Integrative literature review: Ethylene oxide exposure signs and symptoms.

BACKGROUND: Although ethylene oxide (EtO) gas is designated as a human carcinogen, extant literature reports mixed findings on the health effects of exposure. The disparate findings may reflect industry bias as many studies were funded by a large chemical industry lobby. OBJECTIVE: To conduct an integrative review of studies free from industry bias to facilitate compilation of a comprehensive list of reported signs and symptoms of EtO exposure. METHODS: We reviewed 1887 papers of which 42 articles met inclusion criteria. The authors conducted this review in accordance with PRISMA guidelines. The presence of bias was assessed using Joanna Briggs Institute checklists. RESULTS: Non-industry biased literature confirmed serious adverse health effects associated with EtO exposure at the occupational, hospital, and community level. EtO represents a carcinogen, neurotoxin, and respiratory irritant. CONCLUSION: After removal of industry-biased studies, EtO was unequivocally found to pose a threat to human health. There remains a gap in the number of studies examining community-level exposure, which is essential to understanding the impact of EtO. Given that EtO-emitting facilities are concentrated in diverse and disadvantaged communities, further study of EtO exposure health effects is warranted to inform public policy on toxic air emissions.

A novel administrative structure supporting academic nursing practice-based scholarship.

BACKGROUND: Practice-based scholarship (PBS) is critical for advancing nursing science, and for changing and saving lives. PURPOSE: The purpose of this paper is to share two major initiatives implemented at a Midwest College of Nursing (CON) to improve support for PBS. METHODS: The CON's Office of Research and Scholarship and Office of Faculty Practice were strategically redesigned to integrate and support practice scholarship across the CON. CONCLUSION: We share this example as a call to action and blueprint for other schools interested in elevating and advancing PBS.

Biopsychosocial Model of Traumatic Stress Symptoms in Women Experiencing Homelessness: A Qualitative Descriptive Study.

Trauma is nearly ubiquitous among women experiencing homelessness (WEH). WEH develop post-traumatic stress disorder (PTSD) at rates far exceeding the general population. The consequences of untreated PTSD can cascade, exacerbating existing physical, mental, and social health inequities, placing this population at risk for disproportionate biopsychosocial health adversity. Despite the outsized impact of PTSD, WEH are less likely to access or receive appropriate trauma-focused services. Understanding the unique and intersecting factors that contribute to the disproportionate PTSD toll on WEH may elucidate risk and protective factors, as well as possible intervention pathways to address the disparate trauma burden. This study employed a qualitative descriptive approach to develop understanding of the determinants of trauma risk, exposure, and outcomes among WEH. Semi-structured interviews were completed with 10 WEH, six shelter staff, four mental health professionals. Six deductively biopsychosocial model-derived themes were identified, alongside supporting categories. Themes/categories highlighted the role of biological, psychological, and socio-environmental determinants in shaping risk for and actualization of traumatic events and adverse outcomes. Trauma played an outsized role in shaping the health of WEH participants in this study, and the need for and interest in tailored trauma screening, treatment, psychoeducation options was highlighted. Recursive relationships between biopsychosocial determinants and trauma impact were identified. Participants emphasized population tailored trauma-focused interventions, specifically brief co-designed and community partner implemented interventions that address substance use behaviors, while leveraging the strengths of WEH. Addressing the marked trauma burden in WEH shows promise in promoting measurable biopsychosocial health improvements in this resilient yet overlooked population.

A review of clinical trials of advance care planning interventions adapted for limited health literacy.

OBJECTIVES: Advance care planning is vital for ensuring individuals receive end-of-life care that is consistent with their care preferences and improves patient quality of life and satisfaction with care; however, only 11% of Americans have discussed advance care planning with a healthcare provider. Individuals with limited health literacy are even less likely to participate in advance care planning due to difficulty comprehending complex health information. The purpose of this review was to identify randomized controlled trials designed to address the effects of limited health literacy on advance care planning, evaluate the quality of these studies, and summarize evaluation data to inform future studies. METHODS: This systematic review examined randomized controlled trials published from January 1997 to July 2020 using the PubMed, CINAHL, PsycINFO, and Scopus databases. Data were extracted and two reviewers independently evaluated the quality of studies using the Joanna Briggs Institute Critical Appraisal Tool. RESULTS: The database search yielded 253 studies and five studies were included in the final review. Studies were conducted in mostly White patients in outpatient clinics in the United States. Researchers wrote text at lower reading levels, added images to materials, and created videos to enhance communication. Health literacy interventions increased participant knowledge, preference for comfort care, engagement, and care documentation; however, several methodological issues were identified, including baseline differences in treatment and control groups, issues with blinding, lack of valid and reliable outcome measures, and inappropriate statistical analyses. SIGNIFICANCE OF RESULTS: More high-quality intervention studies that address the effects of limited health literacy on advance care planning in diverse populations and settings are needed. Future intervention studies should use reliable and valid instruments to measure advance care planning outcomes. Clinicians should use materials appropriate for their patients' health literacy levels to address their advance care planning needs.

Physical Activity and Cognitive Function in African American Older Adults Living With HIV.

The purpose of the current study was to investigate the association between self-reported physical activity (minutes/week) and cognitive functioning in a sample of African American older adults living with HIV. A secondary analysis of baseline data collected from clinically stable African American older adults living with HIV (aged >50 years; N = 124) enrolled in the Rush Center of Excellence on Disparities in HIV and Aging study was conducted. Participants completed a battery of 19 cognitive function tests that were used to create summary scores of global cognition and five cognitive domains. Physical activity was measured using a modified self-report questionnaire derived from a national health survey. Average self-reported number of weekly minutes spent in light physical activity was 290.6 minutes and for moderate/vigorous physical activity was 314.67 minutes. Number of weekly minutes of light physical activity was significantly positively associated with visuospatial ability; however, no associations were found between moderate/vigorous physical activity and any cognitive domain. Contrary to expectations, our findings do not support a relationship between moderate/vigorous physical activity and cognitive function in African American older adults living with HIV. [Journal of Gerontological Nursing, 47(12), 27-34.].

Mother's Own Milk Feeding and Severity of Respiratory Illness in Acutely Ill Children: An Integrative Review.

PROBLEM: Breastfed infants experience less severe infections while actively breastfeeding. However, little is known about whether a history of prior breastfeeding affects severity of illness. Therefore, the purpose of this integrative review was to examine the relationship between previous exposure to mother's own milk (MOM) feeding and severity of respiratory infectious illness in infants and children. ELIGIBILITY CRITERIA: Studies meeting the following criteria were included: human subjects, term birth, ages 0-35 months at time of study, diagnosis of pneumonia, bronchiolitis or croup, MOM feeding, and statistical analyses reporting separate respiratory infectious illness outcomes when combined with other infections. SAMPLE: Twelve articles met eligibility criteria. RESULTS: Major findings were inconsistent definitions of both dose and exposure period of breastfeeding and the severity of illness. In particular, the severity of illness measure was limited by the use of proxy variables such as emergency room visits or hospitalizations that lacked reliability and validity. However, given this limitation, the data suggested that exclusive breastfeeding for four to six months was associated with reduced severity of illness as measured by frequency of visits to the primary care provider office, emergency department or hospitalization. CONCLUSIONS: Future research in this area should incorporate reliable and valid measures of MOM dose and exposure period and severity of illness outcomes in the critically ill child. IMPLICATIONS: Among many positive outcomes associated with breastfeeding, an additional talking point for encouragement of exclusive breastfeeding for four to six months may be protective against severe respiratory infectious illness after cessation of breastfeeding.

Content validity testing of questions for a patient satisfaction with general anesthesia care instrument.

INTRODUCTION: Patient satisfaction with any health care experience is the result of a complex set of interactions between the patient and the health system in which care is received. Measuring patient satisfaction allows quantification of the congruence between the expectations of care and the care that is received. It is important to quantify satisfaction with care because it involves the patient in the care experience and decreases the potential gap between expected and actual care delivered over time. Despite the benefits of measuring satisfaction with anesthesia care, this outcome has been historically understudied possibly because of a lack of reliable tools that measure the construct. PURPOSE: The purpose of this study was to test the content validity of items derived from an integrated review of studies that measured patient satisfaction with anesthesia care. METHODS: The content validity of the questions was tested using an expert panel. A total of 13 nurse anesthetists consented to participate in the study as expert panel members. Each expert panel member evaluated the items for content validity on a 4-point scale. Both an Individual Content Validity Index (I-CVI) and a Scale Content Validity Index (S-CVI) were calculated. RESULTS: All I-CVI scores were greater than 0.8. The range of I-CVI was 0.833 to 1.0. The average scale Content Validity Index (S-CVI/ave) was 0.979. CONCLUSION: High content validity of all items was supported by an expert panel of anesthesia providers. The high level of agreement among raters related to the content of the general anesthesia statements supports progressing to the next step in instrument development.

Use of the Rasch model for initial testing of fit statistics and rating scale diagnosis for a general anesthesia satisfaction questionnaire.

BACKGROUND AND PURPOSE: The level of patient satisfaction is a result of a complex set of interactions between the patient and the health care provider. It is important to quantify satisfaction with care because it involves the patient in the care experience and decreases the potential gap between expected and actual care delivered. METHODS: We tested a preliminary 23-item instrument to measure patient satisfaction with general anesthesia care. The rating scale Rasch model was chosen as the framework. RESULTS: There were 10 items found to have sufficient evidence of stable fit statistics. Items included 2 questions related to information provided, 2 questions related to concern and kindness of the provider, and 1 question each for interpersonal skills of the provider, attention by the provider, feeling safe, well-being, privacy, and overall anesthesia satisfaction. CONCLUSION: Such actions as providing enough time to understand the anesthesia plan, answering questions related to the anesthetic, showing kindness and concern for the patient, displaying good interpersonal skills, providing adequate attention to the patient, providing a safe environment that maintains privacy and provides a sense of well-being are important actions that are well within the control of individual anesthesia providers and may lead to improved care from the perception of the patient.

Review of linear and nonlinear models in breath analysis by Cyranose 320.

Analysis of volatile organic compounds (VOCs) in breath specimens has potential for point of care (POC) screening due to ease of sample collection. While the electronic nose (e-nose) is a standard VOC measure across a wide range of industries, it has not been adopted for POC screening in healthcare. One limitation of the e-nose is the absence of mathematical models of data analysis that yield easily interpreted findings at POC. The purposes of this review were to (1) examine the sensitivity/specificity results from studies that analyzed breath smellprints using the Cyranose 320, a widely used commercial e-nose, and (2) determine whether linear or nonlinear mathematical models are superior for analyzing Cyranose 320 breath smellprints. This systematic review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses using keywords related to e-nose and breath. Twenty-two articles met the eligibility criteria. Two studies used a linear model while the rest used nonlinear models. The two studies that used a linear model had a smaller range for mean of sensitivity and higher mean (71.0%-96.0%;M= 83.5%) compared to the studies that used nonlinear models (46.9%-100%;M= 77.0%). Additionally, studies that used linear models had a smaller range for mean of specificity and higher mean (83.0%-91.5%;M= 87.2%) compared to studies that used nonlinear models (56.9%-94.0%;M= 76.9%). Linear models achieved smaller ranges for means of sensitivity and specificity compared to nonlinear models supporting additional investigations of their use for POC testing. Because our findings were derived from studies of heterogenous medical conditions, it is not known if they generalize to specific diagnoses.

The Versatility and Diagnostic Potential of VOC Profiling for Noninfectious Diseases.

A variety of volatile organic compounds (VOCs) are produced and emitted by the human body every day. The identity and concentration of these VOCs reflect an individual's metabolic condition. Information regarding the production and origin of VOCs, however, has yet to be congruent among the scientific community. This review article focuses on the recent investigations of the source and detection of biological VOCs as a potential for noninvasive discrimination between healthy and diseased individuals. Analyzing the changes in the components of VOC profiles could provide information regarding the molecular mechanisms behind disease as well as presenting new approaches for personalized screening and diagnosis. VOC research has prioritized the study of cancer, resulting in many research articles and reviews being written on the topic. This review summarizes the information gained about VOC cancer studies over the past 10 years and looks at how this knowledge correlates with and can be expanded to new and upcoming fields of VOC research, including neurodegenerative and other noninfectious diseases. Recent advances in analytical techniques have allowed for the analysis of VOCs measured in breath, urine, blood, feces, and skin. New diagnostic approaches founded on sensor-based techniques allow for cheaper and quicker results, and we compare their diagnostic dependability with gas chromatography- and mass spectrometry-based techniques. The future of VOC analysis as a clinical practice and the challenges associated with this transition are also discussed and future research priorities are summarized.

Parental Decision-Making for Surgery and Anesthesia in Young Children.

Millions of young children undergo surgery and anesthesia each year, yet there is a lack of scientific consensus about the safety of anesthesia exposure for the developing brain. Also poorly understood is parental anesthesia-related decision-making and how neurotoxicity information influences their choices. The theoretical model of parental decision-making generated in this research explicates this process. Interviews with 24 mothers yielded a theoretical framework based on their narratives developed using a qualitative grounded theory analysis. Five major themes emerged from these interviews: emotional processing, cognitive processing, relationships as resources, the mother/child dyad, and the health care context. Mothers described a non-linear, iterative process; they moved fluidly through emotional and cognitive processing supported by relationships as resources and influenced by the health care context. A key element was the subtheme of the medical translator, an individual who provided context and information. The mother/child dyad grounded the model in the relationship with the child.

Psychometric Testing of a Food Timing Questionnaire and Food Timing Screener.

BACKGROUND: Circadian rhythms coordinate multiple biological processes, and time of eating is an important entrainer of peripheral circadian clocks, including those in the gastrointestinal tract and liver. Whereas time of eating can be assessed through valid and reliable tools designed to measure nutrient intake (24-h recalls), currently there is no easily administered, valid, and reliable tool designed to specifically assess both time of food intake and sleep. OBJECTIVES: The objective of this study was to test the validity and reliability of 2 questionnaires developed to measure food and sleep-wake timing, the Food Timing Questionnaire (FTQ) and Food Timing Screener (FTS), and the agreement between these 2 tools. METHODS: The content validity of these tools was assessed by an expert panel of 10 registered dietitian nutritionists. Adult volunteers (n = 61) completed both tools to assess internal consistency and test-retest reliability. Criterion-related validity was determined through the association of FTQ and FTS with 2 valid instruments, the Automated Self-Administered 24-hour recall (ASA24®) Dietary Assessment tool and the Munich Chronotype Questionnaire. Agreement between the FTQ and FTS was tested by calculating the Pearson's correlations for both food and sleep-wake timing. RESULTS: The content validity indexes for both tools were >0.80, and internal consistency and test-retest reliability coefficients were >0.50 for all meals and sleep-wake times. Correlation coefficients were >0.40 between both tools and criterion measures of food intake and sleep except for snacks. Correlations between the FTQ and FTS for all eating events and sleep were >0.60 except for snack 1. CONCLUSIONS: Both the FTQ and FTS are valid and reliable instruments for meal timing and sleep. However, further psychometric testing in a more expansive and diverse sample will improve the ability of these tools to accurately assess food timing and sleep and their impact on health outcomes.

A Novel Affinity Engineered Anti-CD47 Antibody With Improved Therapeutic Index That Preserves Erythrocytes and Normal Immune Cells.

Therapeutic blockade of the CD47/SIRPα axis by small molecules or monoclonal antibodies (mAbs) is a proven strategy to enhance macrophages-mediated anti-tumor activity. However, this strategy has been hampered by elevated on-target toxicities and rapid clearance due to the extensive CD47 expression on normal cells ("antigen sink") such as red blood cells (RBCs). To address these hurdles, we report on the development of STI-6643, an affinity-engineered fully human anti-CD47 IgG4 antibody with negligible binding to normal cells. STI-6643 exhibited no hemagglutination activity on human RBCs at concentrations up to 300 µg/mL yet specifically blocked the CD47/SIPRα interaction. Of particular interest, STI-6643 preserved T cell functionality in vitro and showed significantly lower immune cell depletion in vivo in contrast to three previously published competitor reference anti-CD47 clones Hu5F9, AO-176 and 13H3. In cynomolgus monkeys, STI-6643 was well-tolerated at the highest dose tested (300 mg/kg/week) and provided favorable clinical safety margins. Finally, STI-6643 displayed comparable anti-tumor activity to the high-affinity reference clone Hu5F9 in a RAJI-Fluc xenograft tumor model as monotherapy or in combination with anti-CD20 (rituximab) or anti-CD38 (daratumumab) mAbs. These data suggest that STI-6643 possesses the characteristics of an effective therapeutic candidate given its potent anti-tumor activity and low toxicity profile.

The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation in Human Lung Cells and Inflammatory Cytokine Production in Human Lung and Intestinal Epithelial Cells.

The coronavirus disease 2019 (COVID-19) pandemic began in January 2020 in Wuhan, China, with a new coronavirus designated SARS-CoV-2. The principal cause of death from COVID-19 disease quickly emerged as acute respiratory distress syndrome (ARDS). A key ARDS pathogenic mechanism is the "Cytokine Storm", which is a dramatic increase in inflammatory cytokines in the blood. In the last two years of the pandemic, a new pathology has emerged in some COVID-19 survivors, in which a variety of long-term symptoms occur, a condition called post-acute sequelae of COVID-19 (PASC) or "Long COVID". Therefore, there is an urgent need to better understand the mechanisms of the virus. The spike protein on the surface of the virus is composed of joined S1-S2 subunits. Upon S1 binding to the ACE2 receptor on human cells, the S1 subunit is cleaved and the S2 subunit mediates the entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for the initiation and/or perpetuation of the cytokine storm. In this study, we tested the hypothesis that the S1 spike protein is sufficient to activate inflammatory signaling and cytokine production, independent of the virus. Our data support a possible role for the S1 spike protein in the activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 S1 spike protein in COVID-19 pathogenesis and PASC.

Policosanol for managing human immunodeficiency virus-related dyslipidemia in a medically underserved population: a randomized, controlled clinical trial.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with dyslipidemia and increased risk for cardiovascular events; however, the use ofstatins in HIV-infected people is complicated by pharmacokinetic interactions and overlapping toxicities with antiretroviral medications. Policosanol is a dietary supplement derived from sugar cane that is widely used as a statin alternative in Latin America. PRIMARY STUDY OBJECTIVE: To collect feasibility data on sugar cane-derived policosanol to normalize dyslipidemic profiles in a sample of medically underserved HIV-infected people. METHODS/DESIGN: Randomized, controlled, double-blind clinical trial. SETTING: Two infectious disease outpatient clinics located in a Health Resources Service Administration-designated medically underserved neighborhood in Chicago, Illinois. PARTICIPANTS: Fifty-four clinically stable HIV-infected people (91% black) with at least one lipid abnormality that warranted dietary modifications and/or drug therapy. INTERVENTION: Participants received either 20 mg/day of policosanol or placebo for 12 weeks, followed by a 4-week washout and crossover to the other arm. PRIMARY OUTCOME MEASURES: Efficacy measures included the standard lipid panel (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides) and nuclear magnetic resonance (NMR)-derived lipoprotein particle profiles. Safety measures included CD4+ T lymphocyte counts, plasma HIV ribonucleic acid levels, serum creatinine, and liver function tests. RESULTS: Policosanol supplementation was not associated with normalization of any dyslipidemic parameters as measured by the standard lipid panel or NMR spectroscopy-measured lipoprotein size or concentration. The supplement was well tolerated and was not associated with any changes in parameters of HIV disease progression. CONCLUSIONS: Our findings corroborate recent studies conducted outside Cuba that have failed to find any lipid modulatory effects for policosanol.

Distinct functions of activated protein C differentially attenuate acute kidney injury.

Administration of activated protein C (APC) protects from renal dysfunction, but the underlying mechanism is unknown. APC exerts both antithrombotic and cytoprotective properties, the latter via modulation of protease-activated receptor-1 (PAR-1) signaling. We generated APC variants to study the relative importance of the two functions of APC in a model of LPS-induced renal microvascular dysfunction. Compared with wild-type APC, the K193E variant exhibited impaired anticoagulant activity but retained the ability to mediate PAR-1-dependent signaling. In contrast, the L8W variant retained anticoagulant activity but lost its ability to modulate PAR-1. By administering wild-type APC or these mutants in a rat model of LPS-induced injury, we found that the PAR-1 agonism, but not the anticoagulant function of APC, reversed LPS-induced systemic hypotension. In contrast, both functions of APC played a role in reversing LPS-induced decreases in renal blood flow and volume, although the effects on PAR-1-dependent signaling were more potent. Regarding potential mechanisms for these findings, APC-mediated PAR-1 agonism suppressed LPS-induced increases in the vasoactive peptide adrenomedullin and infiltration of iNOS-positive leukocytes into renal tissue. However, the anticoagulant function of APC was responsible for suppressing LPS-induced stimulation of the proinflammatory mediators ACE-1, IL-6, and IL-18, perhaps accounting for its ability to modulate renal hemodynamics. Both variants reduced active caspase-3 and abrogated LPS-induced renal dysfunction and pathology. We conclude that although PAR-1 agonism is solely responsible for APC-mediated improvement in systemic hemodynamics, both functions of APC play distinct roles in attenuating the response to injury in the kidney.

Electronic Nose Analysis of Exhaled Breath Volatiles to Identify Lung Cancer Cases: A Systematic Review.

The purpose of our review was to analyze evidence of the validity of electronic noses to discriminate persons with lung cancer from healthy control subjects and to advance implications for this technology in the care of people living with HIV. A computerized database search of the literature (published 1946-2018) was conducted to identify studies that used electronic nose-generated smellprints to discriminate persons with lung cancer from healthy control subjects. Fifteen articles met the sampling criteria. In 14 studies, mean sensitivity and specificity values from a single training sample were 84.1% and 80.9%, respectively. Five studies applied the prediction model obtained from the training sample to a separate validation sample; mean sensitivity was 88.2%, and mean specificity was 70.2%. Findings suggest that breath smellprints are valid markers of lung cancer and may be useful screening measures for cancer. No studies included people living with HIV; additional studies are needed to assess generalizability to this population.

Physical Activity and Cognitive Health Among People Living With HIV: An Integrative Review.

The purpose of our review was to analyze evidence related to physical activity (PA) and cognitive health in people living with HIV (PLWH), appraise psychometric characteristics of study measures, and calculate effect sizes. A computerized database search of the literature published between 1996 and 2017 was examined for correlational and observational studies that included a sample of PLWH, measured PA, and measured cognitive health. Seven articles met the sampling criteria. Of which, six studies used a cross-sectional design; one used a longitudinal design. All but one found significant positive associations between PA and cognitive health in PLWH. Four studies showed a moderate to high effect for PA on cognitive function (Cohen's d values = 0.45-0.58). None reported sample-specific reliability and validity estimates for PA and cognitive health instruments. PA is a modifiable factor that may delay the onset of cognitive impairment and decline among PLWH.

Anesthesia Exposure in the Young Child and Long-term Cognition: An Integrated Review.

Millions of children every year undergo seemingly safe general anesthetics for surgical procedures and imaging studies. Anesthetic agents have been shown to cause detrimental effects on brain cell survival and cognitive function in animals. As a result, the safety of general anesthetics in children is an active field of investigation. The objective of this review is to evaluate the human research on anesthesia neurotoxicity in the young child. Three databases were searched for studies on anesthesia exposure in infants and children. Positive clinical outcomes in several studies showed no difference in cognitive function between children exposed and unexposed to anesthesia. Research findings also demonstrated negative clinical outcomes following anesthesia exposure, including physical changes on magenetic resonance imaging such as lower gray matter density in the occipital cortex and cerebellum; lower scores on performance IQ, listening comprehension, and expressive language; overrepresentation in the lowest fifth percentile of academic achievement; and increased risk of learning disabilities. More studies are needed that simultaneously measure cognitive function, physical changes, and disability risk to learn how these factors interact in the human brain.