-DANA reversed NEU1-driven restraint of cell migration into a wound and disruption of capillary-like tube formation. NEU1 and its chaperone/transport protein, protective protein/cathepsin A (PPCA), were differentially expressed in these same cells. Normalized NEU1 protein expression correlated with total sialidase activity whereas PPCA expression did not. In contrast to eukaryotic sialidases, C9-BA-DANA exerted far less inhibitory activity for three selected bacterial neuraminidases (IC50 > 800 µM). Structural modeling of the four human sialidases and three bacterial neuraminidases revealed a loop between the seventh and eighth strands of the ß-propeller fold, that in NEU1, was substantially shorter than that seen in the six other enzymes. Predicted steric hindrance between this loop and C9-BA-DANA could explain its selectivity for NEU1. Finally, pretreatment of mice with C9-BA-DANA completely protected against flagellin-induced increases in lung sialidase activity. Our combined data indicate that C9-BA-DANA inhibits endogenous and ectopically expressed sialidase activity and established NEU1-mediated bioactivities in human airway epithelia, lung microvascular endothelia, and fibroblasts in vitro and murine lungs in vivo.

Adapting the ABCDEF Bundle to Meet the Needs of Patients Requiring Prolonged Mechanical Ventilation in the Long-Term Acute Care Hospital Setting: Historical Perspectives and Practical Implications.

When robust clinical trials are lacking, clinicians are often forced to extrapolate safe and effective evidence-based interventions from one patient care setting to another. This article is about such an extrapolation from the intensive care unit (ICU) to the long-term acute care hospital (LTACH) setting. Chronic critical illness is an emerging, disabling, costly, and yet relatively silent epidemic that is central to both of these settings. The number of chronically critically ill patients requiring prolonged mechanical ventilation is expected to reach unprecedented levels over the next decade. Despite the prevalence, numerous distressing symptoms, and exceptionally poor outcomes associated with chronic critical illness, to date there is very limited scientific evidence available to guide the care and management of this exceptionally vulnerable population, particularly in LTACHs. Recent studies conducted in the traditional ICU setting suggest interprofessional, multicomponent strategies aimed at effectively assessing, preventing, and managing pain, agitation, delirium, and weakness, such as the ABCDEF bundle, may play an important role in the recovery of the chronically critically ill. This article reviews what is known about the chronically critically ill, provide readers with some important historical perspectives on the ABCDEF bundle, and address some controversies and practical implications of adopting the ABCDEF bundle into the everyday care of patients requiring prolonged mechanical ventilation in the LTACH setting. We believe developing new and better ways of addressing both the science and organizational aspects of managing the common and distressing symptoms associated with chronic critical illness and prolonged mechanical ventilation will ultimately improve the quality of life for the many patients and families admitted to LTACHs annually.

Diagnostic value of pleural fluid obtained from a chest tube collection system.

BACKGROUND: Pleural fluid is typically drawn directly from the pleural space for diagnostic studies, but occasionally analyses are desired when a chest tube is already in place and a traditional approach is not feasible. The diagnostic value of analyzing fluid samples obtained from the pleural fluid collection system after chest tube insertion is unknown. METHODS: We performed a prospective observational study of patients in whom chest tube placement was planned for clinical indications. Diagnostic studies were performed on fluid obtained from the pleural space at the time of tube insertion and then repeated 2, 6, and 24 h later on samples obtained from the fluid collection system. RESULTS: Fifty-five percent of the 23 effusions studied met light's criteria for exudate at baseline. Lactate dehydrogenase (LDH) varied considerably over time from baseline measures with only 25 % of measures at 24 h falling within 25 % of baseline levels. The sensitivity for exudate by LDH remained 100 % with poor specificity ranging 50-69 % with repeat measures. Total protein exhibited less variability with 85 % of measures at 24 h falling within 25 % of baseline measure. Sensitivity and specificity at 24 h were 88 and 82 %, respectively. Repeat measures of cholesterol, albumin, and triglycerides generally correlated well (Spearman's rho > 0.90) with baseline values. Measures of glucose and cell counts varied considerably from baseline. CONCLUSIONS: Analysis of pleural fluid from a chest tube collection system is feasible and can provide useful diagnostic information. Practitioners should consider the test characteristics of each measure when interpreting samples obtained.

Early In-Bed Cycle Ergometry in Mechanically Ventilated Patients.

BACKGROUND: Critical illness requiring invasive mechanical ventilation can precipitate important functional disability, contributing to multidimensional morbidity following admission to an intensive care unit (ICU). Early in-bed cycle ergometry added to usual physiotherapy may mitigate ICU-acquired physical function impairment. METHODS: We randomly assigned 360 adult ICU patients undergoing invasive mechanical ventilation to receive 30 minutes of early in-bed Cycling + Usual physiotherapy (n=178) or Usual physiotherapy alone (n=182). The primary outcome was the Physical Function ICU Test-scored (PFIT-s) at 3 days after discharge from the ICU (the score ranges from 0 to 10, with higher scores indicating better function). RESULTS: Cycling began within a median (interquartile range) of 2 (1 to 3) days of starting mechanical ventilation; patients received 3 (2 to 5) cycling sessions for a mean (±standard deviation) of 27.2 ± 6.6 minutes. In both groups, patients started Usual physiotherapy within 2 (2 to 4) days of mechanical ventilation and received 4 (2 to 7) Usual physiotherapy sessions. The duration of Usual physiotherapy was 23.7 ± 15.1 minutes in the Cycling + Usual physiotherapy group and 29.1 ± 13.2 minutes in the Usual physiotherapy group. No serious adverse events occurred in either group. Among survivors, the PFIT-s at 3 days after discharge from the ICU was 7.7 ± 1.7 in the Cycling + Usual physiotherapy group and 7.5 ± 1.7 in the Usual physiotherapy group (absolute difference, 0.23 points; 95% confidence interval, -0.19 to 0.65; P=0.29). CONCLUSIONS: Among adults receiving mechanical ventilation in the ICU, adding early in-bed Cycling to usual physiotherapy did not improve physical function at 3 days after discharge from the ICU compared with Usual physiotherapy alone. Cycling did not cause any serious adverse events. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov numbers, NCT03471247 [full randomized clinical trial] and NCT02377830 [CYCLE Vanguard 46-patient internal pilot].).

Disseminated Cryptococcosis in an Immunocompromised Patient with Altered Mental Status and a Lung Nodule.

Introduction: Disseminated cryptococcosis is an opportunistic infection that commonly affects the central nervous and respiratory systems and is often fatal in immunocompromised host patients. Diagnosing disseminated cryptococcosis is challenging at times due to the nonspecific presentation, resulting in delayed treatment and increased mortality. Case presentation: A 48-year-old man presented with altered mental status and shortness of breath requiring intubation. Medical history was significant for rheumatoid arthritis, diabetes mellitus, chronic kidney disease, sarcoidosis, and polymyalgia rheumatica. Home medications included prednisone, methotrexate, and tocilizumab. Computed tomography chest revealed multifocal pneumonia with a cavitary nodule with halo sign. One week after extubation, the patient remained confused. Lumbar puncture (LP) was positive for Cryptococcus neoformans within 5 days. Bronchoalveolar lavage (BAL) yielded similar results on fungal culture one month later. Conclusion: An immunocompromised host patient who presents with altered mental status with concomitant lung nodules should have disseminated cryptococcosis as a differential diagnosis. CT chest commonly demonstrate peripheral lung nodules with cavitation, air bronchograms, halo sign, and/or enlarged mediastinal lymphadenopathy, as found in our patient. If the clinical suspicion for disseminated cryptococcosis is high, an LP should be performed, as BAL results may often be delayed since Cryptococcus grows slowly from the lungs. Empiric antifungals should be started immediately, given increased mortality if treatment is delayed.

Combining exercise, protein supplementation and electric stimulation to mitigate muscle wasting and improve outcomes for survivors of critical illness-The ExPrES study.

BACKGROUND: Neuromuscular electrical stimulation (NMES) with high protein supplementation (HPRO) to preserve muscle mass and function has not been assessed in ICU patients. We compared the effects of combining NMES and HPRO with mobility and strength rehabilitation (NMES+HPRO+PT) to standardized ICU care. OBJECTIVES: To assess the effectiveness of combined NMES+HPRO+PT in mitigating sarcopenia as evidenced by CT volume and cross-sectional area when compared to usual ICU care. Additionally, we assessed the effects of the combined therapy on select clinical outcomes, including nutritional status, nitrogen balance, delirium and days on mechanical ventilation. METHODS: Participants were randomized by computer generated assignments to receive either NMES+HPRO+PT or standard care. Over 14 days the standardized ICU care group (N = 23) received usual critical care and rehabilitation while the NMES+HPRO+PT group (N = 16) received 30 min neuromuscular electrical stimulation of quadriceps and dorsiflexors twice-daily for 10 days and mean 1.3 ± 0.4 g/kg body weight of high protein supplementation in addition to standard care. Nonresponsive participants received passive exercises and, once responsive, were encouraged to exercise actively. Primary outcome measures were muscle volume and cross-sectional area measured using CT-imaging. Secondary outcomes included nutritional status, nitrogen balance, delirium and days on mechanical ventilation. RESULTS: The NMES+HPRO+PT group (N = 16) lost less lower extremity muscle volume compared to the standard care group (N = 23) and had larger mean combined thigh cross-sectional area. The nitrogen balance remained negative in the standard care group, while positive on days 5, 9, and 14 in the NMES+HPRO+PT group. Standard care group participants experienced more delirium than the NMES+HPRO+PT group. No differences between groups when comparing length of stay or mechanical ventilation days. CONCLUSIONS: The combination of neuromuscular electrical stimulation, high protein supplementation and mobility and strength rehabilitation resulted in mitigation of lower extremity muscle loss and less delirium in mechanically ventilated ICU patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02509520. Registered July 28, 2015.

Guillain-Barre syndrome secondary to COVID-19 infection: A case report.

Guillain-Barre syndrome (GBS) is a rare autoimmune disease that often manifests as a post-viral complication. However, its association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. We present a rare case of GBS secondary to COVID-19 infection complicated by rapidly progressive sensorimotor deterioration resistant to plasma exchange therapy.

Severity-of-Illness Scores and Discharge Disposition in Patients Admitted to Long-Term Acute Care Hospitals.

BACKGROUND: After an intensive care unit (ICU) admission, nearly 20% of survivors of chronic critical illness require admission to a long-term acute care hospital (LTACH) for continued subspecialty care. The effect of the burden of medical comorbidities on discharge disposition after LTACH admission remains unclear. METHODS: A retrospective cohort study was performed involving patients with chronic critical illness who were discharged from the medical ICU and admitted to an LTACH between 2016 and 2018. The patients' Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), Nutrition Risk in the Critically Ill (NUTRIC), and Charlson Comorbidity Index (CCI) scores at the time of LTACH admission were calculated from electronic medical records. The mean scores on each instrument were compared by discharge disposition. RESULTS: A total of 156 patients were admitted to the LTACH from the medical ICU between 2016 and 2018. They had a mean (SD) age of 61.5 (13.3) years, a mean (SD) body mass index of 28.1 (8.3), a median (IQR) ICU stay of 16.3 (1-108) days, and a median (IQR) LTACH stay of 38.2 (1-227) days. Patients who were discharged home had lower mean (SD) APACHE II (14.6 [5.0] vs 18.2 [5.4], P = .01), SOFA (3.3 [2.1] vs 4.6 [2.1], P = .03), NUTRIC (3.3 [1.4] vs 4.6 [1.4], P = .001), and CCI (4.3 [2.5] vs 6.1 [2.8], P = .02) scores on admission to the LTACH than those who were not discharged home. CONCLUSION: Severity-of-illness scores on admission to an LTACH can be used to predict patients' likelihood of being discharged home.

A case of fatal disseminated adenovirus and drug-resistant Pneumocystis pneumonia in a patient who received chemotherapy for mantle cell lymphoma.

Adenovirus (ADV) may cause severe complications in hematopoietic stem cell transplant recipients, but disseminated ADV infections in patients who received chemotherapy alone for hematological malignancies are poorly understood due to the rarity of cases. Concomitant infection with Pneumocystis (PCP) is extremely rare. Despite being diagnostically challenging, a more specific workup needs to be initiated with a low threshold in patients who are exposed to agents with the potential to suppress T cells. We report a fatal case of disseminated ADV and drug-resistant PCP pneumonia in a patient with mantle cell lymphoma who had only received combination chemotherapy. A 75-year-old man who was diagnosed with mantle cell lymphoma 10 months prior was admitted for mild hypoxic respiratory failure. Bendamustine, Rituximab, Cytarabine regimen had resulted in complete remission of his lymphoma, with the last cycle of chemotherapy administered 3 months prior to admission. CT of the chest revealed ground-glass opacities concerning pneumonia. Initial laboratory tests were remarkable for mild leukopenia. The respiratory viral panel was only positive for ADV. He did not respond to empiric antibiotics for community-acquired pneumonia and Trimethoprim / Sulfamethoxazole given later for positive Beta D Glucan (BDG) suggestive of Pneumocystis pneumonia. Then, he developed hemorrhagic cystitis, followed by liver and renal function derangement that prompted checking serum ADV viral load by polymerase chain reaction (PCR). This test took 1 week to return, with a viral load of 50, 000 copies/mL suggesting disseminated ADV infection. Despite initiation of Cidofovir, multi-organ failure continued to progress, and the follow-up viral load had doubled on Day 2. The patient passed away the same day shortly after transition to comfort care. T cell suppression seems to be a risk factor for disseminated ADV disease. Clinicians may need to maintain a low threshold to send serum quantitative ADV PCR when symptoms are not improved by antimicrobial treatment for more conventional infections in patients who received agents that are known to suppress T cells, such as Bendamustine.

Critical Care Cycling to Improve Lower Extremity Strength (CYCLE): protocol for an international, multicentre randomised clinical trial of early in-bed cycling for mechanically ventilated patients.

INTRODUCTION: In-bed leg cycling with critically ill patients is a promising intervention aimed at minimising immobility, thus improving physical function following intensive care unit (ICU) discharge. We previously completed a pilot randomised controlled trial (RCT) which supported the feasibility of a large RCT. In this report, we describe the protocol for an international, multicentre RCT to determine the effectiveness of early in-bed cycling versus routine physiotherapy (PT) in critically ill, mechanically ventilated adults. METHODS AND ANALYSIS: We report a parallel group RCT of 360 patients in 17 medical-surgical ICUs and three countries. We include adults (≥18 years old), who could ambulate independently before their critical illness (with or without a gait aid), ≤4 days of invasive mechanical ventilation and ≤7 days ICU length of stay, and an expected additional 2-day ICU stay, and who do not fulfil any of the exclusion criteria. After obtaining informed consent, patients are randomised using a web-based, centralised system to either 30 min of in-bed cycling in addition to routine PT, 5 days per week, up to 28 days maximum, or routine PT alone. The primary outcome is the Physical Function ICU Test-scored (PFIT-s) at 3 days post-ICU discharge measured by assessors blinded to treatment allocation. Participants, ICU clinicians and research coordinators are not blinded to group assignment. Our sample size estimate was based on the identification of a 1-point mean difference in PFIT-s between groups. ETHICS AND DISSEMINATION: Critical Care Cycling to improve Lower Extremity (CYCLE) is approved by the Research Ethics Boards of all participating centres and Clinical Trials Ontario (Project 1345). We will disseminate trial results through publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03471247 (Full RCT); NCT02377830 (CYCLE Vanguard 46 patient internal pilot).