Endothelial-to-Mesenchymal Transition in Human and Murine Models of Congenital Diaphragmatic Hernia.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a complex congenital disorder, characterized by pulmonary hypertension (PH) and hypoplasia. PH secondary to CDH (CDH-PH) features devastating morbidity and mortality (25-30%) among neonates. An unmet need is determining mechanisms triggering CDH-PH to save infants. Prior data suggest abnormal remodeling of the pulmonary vascular extracellular matrix (ECM), presumed to be driven by endothelial-to-mesenchymal transition (EndoMT), hinders postnatal vasodilation and limits anti-PH therapy in CDH. There are limited data on the role of EndoMT in CDH-PH. METHODS: The purpose of the study was to investigate how EndoMT contributes to CDH-PH by identifying cells undergoing EndoMT noted by alpha smooth muscle actin (α-SMA) expression in human umbilical vein endothelial cells (HUVECs) and lung tissue obtained from murine pups using the nitrofen model. N = 8 CDH, N = 8 control HUVECs were stained for α-SMA and CD31 after being exposed for 24 h to TGFB, a known EndoMT promoter. N = 8 nitrofen, N = 8 control murine pup lungs were also stained for α-SMA and CD31. α-SMA and CD31 expression was quantified in HUVECs and murine tissue using Fiji imaging software and normalized to the total number of cells per slide noted by DAPI staining. RESULTS: CDH HUVECs demonstrated a 1.1-fold increase in α-SMA expression (p = 0.02). The murine model did not show statistical significance between nitrofen and control pup lungs; however, there was a 0.4-fold increase in α-SMA expression with a 0.8-fold decrease in CD31 expression in the nitrofen pup lungs when compared to controls. CONCLUSION: These results suggest that EndoMT could potentially play a role in the ECM remodeling seen in CDH-PH.

Effect of dexamethasone on dyspnoea in patients with cancer (ABCD): a parallel-group, double-blind, randomised, controlled trial.

BACKGROUND: Systemic corticosteroids are commonly prescribed for palliation of dyspnoea in patients with cancer, despite scarce evidence to support their use. We aimed to assess the effect of high-dose dexamethasone versus placebo on cancer-related dyspnoea. METHODS: The parallel-group, double-blind, randomised, controlled ABCD (Alleviating Breathlessness in Cancer Patients with Dexamethasone) trial was done at the at the University of Texas MD Anderson Cancer Center and the general oncology clinic at Lyndon B Johnson General Hospital (both in Houston, TX, USA). Ambulatory patients with cancer, aged 18 years or older, and with an average dyspnoea intensity score on an 11-point numerical rating scale (NRS; 0=none, 10=worst) over the past week of 4 or higher were randomly assigned (2:1) to receive dexamethasone 8 mg orally every 12 h for 7 days followed by 4 mg orally every 12 h for 7 days, or matching placebo capsules for 14 days. Pharmacists did permuted block randomisation with a block size of six, and patients were stratified by baseline dyspnoea score (4-6 vs 7-10) and study site. Patients, research staff, and clinicians were masked to group assignment. The primary outcome was change in dyspnoea NRS intensity over the past 24 h from baseline to day 7 (±2 days). Analyses were done by modified intention-to-treat (ie, including all patients who were randomly assigned and started the study treatment, regardless of whether they completed the study). Enrolment was stopped after the second preplanned interim analysis, when the futility criterion was met. This study is registered with ClinicalTrials.gov (NCT03367156) and is now completed. FINDINGS: Between Jan 11, 2018, and April 23, 2021, we screened 2867 patients, enrolled 149 patients, and randomly assigned 128 to dexamethasone (n=85) or placebo (n=43). The mean change in dyspnoea NRS intensity from baseline to day 7 (±2 days) was -1·6 (95% CI -2·0 to -1·2) in the dexamethasone group and -1·6 (-2·3 to -0·9) in the placebo group, with no significant between-group difference (mean 0 [95% CI -0·8 to 0·7]; p=0·48). The most common all-cause grade 3-4 adverse events were infections (nine [11%] of 85 patients in the dexamethasone group vs three [7%] of 43 in the placebo group), insomnia (seven [8%] vs one [2%]), and neuropsychiatric symptoms (three [4%] vs none [0%]). Serious adverse events, all resulting in hospital admissions, were reported in 24 (28%) of 85 patients in the dexamethasone group and in three (7%) of 43 patients in the placebo group. No treatment-related deaths occurred in either group. INTERPRETATION: High-dose dexamethasone did not improve dyspnoea in patients with cancer more effectively than placebo and was associated with a higher frequency of adverse events. These data suggest that dexamethasone should not be routinely given to unselected patients with cancer for palliation of dyspnoea. FUNDING: US National Cancer Institute.

Pressure Injury Link to Entropy of Abdominal Temperature.

This study examined the association between pressure injuries and complexity of abdominal temperature measured in residents of a nursing facility. The temperature served as a proxy measure for skin thermoregulation. Refined multiscale sample entropy and bubble entropy were used to measure the irregularity of the temperature time series measured over two days at 1-min intervals. Robust summary measures were derived for the multiscale entropies and used in predictive models for pressure injuries that were built with adaptive lasso regression and neural networks. Both types of entropies were lower in the group of participants with pressure injuries (n=11) relative to the group of non-injured participants (n=15). This was generally true at the longer temporal scales, with the effect peaking at scale τ=22 min for sample entropy and τ=23 min for bubble entropy. Predictive models for pressure injury on the basis of refined multiscale sample entropy and bubble entropy yielded 96% accuracy, outperforming predictions based on any single measure of entropy. Combining entropy measures with a widely used risk assessment score led to the best prediction accuracy. Complexity of the abdominal temperature series could therefore serve as an indicator of risk of pressure injury.

Development and Preliminary Psychometric Testing of the Drake Atrial Electrogram Assessment Survey: DAEGAS.

BACKGROUND: Critical care nurses who care for postoperative cardiac surgery patients need such specialty knowledge as atrial electrograms (AEGs). An inadequate audit trail exists for psychometric performance of instruments to measure knowledge of AEGs. OBJECTIVES: The aim of this study was to revise a previously tested instrument and assess evidence for content validity (content validity index), internal consistency (Cronbach α), and stability (correlation coefficient, r) reliability against the a priori criterion of 0.80. METHODS: The multiple-choice response, self-administered, paper-and-pencil instrument was revised to 20 items and named the Drake Atrial Electrogram Assessment Survey (DAEGAS). A panel of 6 AEG experts reviewed the DAEGAS for content validity evidence. The instrument was further revised to 19 items (13 knowledge and 6 AEG interpretation) and tested with 76 critical care nurses from the greater Houston metropolitan area. RESULTS: The content validity index was 0.93. Cronbach α was .51, and test-retest r was 0.74. Cronbach α increased to .60 and r was 0.73 with removal of 3 items: 2 items with a negative item-total correlation and 1 item that was transitioned to a sample question. DISCUSSION: Content validity evidence exceeded the a priori criterion. Internal consistency and stability reliability estimates did not meet the criterion, albeit the latter met the criterion recommended by psychometricians for a new instrument. Recommendations include further development of the DAEGAS to improve internal consistency estimates and testing for evidence of other forms of validity. Reliable and valid assessment of critical care nurse knowledge of AEGs will require improved psychometric performance of the DAEGAS.

Survey of Nurses' Experiences Applying The Joint Commission's Medication Management Titration Standards.

BACKGROUND: Critical care nurses titrate continuous infusions of medications to achieve clinical end points. In 2017, The Joint Commission (TJC) placed restrictions on titration practice, decreasing nurses' autonomous decision-making. OBJECTIVES: To describe the practice and perceptions of nurses regarding the 2017 TJC accreditation/regulatory standards for titration of continuous medication infusions. METHODS: A survey of nurses' experiences titrating continuous medication infusions was developed, validated, and distributed electronically to members of the American Association of Critical-Care Nurses. RESULTS: The content validity index for the survey was 1.0 for relevance and 0.95 for clarity. A total of 781 nurses completed the survey; 625 (80%) perceived titration standards to cause delays in patient care, and 726 (93%) experienced moral distress (mean [SD], 4.97 [2.67]; scale, 0-10). Among respondents, 33% could not comply with titration orders, 68% reported suboptimal care resulting from pressure to comply with orders, 70% deviated from orders to meet patient needs, and 84% requested revised orders to ensure compliance. Suboptimal care and delays in care significantly and strongly (regression coefficients ≥0.69) predicted moral distress. CONCLUSIONS: Critical care nurses perceive TJC medication titration standards to adversely impact patient care and contribute to moral distress. The improved 2020 updates to the standards do not address delays and inability to comply with orders, leading to moral distress. Advocacy is indicated in order to mitigate unintended consequences of TJC medication management titration standards.

Comparison of Psychological and Physiological Stress in NICU Nurses: Effects of Unit Design and Shift.

BACKGROUND: Effects of unit design and shift worked on stress in neonatal intensive care unit (NICU) nurses have not been fully studied. PURPOSE: To compare stress in NICU nurses who work in single-family room (SFR) or open bay (OBY) units and on nonrotating day or night shift. METHODS: Full-time registered nurses (RNs) (n = 72) from a 42-bed SFR and a 131-bed OBY NICU participated in this comparative cross-sectional study. The Nurse Stress Scale (NSS) and within-shift repeated salivary cortisol levels were used to measure stress. The relationship between NSS score and salivary cortisol level was examined using multiple linear regression. Salivary cortisol levels of day versus night shift were compared with mixed-effects linear models. RESULTS: NSS scores were similar for SFR and OBY units (P = .672) and day versus night shift (P = .606). Changes in cortisol level over time (P = .764) and final cortisol level (P = .883) for SFR versus OBY were not significantly different after controlling for shift. Salivary cortisol level of day-shift nurses decreased significantly over time compared with night-shift nurses (P < .001). The final cortisol level was significantly higher for night-shift compared with day-shift nurses (P < .001). IMPLICATIONS FOR PRACTICE: Psychological (NSS) and physiologic (salivary cortisol) stress of NICU nurses is similar in established SFR and OBY units. Cortisol levels are higher at the end of shift in nurses who work night shift and may reflect increased physiologic stress. IMPLICATIONS FOR RESEARCH: Strategies are needed for reducing stress in NICU nurses who work night shift.

Blood biomarkers for physical recovery in ischemic stroke: a systematic review.

Stroke is a common cause of physical disability. Biomarkers have been used to predict prognosis in ischemic stroke, but studies linking biomarkers to physical recovery from ischemic stroke have not been systematically evaluated since 2011. The purpose of this paper is to report the findings of a systematic review of the intervening literature to identify potential predictive biomarkers for recovery of physical function following ischemic stroke. The PubMed, Embase, and CINAHL databases were searched for studies reported between January 1, 2011, and September 18, 2018. Search criteria were adult ischemic stroke patients, blood sample collection within 24 ± 6 hrs of stroke onset, and outcome measures, including physical function. Identified from 18 studies and representing four biological classifications, 34 biomarkers were significantly associated with physical recovery after ischemic stroke: (1) immune response (15, 44%); (2) lipids/metabolism (4, 12%); (3) neuronal function (4, 12%); and (4) blood vessel/circulation (11, 32%). Of the predictive biomarkers associated with 1-month recovery, 60% (6 of 10) was classified into blood vessel/circulation; 54% (14 of 26) of the biomarkers associated with 3-6 month physical recovery involved the immune response. Blood biomarkers might provide useful information to improve the prediction of physical outcome after ischemic stroke. The data suggest that biomarkers from four biological classifications may predict physical recovery in patients after ischemic stroke.

Psychometric Performance of the Arabic Versions of the Cancer Behavior Inventory-Brief and the Functional Assessment of Cancer Therapy-Breast.

BACKGROUND: Valid and reliable instruments in Arabic are needed to measure self-efficacy and quality of life for Arabic patients with cancer. OBJECTIVE: The aim of this study was to test the psychometric performance of the Cancer Behavior Inventory-Brief Arabic (CBI-BA), including participant understanding of items, and the Functional Assessment of Cancer Therapy-Breast Arabic (FACT-BA). METHODS: Using a cross-sectional design, 438 cancer patients completed the CBI-BA, 30 of whom completed cognitive interviews. A subsample 167 women with breast cancer also completed the FACT-BA. Internal consistency evidence was assessed with Cronbach's α and construct validity with principal axis factoring. RESULTS: Internal consistency estimates were acceptable for the total CBI-BA (α = .81) and FACT-BA (α = .88) scales. Exploratory factor analyses showed evidence of construct validity for the CBI-BA; 1 factor was derived, compared with four in the original English version. Cognitive interviews indicated satisfactory patient understanding of CBI-BA items. The Arabic version of the general FACT-General scale had 4 factors according to expectation. CONCLUSION: The CBI-BA has adequate psychometric performance for the measurement of self-efficacy for coping with cancer in Arabic patients. The FACT-General Arabic has adequate evidence of reliability and validity for the measurement of quality of life in Arabic women with breast cancer. IMPLICATIONS FOR PRACTICE: The availability of culturally sensitive and psychometrically sound instruments for Arabic patients diagnosed with cancer should be valuable for healthcare clinicians and researchers to assess self-efficacy for coping with cancer and quality of life.

Respiratory Compromise as a New Paradigm for the Care of Vulnerable Hospitalized Patients.

Acute respiratory compromise describes a deterioration in respiratory function with a high likelihood of rapid progression to respiratory failure and death. Identifying patients at risk for respiratory compromise coupled with monitoring of patients who have developed respiratory compromise might allow earlier interventions to prevent or mitigate further decompensation. The National Association for the Medical Direction of Respiratory Care (NAMDRC) organized a workshop meeting with representation from many national societies to address the unmet needs of respiratory compromise from a clinical practice perspective. Respiratory compromise may arise de novo or may complicate preexisting lung disease. The group identified distinct subsets of respiratory compromise that present similar opportunities for early detection and useful intervention to prevent respiratory failure. The subtypes were characterized by the pathophysiological mechanisms they had in common: impaired control of breathing, impaired airway protection, parenchymal lung disease, increased airway resistance, hydrostatic pulmonary edema, and right-ventricular failure. Classification of acutely ill respiratory patients into one or more of these categories may help in selecting the screening and monitoring strategies that are most appropriate for the patient's particular pathophysiology. Standardized screening and monitoring practices for patients with similar mechanisms of deterioration may enhance the ability to predict respiratory failure early and prevent its occurrence.

Validation of Salivary Interleukin-6 and Tumor Necrosis Factor-Alpha of Healthy Adult Volunteers by Enzyme Immunoassay.

BACKGROUND: Despite the use of saliva with enzyme immunoassay (EIA) methods validated for use with blood to measure interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), there has been limited validation of saliva as a matrix for EIA of IL-6 and TNF-α. OBJECTIVES: The study aims were to (a) validate one vendor's commercially available EIAs for detecting IL-6 and TNF-α in saliva as an alternative matrix to blood and (b) test the long-term stability of EIA detection of IL-6 and TNF-α after 12-month storage of saliva and plasma. METHODS: Spike and recovery and linearity experiments were performed. Concentrations of IL-6 and TNF-α in saliva and plasma from 20 healthy adult volunteers (6 men and 14 women) were correlated; the assays were repeated 12 months later. RESULTS: Spike and recovery and linearity performance was adequate for salivary IL-6: intra-assay percentage coefficient of variation, less than or equal to 8.4%; sensitivity, 0.11 pg/ml; mean recoveries, 81% in spiked saliva and 110% in spiked controls; and linearity, r = .995. The association between IL-6 in saliva and plasma was moderate and significant (p = .04). Spike and recovery and linearity performance was inadequate for TNF-α: intra-assay coefficient of variation, 10.8%; sensitivity, 2.3 pg/ml; mean recoveries, 44% in spiked saliva and 92% in spiked controls; and linearity, r = .950. The association between TNF-α in saliva and plasma was low and insignificant. Plasma and saliva IL-6 levels were significantly higher (p < .0001), and plasma and saliva TNF-α levels were significantly lower (p < .0001) after 12-month storage of specimens. DISCUSSION: We concluded that (a) saliva can be used to assess IL-6, but not TNF-α, with an EIA validated for use with blood and (b) 12-month storage of plasma and saliva significantly changes the assay results. Validation of other EIAs would expand assay options for investigators.

Development of an Arabic Translation of the Cancer Behavior Inventory-Brief.

PURPOSE: The objective was to develop an Arabic version of the Cancer Behavior Inventory-Brief (CBI-B). METHODS: The CBI-B was translated into Arabic using two forward and back translations. A translation validity index (TVI) was computed from review by an expert panel. RESULTS: Both back translations had issues with word choice, grammar, and meaning, which were resolved by selecting items from each forward translation. Item TVI was 0.83-1.0, with an overall mean of 0.95. CONCLUSION: The Arabic version of the CBI-B (CBI-BA) has acceptable evidence of translation validity. Two rounds of forward and back translation of the CBI-BA were needed to ensure semantic equivalence of the CBI-BA with the original instrument. Further psychometric testing with cognitive interviewing is recommended.

Reliability Estimates for the Arabic Versions of the Cancer Behavior Inventory-Brief and the Functional Assessment of Cancer Therapy-Breast.

PURPOSE: The study aims were to (a) test reliability of the Arabic versions of the Cancer Behavior Inventory-Brief Arabic (CBI-BA) among patients diagnosed with any type of cancer and the Functional Assessment of Cancer Therapy-Breast (FACT-BA) in women with breast cancer and (b) assess participant understanding of CBI-BA items. METHODS: A cross-sectional design was used to assess preliminary evidence for internal consistency reliability of the CBI-BA and the FACT-BA in a community-dwelling sample of Arabicspeaking persons diagnosed with cancer. Participants were randomly selected for cognitive interview. RESULTS: Cronbach's alphas were ≥.76 for the CBI-BA, .91 for the FACT-BA, and .43-.89 for the FACT-BA subscales. Cognitive interviews revealed several CBI-BA items required revision. CONCLUSION: The total CBI-BA and the FACT-BA scales have adequate internal consistency reliability estimates.

The Utility of the Swine Model to Assess Biological Rhythms and Their Characteristics during Different Stages of Residence in a Simulated Intensive Care Unit: A Pilot Study.

The purpose of this pilot study was to explore the utility of the mammalian swine model under simulated intensive care unit (sICU) conditions and mechanical ventilation (MV) for assessment of the trajectory of circadian rhythms of sedation requirement, core body temperature (CBT), pulmonary mechanics (PM) and gas exchange (GE). Data were collected prospectively with an observational time-series design to describe and compare circadian rhythms of selected study variables in four swine mechanically ventilated for up to seven consecutive days. We derived the circadian (total variance explained by rhythms of τ between 20 and 28 h)/ultradian (total variance explained by rhythms of τ between 1 and <20 h) bandpower ratio to assess the robustness of circadian rhythms, and compare findings between the early (first 3 days) and late (subsequent days) sICU stay. All pigs exhibited statistically significant circadian rhythms (τ between 20 and 28 h) in CBT, respiratory rate and peripheral oxygen saturation, but circadian rhythms were detected less frequently for sedation requirement, spontaneous minute volume, arterial oxygen tension, arterial carbon dioxide tension and arterial pH. Sedation did not appear to mask the circadian rhythms of CBT, PM and GE. Individual subject observations were more informative than group data, and provided preliminary evidence that (a) circadian rhythms of multiple variables are lost or desynchronized in mechanically ventilated subjects, (b) robustness of circadian rhythm varies with subject morbidity and (c) healthier pigs develop more robust circadian rhythm profiles over time in the sICU. Comparison of biological rhythm profiles among sICU subjects with similar severity of illness is needed to determine if the results of this pilot study are reproducible. Identification of consistent patterns may provide insight into subject morbidity and timing of such therapeutic interventions as weaning from MV.

Hemodynamic changes with manual and automated lateral turning in patients receiving mechanical ventilation.

BACKGROUND: Lateral turning of critical care patients receiving mechanical ventilation can adversely affect hemodynamic status. OBJECTIVE: To study hemodynamic responses to lateral turning. METHOD: A time-series design with automated signal processing and ensemble averaging was used to evaluate changes in heart rate, mean arterial pressure, and pulse pressure due to lateral turning in 13 adult medical-surgical critical care patients receiving mechanical ventilation. Patients were randomly assigned to the manual-turn or the automated-turn protocol for up to 7 consecutive days. Heart rate and arterial pressure were measured every 6 seconds for more than 24 hours, and pulse pressure was computed. RESULTS: A total of 6 manual-turn patients and 7 automated-turn patients completed the study. Statistically significant changes in heart rate, mean arterial pressure, and pulse pressure occurred with the manual turn. Return of the hemodynamic variables to baseline values required up to 45 minutes in the manual-turn patients (expected recovery time ≤ 5 minutes). However, clinically important changes dissipated within 15 minutes of the lateral turn. The steady-state heart rate response on the right side was slightly greater (3 beats per minute) than that on the back (P = .003). Automated turning resulted in no clinically important changes in any of the 3 variables. CONCLUSIONS: In medical-surgical critical care patients receiving mechanical ventilation, manual lateral turning was associated with changes in heart rate, mean arterial pressure, and pulse pressure that persisted up to 45 minutes.

Manual vs automated lateral rotation to reduce preventable pulmonary complications in ventilator patients.

PURPOSE: To estimate effect sizes for a trial to compare preventable pulmonary complications (PPCs), turning-related adverse events, mechanical ventilation duration, intensive care unit (ICU) length of stay, and ICU mortality between patients randomized to 2-hourly manual or continuous automated lateral rotation. METHODS: Randomized controlled trial pilot study with 15 patients selected randomly from eligible medical-surgical ICU patients from 2 tertiary hospitals and assigned randomly to the manual-turn or automated-turn protocol for up to 7 consecutive days. A radiologist blinded to group and site assessed serial chest radiographs for PPCs. Repeated-measures analysis with linear mixed models was used to estimate change in PPC score, and Wilcoxon rank sum or Fisher exact test was used to compare group differences in the secondary outcomes. RESULTS: Of 16 patients enrolled, 12 (75%) completed the study. Data from 15 patients, 7 manual turn and 8 automated turn, were analyzed. Between-group differences in PPC incidence (67% overall), change in PPC score (ß = 0.15, manual turn and ß = -0.44, automated turn), and secondary outcomes were not significant (P > .05). Standardized effect sizes were small to moderate for the outcome variables. A sample size of 54 patients would be needed to detect statistically significant between-group differences in PPC over time. CONCLUSIONS: The incidence of PPCs in adult patients receiving mechanical ventilation in a medical-surgical ICU was high. Automated turning decreased PPCs with time but had little effect on secondary outcomes. Safety outcomes were not substantially different between groups. A modest efficacy effect supported reduced PPCs with automated turning to the lateral position.

Microcirculatory oxygen transport and utilization.

The cardiovascular system (macrocirculation) circulates blood throughout the body, but the microcirculation is responsible for modifying tissue perfusion and adapting it to metabolic demand. Hemodynamic assessment and monitoring of the critically ill patient is typically focused on global measures of oxygen transport and utilization, which do not evaluate the status of the microcirculation. Despite achievement and maintenance of global hemodynamic and oxygenation goals, patients may develop microcirculatory dysfunction with associated organ failure. A thorough understanding of the microcirculatory system under physiologic conditions will assist the clinician in early recognition of microcirculatory dysfunction in impending and actual disease states.

Microcirculatory alterations in shock states.

Functional components of the microcirculation provide oxygen and nutrients and remove waste products from the tissue beds of the body's organs. Shock states overwhelmingly stress functional capacity of the microcirculation, resulting in microcirculatory failure. In septic shock, inflammatory mediators contribute to hemodynamic instability. In nonseptic shock states, the microcirculation is better able to compensate for alterations in vascular resistance, cardiac output, and blood pressure. Therefore, global hemodynamic and oxygen delivery parameters are appropriate for assessing, monitoring, and guiding therapy in hypovolemic and cardiogenic shock but, alone, are inadequate for septic shock.