Improving the accuracy of noninvasive prenatal testing through size-selection between fetal and maternal cfDNA.

OBJECTIVES: In general, fetal cfDNA is shorter than maternal cfDNA, and accuracy of noninvasive prenatal testing (NIPT) results can be improved by selecting shorter cfDNA fragments to enrich fetal-derived cfDNA. This study investigated potential improvements in the accuracy of NIPT by performing classification and analysis based on differences in cfDNA size. METHODS: We performed paired-end sequencing to identify size ranges of fetal and maternal cfDNA from 62,374 pregnant women. We then developed a size-selection method to isolate and analyze both fetal and maternal cfDNA, defining fetal-derived cfDNA as less than 150 bp and maternal-derived cfDNA as greater than 180 bp. RESULTS: By implementing size-selection method, the accuracy of NIPT was improved, resulting in an increase in the overall positive predictive value for all aneuploidies from 89.57% to 97.1%. This was achieved by enriching both fetal and maternal-derived cfDNA, which increased fetal DNA fraction while the number of false positives for all aneuploidies was reduced by more than 70%. CONCLUSIONS: We identified the differences in read length between fetal and maternal-derived cfDNA, and selectively enriched both shorter and longer cfDNA fragments for subsequent analysis. Our approach can increase the detection accuracy of NIPT for detecting fetal aneuploidies and reduce the number of false positives caused by maternal chromosomal abnormalities.

Effects of nonpharmacological interventions on sleep improvement and delirium prevention in critically ill patients: A systematic review and meta-analysis.

OBJECTIVE: Sleep disturbance and delirium are common problems experienced by critically ill patients in the intensive care unit (ICU). These interrelated issues increase the length of stay in the ICU but might also negatively affect long-term health outcomes. The objective of this study was to identify the nonpharmacological interventions provided to improve sleep or prevent delirium in ICU patients or both and integrate their effect sizes. REVIEW METHODS: This study was a registered systematic review and meta-analysis. We searched MEDLINE, CINAHL, EMBASE, Web of Science, and Cochrane Library from their inception until December 2021. We included randomised controlled trials and nonrandomised controlled trials-(RCT) that provided nonpharmacological interventions and reported sleep or delirium as outcome variables. Studies not published in English or whose full text was not available were excluded. The quality of the evidence was assessed with version 2 of the Cochrane risk-of-bias tool for RCTs and the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I). RESULTS: The systematic review included 118 studies, and the meta-analysis included 100 studies. Overall nonpharmacological interventions had significant effects on subjective sleep quality (standardised mean difference = 0.30, 95% confidence interval [CI] = 0.05 to 0.56), delirium incidence (odds ratio = 0.62, 95% CI = 0.53 to 0.73), and delirium duration (standardised mean difference = -0.68, 95% CI = -0.93 to -0.43). In individual interventions, aromatherapy, music, and massage effectively improved sleep. Exercise, family participation, information giving, cognitive stimulation, bright light therapy, architectural intervention, and bundles/protocols effectively reduced delirium. Light/noise blocking was the only intervention that ensured both sleep improvement and delirium prevention. CONCLUSIONS: Our results suggest nonpharmacological interventions improve sleep and prevent delirium in ICU patients. We recommend that ICU nurses use nonpharmacological interventions that promote person-environment compatibility in their clinical practice. The results of our review can guide nurses in adopting interventions related to sleep and delirium. PROSPERO REFERENCE NUMBER: CRD42021230815.

Enhancing Lung Cancer Classification through Integration of Liquid Biopsy Multi-Omics Data with Machine Learning Techniques.

Early detection of lung cancer is crucial for patient survival and treatment. Recent advancements in next-generation sequencing (NGS) analysis enable cell-free DNA (cfDNA) liquid biopsy to detect changes, like chromosomal rearrangements, somatic mutations, and copy number variations (CNVs), in cancer. Machine learning (ML) analysis using cancer markers is a highly promising tool for identifying patterns and anomalies in cancers, making the development of ML-based analysis methods essential. We collected blood samples from 92 lung cancer patients and 80 healthy individuals to analyze the distinction between them. The detection of lung cancer markers Cyfra21 and carcinoembryonic antigen (CEA) in blood revealed significant differences between patients and controls. We performed machine learning analysis to obtain AUC values via Adaptive Boosting (AdaBoost), Multi-Layer Perceptron (MLP), and Logistic Regression (LR) using cancer markers, cfDNA concentrations, and CNV screening. Furthermore, combining the analysis of all multi-omics data for ML showed higher AUC values compared with analyzing each element separately, suggesting the potential for a highly accurate diagnosis of cancer. Overall, our results from ML analysis using multi-omics data obtained from blood demonstrate a remarkable ability of the model to distinguish between lung cancer and healthy individuals, highlighting the potential for a diagnostic model against lung cancer.

Advances in methylation analysis of liquid biopsy in early cancer detection of colorectal and lung cancer.

Methylation patterns in cell-free DNA (cfDNA) have emerged as a promising genomic feature for detecting the presence of cancer and determining its origin. The purpose of this study was to evaluate the diagnostic performance of methylation-sensitive restriction enzyme digestion followed by sequencing (MRE-Seq) using cfDNA, and to investigate the cancer signal origin (CSO) of the cancer using a deep neural network (DNN) analyses for liquid biopsy of colorectal and lung cancer. We developed a selective MRE-Seq method with DNN learning-based prediction model using demethylated-sequence-depth patterns from 63,266 CpG sites using SacII enzyme digestion. A total of 191 patients with stage I-IV cancers (95 lung cancers and 96 colorectal cancers) and 126 noncancer participants were enrolled in this study. Our study showed an area under the receiver operating characteristic curve (AUC) of 0.978 with a sensitivity of 78.1% for colorectal cancer, and an AUC of 0.956 with a sensitivity of 66.3% for lung cancer, both at a specificity of 99.2%. For colorectal cancer, sensitivities for stages I-IV ranged from 76.2 to 83.3% while for lung cancer, sensitivities for stages I-IV ranged from 44.4 to 78.9%, both again at a specificity of 99.2%. The CSO model's true-positive rates were 94.4% and 89.9% for colorectal and lung cancers, respectively. The MRE-Seq was found to be a useful method for detecting global hypomethylation patterns in liquid biopsy samples and accurately diagnosing colorectal and lung cancers, as well as determining CSO of the cancer using DNN analysis.Trial registration: This trial was registered at ClinicalTrials.gov (registration number: NCT04253509) for lung cancer on 5 February 2020, https://clinicaltrials.gov/ct2/show/NCT04253509 . Colorectal cancer samples were retrospectively registered at CRIS (Clinical Research Information Service, registration number: KCT0008037) on 23 December 2022, https://cris.nih.go.kr , https://who.init/ictrp . Healthy control samples were retrospectively registered.

Health-related quality of life measured with the EQ-5D-5L in critical care survivors: A cross-sectional study.

OBJECTIVES: The aim of this study was to investigate health-related quality of life (HRQOL) and related factors in intensive care unit survivors one-12 months after discharge. RESEARCH METHODOLOGY/DESIGN: This cross-sectional survey included survivors who had been admitted to an intensive care unit for ≥48 hours. MAIN OUTCOME MEASURES: HRQOL was measured using the EQ-5D-5L profile, which evaluates five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) on five levels (no, slight, moderate, severe, and extreme problems), EQ-VAS (score range 0-100, 100 indicating best health) and EQ values (score range -0.066-1, 1 indicating best health). The factors influencing HRQOL were analyzed by Tobit regression. SETTING: Survivors treated in an intensive care unit at six institutions in Korea. RESULTS: Only 7.9% of the 534 participants had self-reported profiles of no health problems in all five dimensions. The proportion of participants with slight problems was highest in pain/discomfort with 85.0%. The proportion with severe problems was highest in usual activities with 21.7%, followed by mobility with 21.0%. The median and interquartile range of the EQ-VAS and EQ values were 60.00 (45.00 to 75.00) and 0.72 (0.52 to 0.80), respectively. Negative impact factors on HRQOL included older age, women, residing in a long term care facility, unemployment, emergency intensive care admission, and intensive care stay ≥ 7 days. CONCLUSION: HRQOL among Korean intensive care survivors is low. The level of problems in physical dimensions is more severe than that in mental health dimensions. Early rehabilitation in the intensive care unit should be provided to facilitate long-term recovery.

Post-intensive care unit depression among critical care survivors: A nationwide population-based study.

AIM: To investigate the incidence of post-intensive care unit (ICU) depression and its risk factors among critical care survivors. METHODS: The study data were extracted from the database of the National Health Insurance Service of Korea. We retrospectively analyzed data from 161,977 adult patients who were admitted to the ICU for more than 24 hr from January 1, 2012 to December 31, 2014 and survived for more than 1 year after discharge. Risk factors for newly diagnosed depression (Code F32) were analyzed using multiple logistic regression analysis. RESULTS: The incidence of post-ICU depression was 18.5%. The major risk factors were enteral nutrition (odds ratio [OR] = 2.28, 95% confidence interval [CI] = 2.19-2.36), cerebrovascular disease (OR = 1.59, 95% CI = 1.54-1.64), and hemi/paraplegia (OR = 1.48, 95% CI = 1.41-1.56). It was observed that cardiopulmonary resuscitation (OR = 0.55, 95% CI = 0.50-0.61) and myocardial infarction (OR = 0.75, 95% CI = 0.71-0.79) lowered depression. CONCLUSIONS: The incidence of post-ICU depression was high and influenced by ICU treatment and physical impairments. Healthcare providers must pay attention to the psychological changes in survivors with major risk factors in the recovery process.

Influencing Factors and Consequences of Workplace Bullying among Nurses: A Structural Equation Modeling.

PURPOSE: The purpose of this study was to build and test a model outlining the factors related to workplace bullying among nurses. The hypothesized model included authentic leadership and a relationship-oriented organizational culture as influencing factors, symptom experience and turnover intention as consequences, and positive psychological capital as a mediator of workplace bullying among nurses. METHODS: We obtained structured questionnaire data from 301 nurses working at hospitals in South Korea. Based on these data, the developed model was verified via a structural equation modeling analysis using SPSS and AMOS program. RESULTS: The fit indices of the hypothesized model satisfied recommended levels; χ2 = 397.58 (p < .001), normed χ2 (χ2/df) = 1.82, RMR = .05, TLI = .93, CFI = .94, RMSEA = .05. A relationship-oriented organizational culture had a direct effect on workplace bullying (ß = -.48, p < .001). Furthermore, workplace bullying had a direct effect on symptom experience (ß = .36, p < .001), and this relationship was mediated by positive psychological capital (ß = .15, p = .003). Workplace bullying also had an indirect effect on turnover intention (ß = .20, p = .007). Finally, symptom experience had a direct effect on turnover intention (ß = .31, p = .002). CONCLUSION: These results suggest that workplace bullying among nurses may be prevented by constructing a relationship-oriented organizational culture, as long as employees have sufficient positive psychological capital. In this regard, workplace bullying among nurses should be addressed using a comprehensive strategy that considers both individual and organizational factors.

Effect of nonpharmacological interventions for the prevention of delirium in the intensive care unit: A systematic review and meta-analysis.

PURPOSE: We aimed to classify nonpharmacological interventions used for preventing delirium in the intensive care unit (ICU), and estimate their effect size. MATERIALS AND METHODS: In this systematic review and meta-analysis, the literature was searched and studies were selected based on the PRISMA flow chart. Data sources included MEDLINE, Cochrane, CINHAHL, PsyInfo, and EMBASE. We used Cochrane's Effective Practice and Organisation of Care (EPOC) criteria in study design and quality assessment of the meta-analysis. RESULTS: This systematic review and meta-analysis included 35 and 15 studies, respectively. Studies were grouped into nine intervention types: multicomponent (16 studies), physical environment (9), daily interruption of sedation (2), exercise (2), patient education (2), automatic warning system (1), cerebral hemodynamics improving (1), family participation (1), and sedation reducing protocol (1). The effect size of preventive nonpharmacological interventions had an odds ratio (OR) of 0.66 (95% confidence interval [CI], 0.50-0.86) for delirium occurrence, and an OR of 0.31 (95% CI, 0.10-0.94) for delirium duration. Although relevant studies by interventions were lacking, a partial subgroup analysis by intervention was performed. CONCLUSIONS: Nonpharmacological interventions were effective in reducing the duration and occurrence of delirium. Consistent application and development of nonpharmacological interventions for use in the ICU are important.

[Development and Validation of a Measurement to Assess Person-centered Critical Care Nursing].

PURPOSE: The purpose of this study was to develop a scale to measure person-centered critical care nursing and verify its reliability and validity. METHODS: A total of 38 preliminary items on person-centered critical care nursing were selected using content validity analysis of and expert opinion on 72 candidate items derived through literature review and qualitative interviews. We conducted a questionnaire survey with 477 nurses who worked in intensive care units. The collected data were analyzed using exploratory factor analysis (EFA) and confirmative factor analysis (CFA) with SPSS and AMOS 24.0 program. RESULTS: EFA was performed with principal axis factor analysis and Varimax rotation. The 15 items in 4 factors that accounted for 50.8% of the total variance were identified by deleting the items that were not meet the condition that the commonality should be .30 or more and the factor loading over .40. We named the factors as compassion, individuality, respect, and comfort, respectively. The correlation coefficient between this scale and the Caring Perception Scale was r=.57 (p<.001), which determined concurrent validity. The item-total correlation values ranged from .39 to .63, and the internal consistency for the scale was Cronbach's α=.84. CONCLUSION: The reliability and validity of the 15 item person-centered critical care nursing scale were verified. It is expected that the use of this scale would expand person-centered care in critical care nursing.

Effects of a Cognitive Rehearsal Program on Interpersonal Relationships, Workplace Bullying, Symptom Experience, and Turnover Intention among Nurses: A Randomized Controlled Trial.

PURPOSE: This research aimed to investigate the effects of a cognitive rehearsal program (CRP) on workplace bullying among nurses. METHODS: A randomized controlled trial was performed. Participants were 40 nurses working in different university hospitals in B city, South Korea. The experimental group was provided with a 20-hour CRP comprising scenarios on bullying situations, standard communication, and role-playing. To evaluate effects of the CRP, we measured interpersonal relationships, workplace bullying, symptom experience, and turnover intention at preand post-intervention. Follow-up effect was measured in the experimental group only at 4 weeks after the intervention. RESULTS: After the intervention, there were significant differences in interpersonal relationships (F=6.21, p=.022) and turnover intention (F=5.55, p=.024) between experimental and wait-list groups. However, there was no significant difference in workplace bullying or symptom experience between the 2 groups. The beneficial effects on interpersonal relationships and turnover intention lasted at least up to 4 weeks after CRP. CONCLUSION: The CRP for workplace bullying improves interpersonal relationships and decreases turnover intention. So it can be utilized as one of the personal coping strategies to reduce the the turnover among nurses. Further studies on the effects of unit- or hospital-based CRP and on the long-term effects of CRP are necessary.

[A Grounded Theory Approach on Nurses' Experience with Workplace Bullying].

PURPOSE: The purpose of this qualitative study was to explore the workplace bullying experience of Korean nurses. METHODS: Participants were twenty current or former hospital nurses who had experienced workplace bullying. Data were collected through focus group and individual in-depth interviews from February to May, 2015. Theoretical sampling method was applied to the point of theoretical saturation. Transcribed interview contents were analyzed using Corbin and Strauss's grounded theory method. RESULTS: A total of 110 concepts, 48 sub-categories, and 17 categories were identified through the open coding process. As a result of axial coding based on the paradigm model, the central phenomenon of nurses' workplace bullying experience was revealed as 'teaching that has become bullying', and the core category was extracted as 'surviving in love-hate teaching' consisting of a four-step process: confronting reality, trial and error, relationship formation, and settlement. The relationship formation was considered to be the key phase to proceed to the positive settlement phase, and the participants utilized various strategies such as having an open mind, developing human relationships, understanding each other in this phase. CONCLUSION: The in-depth understanding of the workplace bullying experience has highlighted the importance of effective communication for cultivating desirable human relationships between nurses.