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.

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.

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.

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.

Predictive Biomarkers of Dyspnea Response to Dexamethasone and Placebo in Cancer Patients.

CONTEXT: In the Alleviating Breathlessness in Cancer Patients with Dexamethasone (ABCD) trial, dexamethasone did not improve dyspnea more than placebo in unselected cancer patients. However, it is unclear if patients with greater inflammation would be more likely to derive a treatment response. OBJECTIVES: To examine the predictive utility of cytokines for dyspnea response. METHODS: We performed a secondary analysis of the ABCD double-blind, randomized clinical trial comparing high-dose dexamethasone to placebo (NCT03367156). The primary outcome was dyspnea intensity over 14 days. Blood cytokine levels (TNF, IL-6, IL-8, and IL-10) were measured at baseline, day seven, and day 14. We used a generalized additive model to examine the association between baseline cytokine level and change in dyspnea from baseline to day seven and baseline to day 14 in dexamethasone and placebo groups. RESULTS: Of the 128 enrolled patients, 45 provided blood samples. TNF, IL-6, and IL-8 decreased over 14 days in the dexamethasone group but not placebo (P<0.05). Lower baseline TNF was associated with a greater reduction in dyspnea intensity by day seven in the placebo group (P=0.0013); conversely, higher baseline TNF was associated with a greater reduction in dyspnea intensity by day 7 in the dexamethasone group (difference between groups P=0.0019). Similar patterns were observed for IL-6 (P=0.000051), IL-8 (P=0.00063), and IL-10 (P=0.01) on day seven, and all cytokines on day 14. CONCLUSION: Cytokines decreased with dexamethasone, but not placebo. Higher baseline cytokine levels may identify patients likely to respond to dexamethasone and less likely to respond to placebo.

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.

Randomization for clinical research: an easy-to-use spreadsheet method.

In this article, we illustrate a new method for random selection and random assignment that we developed in a pilot study for a randomized clinical trial. The randomization database is supported by a commonly available spreadsheet. Formulas were written for randomizing participants and for creating a "shadow" system to verify integrity of the randomization. Advantages of this method are that it is easy to use, effective, and portable, allowing it to be shared among multiple investigators at multiple study sites. Clinical researchers may find the method useful for research projects that are pilot studies or conducted with limited funding.

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.

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.

Adverse hemodynamic effects of lateral rotation during mechanical ventilation.

Turning critically ill, mechanically ventilated patients every 2 hours is a fundamental nursing intervention to reduce the negative impact of prolonged immobility from preventable pulmonary complications such as ventilator-associated pneumonia and atelectasis. Unfortunately, when coupled with positive pressure ventilation, the benefits of turning may come at the expense of cardiovascular function. Clinicians should closely monitor the hemodynamic response to turning mechanically ventilated patients, and if compromise is observed, the degree and duration of compromise may provide guidance to the appropriate intervention.

Cosinor analysis for temperature time series data of long duration.

The application of cosinor models to long time series requires special attention. With increasing length of the time series, the presence of noise and drifts in rhythm parameters from cycle to cycle lead to rapid deterioration of cosinor models. The sensitivity of amplitude and model-fit to the data length is demonstrated for body temperature data from ambulatory menstrual cycling and menopausal women and from ambulatory male swine. It follows that amplitude comparisons between studies cannot be made independent of consideration of the data length. Cosinor analysis may be carried out on serial-sections of the series for improved model-fit and for tracking changes in rhythm parameters. Noise and drift reduction can also be achieved by folding the series onto a single cycle, which leads to substantial gains in the model-fit but lowers the amplitude. Central values of model parameters are negligibly changed by consideration of the autoregressive nature of residuals.

A pilot home study of temporal variations of symptoms in chronic obstructive lung disease.

The purposes of this pilot study are to describe the 24-hr patterns of dyspnea, fatigue, and peak expiratory flow rate (PEFR) in patients with chronic obstructive pulmonary disease (COPD) and examine their interrelationships. The repeated-measures design protocol involved 10 patients with moderate to severe COPD who self-assessed dyspnea, fatigue, and PEFR five times a day for 8 days. Circadian rhythms were documented by single cosinor analysis in 40% of the participants for dyspnea, 60% for fatigue, and 60% for PEFR. The 8-day, 24-hr means of dyspnea and fatigue were moderately correlated; 70% of the sample displayed significant correlations. The means of PEFR and both dyspnea and fatigue were weakly negatively correlated. The findings suggest that circadian rhythm in lung function may not be temporally coupled with the circadian rhythm in dyspnea and fatigue in all patients and that the mean self-perceived levels of dyspnea and fatigue are moderately related.

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.

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.

Circadian temperature rhythm of laboratory swine.

The circadian temperature rhythm (CTR) profile holds promise for monitoring the domestic pig's responses to stress and illness. In the present study we quantified the CTR profile of nine growing-finishing swine using a time-series, small-group design. Temperature was monitored using a probe implanted in the ear for 5 1/2 to 9 1/2 consecutive days while the unrestrained pigs were housed singly in pens. The dominant period of the temperature data was estimated with the autocorrelation function and then used in standard cosinor analysis to compute the amplitude (half of the distance between the highest and lowest value within the period), mesor (rhythm-adjusted mean), and acrophase (timing of the cosine maximum). To examine the effect of procedural stress on CTR, we compared data from the first 3 days with those from subsequent days. Eight of the nine (89%) pigs had CTR with a mean (+/- standard error) period of 23.6 (0.5) h, amplitude of 0.18 (0.02) degrees C, mesor of 38.7 (0.24) degrees C, and acrophase at 19:44 h. Mean mesor and acrophase were not different, but amplitude was lower (P = 0.03) during the first 3 days after instrumentation than during subsequent days. We conclude that: 1) laboratory-housed, unrestrained, growing-finishing swine have CTR; 2) our ear-based instrumentation protocol imposes acute stress as reflected in attenuated CTR amplitude during the first 3 days after instrumentation; and 3) CTR adaptation to stress appears to occur over time.