Place of Death for Young Adults With Chronic Illness.

BACKGROUND: Little is known about where young adults with chronic illness die in the United States and factors associated with place of death. OBJECTIVES: This study aimed to examine place of death and factors associated with place of death for young adults with chronic illness using the most recent national data. METHODS: Our sample ( N = 405,535) from the National Center for Health Statistics Division of Vital Statistics death certificate data (2003-2018) included young adults (age 18-39 years) who died from chronic conditions common in childhood or young adulthood. Conditions were grouped by underlying pathophysiology (oncological, cardiovascular, neuromuscular, metabolic, hematological/immunological, renal, chromosomal/congenital, gastrointestinal, and respiratory). Place of death was dichotomized into acute care (inpatient, outpatient/emergency room, and dead on arrival) or nonacute care (home, hospice, nursing home/long-term care, other, and unknown). Examined factors were gender, year of death, age, race (White, Black, Asian/Pacific Islander, American Indian/Alaskan Native), cause of death, and city of residence population (100,000 or greater and under 100,000). Descriptive statistics and logistic regression were used to examine factors related to place of death. RESULTS: Over half of young adults died in acute care settings. Young adults who were Asian/Pacific Islander or Black or who died from a respiratory or renal cause of death were most likely to die in an acute care setting. Rates of acute care death decreased over the studied years. DISCUSSION: Many young adults died in an acute care setting. Race and cause of death were the most influential factors associated with place of death. Young adults with an oncological cause of death were less likely to die in an acute care setting than patients with other underlying causes. This may indicate that specific care needs or preferences at the end of life may differ in certain disease populations and may affect place of death. Previous research has shown similar results in other developmental populations; however, given the complex psychosocial concerns that often arise during young adulthood, further research is needed to describe how the young adult status may specifically affect place of death.

Families Addressing Cancer Together (FACT): feasibility and acceptability of a web-based psychosocial intervention for parents with cancer.

PURPOSE: Although parents with cancer report that talking with their children about cancer and dying is distressing, accessible support is rare. We assessed the feasibility, acceptability, and preliminary effects of Families Addressing Cancer Together (FACT), a web-based, tailored psychosocial intervention to help parents talk about their cancer with their children. METHODS: This pilot study used a pre-posttest design. Eligible participants were parents with new or metastatic solid tumors who had minor (ages 3-18) children. Participants who completed baseline assessments received online access to FACT. We assessed feasibility through enrollment and retention rates and reasons for study refusal. Acceptability was evaluated by satisfaction ratings. We examined participants' selection of intervention content and preliminary effects on communication self-efficacy and other psychosocial outcomes (depression and anxiety symptoms, health-related quality of life, family functioning) at 2- and 12-week post-intervention. RESULTS: Of 68 parents we approached, 53 (78%) agreed to participate. Forty-six parents completed baseline assessments and received the FACT intervention. Of the 46 participants, 35 (76%) completed 2-week assessments, and 25 (54%) completed 12-week assessments. Parents reported that FACT was helpful (90%), relevant (95%), and easy to understand (100%). Parents' psychosocial outcomes did not significantly improve post-intervention, but parents endorsed less worry about talking with their child (46% vs. 37%) and reductions in the number of communication concerns (3.4 to 1.8). CONCLUSION: The FACT intervention was feasible, acceptable, and has potential to address communication concerns of parents with cancer. A randomized trial is needed to test its efficacy in improving psychological and parenting outcomes. TRIAL REGISTRATION: This study was IRB-approved and registered with clinicaltrials.gov (NCT04342871).

A Study on the Behavior Patterns of Liquid Aerosols Using Disinfectant Chloromethylisothiazolinone/Methylisothiazolinone Solution.

This study evaluates the behavioral characteristics of components (methylisothiazolinone (MIT) and chloromethylisothiazolinone (CMIT)) contained in disinfectant solutions when they convert to liquid aerosols. The analytical method for MIT and CMIT quantitation was established and optimized using sorbent tube/thermal desorber-gas chromatography-mass spectrometry system; their behavioral characteristics are discussed using the quantitative results of these aerosols under different liquid aerosol generation conditions. MIT and CMIT showed different behavioral characteristics depending on the aerosol mass concentration and sampling time (sampling volume). When the disinfectant solution was initially aerosolized, MIT and CMIT were primarily collected on glass filter (MIT = 91.8 ± 10.6% and CMIT = 90.6 ± 5.18%), although when the generation and filter sampling volumes of the aerosols increased to 30 L, the relative proportions collected on the filter decreased (MIT = 79.0 ± 12.0% and CMIT = 39.7 ± 8.35%). Although MIT and CMIT had relatively high vapor pressure, in liquid aerosolized state, they primarily accumulated on the filter and exhibited particulate behavior. Their relative proportions in the aerosol were different from those in disinfectant solution. In the aerosol with mass concentration of ≤5 mg m-3, the relative proportion deviations of MIT and CMIT were large; when the mass concentration of the aerosol increased, their relative proportions constantly converged at a lower level than those in the disinfectant solution. Hence, it can be concluded that the behavioral characteristics and relative proportions need to be considered to perform the quantitative analysis of the liquid aerosols and evaluate various toxic effects using the quantitative data.

Oncological Impact of Lateral Lymph Node Dissection After Preoperative Chemoradiotherapy in Patients with Rectal Cancer.

PURPOSE: To evaluate the efficacy of selective lateral lymph node dissection (LLND) and the effect of preoperative chemoradiotherapy (PCRT) in patients with LLN ≥ 5 mm. METHODS: Patients who underwent PCRT for rectal cancer were classified: (A) total mesorectal excision (TME)-only with LLN < 5 mm (2001-2009, n = 474), (B) TME-only with LLN < 5 mm (2011-2016, n = 273), (C) TME-only with LLN ≥ 5 mm (2001-2009, n = 102), and (D) TME-LLND with LLN ≥ 5 mm (2011-2016, n = 69). Subgroup analysis was performed in patients with LLN ≥ 5 mm based on the reduction in LLN size to < 5 mm or not on restaging MRI after PCRT. RESULTS: Oncological outcomes did not differ between groups A and B. Group D had lower 3-year local recurrence (LR) (20.13% vs 5.39%, P = 0.0013) and higher relapse-free survival (RFS) (65.83% vs 77.11%, P = 0.0436) than group C, while the 3-year overall survival (OS) was not significantly different between the two groups (87.64% vs 93.53%, P = 0.0670). In patients with reduction of LLN size from ≥ 5 mm to < 5 mm, LLND significantly reduced LR than did TME alone, but there were no significant differences in survival outcomes. In patients without reduction of LLN size to < 5 mm, LLND reduced LR and improved RFS compared with TME alone. CONCLUSIONS: Selective LLND reduced LR and improved RFS in patients with LLN ≥ 5 mm. Selective LLND reduced LR in patients with reduction of LLN size from ≥ 5 mm to < 5 mm after PCRT, and improved both LR and RFS in patients without reduction of LLN size to < 5 mm.

Integration of transcriptomics, proteomics and metabolomics identifies biomarkers for pulmonary injury by polyhexamethylene guanidine phosphate (PHMG-p), a humidifier disinfectant, in rats.

Polyhexamethylene guanidine phosphate (PHMG-p) was used as a humidifier disinfectant in Korea. PHMG induced severe pulmonary fibrosis in Koreans. The objective of this study was to elucidate mechanism of pulmonary toxicity caused by PHMG-p in rats using multi-omics analysis. Wistar rats were intratracheally instilled with PHMG-p by single (1.5 mg/kg) administration or 4-week (0.1 mg/kg, 2 times/week) repeated administration. Histopathologic examination was performed with hematoxylin and eosin staining. Alveolar macrophage aggregation and granulomatous inflammation were observed in rats treated with single dose of PHMG-p. Pulmonary fibrosis, chronic inflammation, bronchiol-alveolar fibrosis, and metaplasia of squamous cell were observed in repeated dose group. Next generation sequencing (NGS) was performed for transcriptome profiling after mRNA isolation from bronchiol-alveoli. Bronchiol-alveoli proteomic profiling was performed using an Orbitrap Q-exactive mass spectrometer. Serum and urinary metabolites were determined using 1H-NMR. Among 418 differentially expressed genes (DEGs) and 67 differentially expressed proteins (DEPs), changes of 16 mRNA levels were significantly correlated with changes of their protein levels in both single and repeated dose groups. Remarkable biological processes represented by both DEGs and DEPs were defense response, inflammatory response, response to stress, and immune response. Arginase 1 (Arg1) and lipocalin 2 (Lcn2) were identified to be major regulators for PHMG-p-induced pulmonary toxicity based on merged analysis using DEGs and DEPs. In metabolomics study, 52 metabolites (VIP > 0.5) were determined in serum and urine of single and repeated-dose groups. Glutamate and choline were selected as major metabolites. They were found to be major factors affecting inflammatory response in association with DEGs and DEPs. Arg1 and Lcn2 were suggested to be major gene and protein related to pulmonary damage by PHMG-p while serum or urinary glutamate and choline were endogenous metabolites related to pulmonary damage by PHMG-p.

Effects of pharmacist interventions on reducing prescribing errors of investigational drugs in oncology clinical trials.

OBJECTIVES: This study aimed to investigate the effectiveness of pharmacist intervention in reducing and preventing prescribing errors of investigational drugs for cancer patients. MATERIALS AND METHODS: A retrospective study was conducted during two periods: a baseline period from December 2015 to June 2016 and an intervention period from July 2016 to February 2017. The investigational drug service (IDS) pharmacists performed active interventions during the intervention period. RESULTS: Among 12,387 investigational drug orders, 395 (6.1%) prescribing errors were detected in 6477 orders at the baseline period, and 278 errors (4.7%) were detected in 5,910 orders at the intervention period. To identify factors that affect prescribing errors, three models were constructed for the multivariate analysis. Among factors affecting prescribing errors, sponsor initiated trial (SIT) was the strongest factor (AOR: 4.16, 95% CI: 3.31-5.23). Pharmacist intervention reduced prescribing errors by at least 25% in all constructed models after adjusting for confounding variables. Prescribing errors were 1.3 times higher when dealing with intravenous medications than when dealing with oral medications. There were 60% fewer prescribing errors in the blinded study than in the open study. SIT and multi-center/multi-nation studies had 4.2 and 2.4 times more frequent prescribing errors than in investigator-initiated trials (IIT) and single-center/single-nation studies, respectively. Fewer errors occurred in phase 2 and trials covering both phase 1 and phase 2 (phase 1/2) than in phase 3 trials. CONCLUSIONS: The IDS pharmacist intervention in cancer clinical trials was associated with significant reductions in prescribing errors and may lead to increased medication safety.

Experience with Temporary Centrifugal Pump Bi-ventricular Assist Device for Pediatric Acute Heart Failure: Comparison with ECMO.

Though ventricular assist devices (VADs) are an important treatment option for acute heart failure, an extracorporeal membrane oxygenator (ECMO) is usually used in pediatric patients for several reasons. However, a temporary centrifugal pump-based Bi-VAD might have clinical advantages versus ECMO or implantable VADs. From January 2000 to July 2018, we retrospectively reviewed 36 pediatric patients who required mechanical circulatory support (MCS) for acute heart failure. Cases with postoperative MCS were excluded. Since 2016, we have tried to immediately add a right VAD rather than ECMO, when the patients begin to present features of right heart failure after left VAD support started in cases that the patients' respiratory function did not require an oxygenator. Original diagnoses included dilated cardiomyopathy (n = 18), myocarditis (n = 11), and others (n = 7). Eleven patients were supported by Bi-VAD, and 25 patients were supported by ECMO; of these. Four patients were successfully weaned from VAD, and 10 patients were weaned from ECMO. Eleven patients underwent heart transplantation. Overall, we have 15 (41.7%) early mortalities. There were no significant differences in early mortality, morbidity, and weaning rate between the Bi-VAD group and the ECMO group. During the support, patients with Bi-VADs significantly required fewer platelets and showed less hemolysis than ECMO patients. Patients with myocarditis were successfully weaned from Bi-VAD support and bridged to transplantation thereafter. A temporary centrifugal pump-based Bi-VAD was clinically comparable to ECMO for pediatric patients with acceptable pulmonary function.

Use of Palliative Care Consultation Services for Infants With Life-Threatening Conditions in a Metropolitan Hospital.

BACKGROUND: Palliative care is becoming an important component for infants with life-limiting or life-threatening conditions and their families. Yet palliative care practices appear to be inconsistent and sporadically used for infants. PURPOSE: The purpose of this study was to describe the use of an established pediatric palliative care team for seriously ill infants in a metropolitan hospital. METHODS: This was a retrospective medical record review. FINDINGS: The population included 64 infants who were admitted to a level IV neonatal intensive care unit (NICU) and then died during hospitalization between January 2015 and December 2016. Most infants died in an ICU (n = 63, 95%), and only 20 infants (31%) received palliative care consultation. Most common reasons for consultation were care coordination, defining goals of care and end-of-life planning, and symptom management. IMPLICATIONS FOR PRACTICE: Palliative care consultation at this institution did not change the course of end-of-life care. Interventions provided by the ICU team to infants surrounding end of life were similar to those in infants receiving palliative care services from the specialists. Our findings may be useful for developing guidelines regarding how to best utilize palliative care services for infants with life-threatening conditions who are admitted to an ICU. IMPLICATIONS FOR RESEARCH: These finding support continued research in neonatal palliative care, more specifically the impact of palliative care guidelines and algorithms.

Kathon Induces Fibrotic Inflammation in Lungs: The First Animal Study Revealing a Causal Relationship between Humidifier Disinfectant Exposure and Eosinophil and Th2-Mediated Fibrosis Induction.

Currently available toxicity data on humidifier disinfectants are primarily limited to polyhexamethylene guanidine phosphate-induced lung fibrosis. We, therefore, investigated whether the sterilizer component Kathon, which is a mixture of chloromethylisothiazolinone and methylisothiazolinone, induces fibrotic lung injury following direct lung exposure in an animal model. Mice were intratracheally instilled with either the vehicle or Kathon. Differential cell counts, cytokine analysis, and histological analysis of lung tissue were then performed to characterize the injury features, and we investigated whether Kathon altered fibrosis-related gene expression in lung tissues via RNA-Seq and bioinformatics. Cell counting showed that Kathon exposure increased the proportion of macrophages, eosinophils, and neutrophils. Moreover, T helper 2 (Th2) cytokine levels in the bronchoalveolar lavage were significantly increased in the Kathon groups. Histopathological analysis revealed increased perivascular/alveolar inflammation, eosinophilic cells, mucous cell hyperplasia, and pulmonary fibrosis following Kathon exposure. Additionally, Kathon exposure modulated the expression of genes related to fibrotic inflammation, including the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, extracellular signal regulated kinase (ERK)1 and ERK2 cascade, extracellular matrix (ECM)-receptor interaction pathway, transforming growth factor beta receptor signaling pathway, cellular response to tumor necrosis factor, and collagen fibril organization. Our results suggest that Kathon exposure is associated with fibrotic lung injury via a Th2-dependent pathway and is thus a possible risk factor for fibrosis.

Diesel Exhaust Particulates Induce Neutrophilic Lung Inflammation by Modulating Endoplasmic Reticulum Stress-Mediated CXCL1/KC Expression in Alveolar Macrophages.

Diesel exhaust particulates (DEP) have adverse effects on the respiratory system. Endoplasmic reticulum (ER) abnormalities contribute to lung inflammation. However, the relationship between DEP exposure and ER stress in the respiratory immune system and especially the alveolar macrophages (AM) is poorly understood. Here, we examined ER stress and inflammatory responses using both in vivo and in vitro study. For in vivo study, mice were intratracheally instilled with 25, 50, and 100 µg DEP and in vitro AM were stimulated with DEP at 1, 2, and 3 mg/mL. DEP increased lung weight and the number of inflammatory cells, especially neutrophils, and inflammatory cytokines in bronchoalveolar lavage fluid of mice. DEP also increased the number of DEP-pigmented AM and ER stress markers including bound immunoglobulin protein (BiP) and CCAAT/enhancer binding protein-homologous protein (CHOP) were upregulated in the lungs of DEP-treated mice. In an in vitro study, DEP caused cell damage, increased intracellular reactive oxygen species, and upregulated inflammatory genes and ER stress-related BiP, CHOP, splicing X-box binding protein 1, and activating transcription factor 4 expressions in AM. Furthermore, DEP released the C-X-C Motif Chemokine Ligand 1 (CXCL1/KC) in AM. In conclusion, DEP may contribute to neutrophilic lung inflammation pathogenesis by modulating ER stress-mediated CXCL1/KC expression in AM.

Patient and caregiver outcomes at the integrated memory care clinic.

The purpose of this longitudinal cohort study was to explore the outcomes of persons living with dementia (PLWD) and their caregivers during their first 9 months at the Integrated Memory Care Clinic (IMCC). IMCC advanced practice registered nurses provide dementia care and primary care simultaneously and continuously to PLWD until institutionalization. Changes were examined in caregivers' psychological well-being (perceived stress, depressive symptoms, caregiver burden, and anxiety) and health status and in PLWDs' quality of life and neuropsychiatric symptoms. Data were collected at baseline, then 3 and 6 months post-baseline. Forty-two caregivers completed all 3 assessments. Most variables remained unchanged. Statistically significant improvements in 5 sub-scales of the Neuropsychiatric Inventory were observed: caregivers' distress regarding their PLWDs' delusions and anxiety, and PLWDs' severity of delusions, depression, and total symptom severity. Further testing of the IMCC is required, including in quasi-experimental studies, to determine its efficacy.

Local recurrence of brain metastasis reduced by intra-operative hyperthermia treatment.

PURPOSE: Brain metastasis is a common complication in cancer patients. Local recurrence after total resection of metastatic brain tumor has been frequently reported. In this study, we developed a new hyperthermia device and applied it to metastatic brain tumor patients intra-operatively to study if hyperthermia treatment could reduce local tumor recurrence. MATERIALS AND METHODS: A total of 63 metastatic brain patients were enrolled in the study with an informed consent obtained from every patient. After total resection of the tumor, the hyperthermia device was applied intra-operatively to the resection cavity. The surrounding brain tissue at 5 mm in depth from the tumor resection margin was raised to 42.5 °C for a total of 60 minutes (Clinical Research Information Service Registration Number: KCT0001308). RESULTS: A total of 10 local recurrences were observed in 63 patients who received hyperthermia treatment showing a local recurrence rate of 15.8%. It was significantly lower than the local recurrence rate of those who received conventional treatment (34%) when analyzed with one tailed z-test (p value: .001). Kaplan-Meier analysis also showed a significantly lower recurrence rate in the hyperthermia treatment group (p value: .0003). Complications included two cases of seizures and two cases of wound infection. CONCLUSIONS: Results of this study suggest that intra-operative hyperthermia treatment after total resection of metastatic brain tumor could reduce local recurrence of tumor. We believe that intra-operative hyperthermia treatment could be used as an adjuvant therapy to surgery and post-operative radiotherapy, or as a salvage treatment in patients who cannot receive further radiotherapy.

Time-course transcriptomic alterations reflect the pathophysiology of polyhexamethylene guanidine phosphate-induced lung injury in rats.

Objective: Humidifier-disinfectant-induced lung injury is a new syndrome associated with a high mortality rate and characterized by severe hypersensitivity pneumonitis, acute interstitial pneumonia, or acute respiratory distress syndrome. Polyhexamethylene guanidine phosphate (PHMG-P), a guanidine-based antimicrobial agent, is a major component associated with severe lung injury. In-depth studies are needed to determine how PHMG-P affects pathogenesis at the molecular level. Therefore, in this study, we analyzed short-term (4 weeks) and long-term (10 weeks) PHMG-P-exposure-specific gene-expression patterns in rats to improve our understanding of time-dependent changes in fibrosis.Materials and methods: Gene-expression profiles were analyzed in rat lung tissues using DNA microarrays and bioinformatics tools.Results: Clustering analysis of gene-expression data showed different gene-alteration patterns in the short- and long-term exposure groups and higher sensitivity to gene-expression changes in the long-term exposure group than in the short-term exposure group. Supervised analysis revealed 34 short-term and 335 long-term exposure-specific genes, and functional analysis revealed that short-term exposure-specific genes were involved in PHMG-P-induced initial inflammatory responses, whereas long-term exposure-specific genes were involved in PHMG-P-related induction of chronic lung fibrosis.Conclusion: The results of transcriptomic analysis were consistent with lung histopathology results. These findings indicated that exposure-time-specific changes in gene expression closely reflected time-dependent pathological changes in PHMG-P-induced lung injury.

Comparison of asthma phenotypes in OVA-induced mice challenged via inhaled and intranasal routes.

BACKGROUND: The respiratory system is exposed to various allergens via inhaled and intranasal routes. Murine models of allergic lung disease have been developed to clarify the mechanisms underlying inflammatory responses and evaluate the efficacy of novel therapeutics. However, there have been no comparative studies on differences in allergic phenotypes following inhaled vs. intranasal allergen challenge. In this study, we compared the asthmatic features of mice challenged via different routes following allergen sensitization and investigated the underlying mechanisms. METHODS: To establish ovalbumin (OVA)-induced allergic asthma models, BALB/c mice were sensitized to 20 µg OVA with 1 mg aluminum hydroxide by the intraperitoneal route and then challenged by inhalation or intranasal administration with 5% OVA for 3 consecutive days. Cellular changes and immunoglobulin (Ig) E levels in bronchoalveolar lavage fluid (BALF) and serum, respectively, were assessed. Histological changes in the lungs were examined by hematoxylin and eosin (H&E) and periodic acid Schiff (PAS) staining. Levels of T helper (Th)2 cytokines including interleukin (IL)-4, -5, and -13 in BALF and epithelial cytokines including IL-25 and -33 in BALF and lung tissues were measured by enzyme-linked immunosorbent assay and western blotting. Airway hyperresponsiveness (AHR) was evaluated by assessing airway resistance (Rrs) and elastance (E) via an invasive method. RESULTS: OVA-sensitized and challenged mice showed typical asthma features such as airway inflammation, elevated IgE level, and AHR regardless of the challenge route. However, H&E staining showed that inflammation of pulmonary vessels, alveolar ducts, and alveoli were enhanced by inhaled as compared to intranasal OVA challenge. PAS staining showed that intranasal OVA challenge induced severe mucus production accompanied by inflammation in bronchial regions. In addition, Th2 cytokine levels in BALF and AHR in lung were increased to a greater extent by inhalation than by intranasal administration of OVA. Epithelial cytokine expression, especially IL-25, was increased in the lungs of mice in the inhaled OVA challenge group. CONCLUSION: OVA-sensitized mice exhibit different pathophysiological patterns of asthma including expression of epithelial cell-derived cytokines depending on the OVA challenge route. Thus, some heterogeneous phenotypes of human asthma can be replicated by varying the mode of delivery after OVA sensitization.

Nurses' roles and challenges in providing end-of-life care in neonatal intensive care units in South Korea.

BACKGROUND: Neonatal Intensive Care Unit (NICU) nurses in Korea often experience challenges in providing care for dying infants and their families. However, there is limited understanding about what contributes to the challenges related to end-of-life care. PURPOSE: To describe NICU nurses' perceived roles and challenges faced while providing end-of-life care in South Korea. METHODS: A qualitative descriptive study was conducted with 20 NICU nurses in South Korea using semi-structured interviews. Participants were recruited from two NICUs in Seoul, where infant mortality is the highest in South Korea. Transcribed interviews were coded by two research personnel, and subsequently, a developed coding book was translated by three research personnel. The codes developed were categorized and peer-reviewed to develop themes using conventional content analysis. RESULTS: Nurses' roles during end-of-life care were grouped into four categories: providing information and support, enhancing attachment between the parents and infants, providing direct care to the infant, and completing documentation. Nurses' perceived challenges during end-of-life care included providing end-of-life care without adequate experience and knowledge, environmental constraints on end-of-life care, and conflicted situations during end-of-life care. CONCLUSION: Although the nurses provided the best care they could, their end-of-life care practice was hindered for various reasons. To enhance NICU nurses' ability to provide and make them more capable of providing high quality EOL care, hospitals need to support nurse education and improve staffing level, and create in NICUs an environment that is favorable for providing EOL care.

Understanding health-related quality of life in adult women with metastatic cancer who have dependent children.

BACKGROUND: Cancer is a leading cause of death among women of parenting age in the United States. Women living with advanced or incurable cancer who have dependent children experience high rates of depression and anxiety as well as unique parenting challenges. To the authors' knowledge, few studies to date have examined the parenting factors associated with health-related quality of life (HRQOL) in women with advanced cancer. METHODS: The authors conducted a cross-sectional, Web-based survey of the psychosocial concerns of 224 women with a tumor-node-metastasis staging system of the AJCC stage IV solid tumor malignancy who had at least 1 child aged <18 years. Participants completed validated measures of HRQOL (Functional Assessment of Cancer Therapy-General [FACT-G]); depression and anxiety symptom severity; functional status; parenting concerns; and investigator-designed questions to assess demographic, communication, and parenting characteristics. Multiple linear regression models were estimated to identify factors associated with FACT-G total and subscale scores. RESULTS: The mean FACT-G score was 66 (standard deviation, 16). The mean Emotional Well-Being subscale scores were particularly low (13; standard deviation, 5). In multivariable linear regression models, parenting variables explained nearly 40% of the HRQOL model variance. In the fully adjusted model, parenting concerns and the absence of parental prognostic communication with children both were found to be significantly associated with HRQOL scores. For each 1-point increase in parenting concern severity, FACT-G scores decreased by 4 points (P = .003). CONCLUSIONS: Women with metastatic cancer who are parents of dependent children are at risk of high psychological distress and low HRQOL. Parenting factors may have a negative influence on HRQOL in this patient population. Cancer 2018;124:2629-36. © 2018 American Cancer Society.

Use of adjuvant chemotherapy in hormone receptor-positive breast cancer patients with or without the 21-gene expression assay.

PURPOSE: We assessed the use of chemotherapy in breast cancer patients to investigate the factors that changed trends in chemotherapy following the adoption of the 21-gene expression assay in tumor genomic profiling. METHODS: Our study used 2033 patients from the National Cancer Center in Korea diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (tumor size of 0.5 cm or larger and 0-3 node metastases) from 2010 to 2015. We analyzed use of the 21-gene expression assay, changes in frequency of adjuvant chemotherapy use, and clinicopathological factors related to adjuvant chemotherapy to assess the impact of the 21-gene expression assay. RESULTS: Adjuvant chemotherapy use declined from 33.33% (2011) to 13.59% (2015) [relative risk (RR), 0.71; 95% CI 0.56-0.89; ptrend = 0.004] in patients with 21-gene expression assay data. Among patients without assay data, adjuvant chemotherapy use decreased from 76.79 to 40.17% between 2010 and 2015 (RR 0.87; 95% CI 0.84-0.91; ptrend < 0.001), especially for patients with node-negative/micrometastasis (RR 0.85; 95% CI 0.81-0.89; ptrend < 0.001). The frequency of adjuvant chemotherapy was significantly decreased after introduction of the 21-gene expression assay (p < 0.001). Tumor size (p < 0.001), progesterone receptor (PgR) status (p = 0.001), and proliferation index (Ki-67) levels (p < 0.001) were important factors for chemotherapy decision-making in node-negative/micrometastasis patients who did not undergo the assay. CONCLUSIONS: For HR-positive, HER2-negative breast cancer patients with 0-1 node metastases, chemotherapy use declined significantly after the adoption of the 21-gene assay. PgR status and Ki-67 were useful for chemotherapy decision-making in cases without the 21-gene assay.

One-Year Linear Trajectories of Symptoms, Physical Functioning, Cognitive Functioning, Emotional Well-being, and Spiritual Well-being Among Patients Receiving Dialysis.

BACKGROUND: This study evaluated 1-year linear trajectories of patient-reported dimensions of quality of life among patients receiving dialysis. STUDY DESIGN: Longitudinal observational study. SETTING & PARTICIPANTS: 227 patients recruited from 12 dialysis centers. FACTORS: Sociodemographic and clinical characteristics. MEASUREMENTS/OUTCOMES: Participants completed an hour-long interview monthly for 12 months. Each interview included patient-reported outcome measures of overall symptoms (Edmonton Symptom Assessment System), physical functioning (Activities of Daily Living/Instrumental Activities of Daily Living), cognitive functioning (Patient's Assessment of Own Functioning Inventory), emotional well-being (Center for Epidemiologic Studies Depression Scale, State Anxiety Inventory, and Positive and Negative Affect Schedule), and spiritual well-being (Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale). For each dimension, linear and generalized linear mixed-effects models were used. Linear trajectories of the 5 dimensions were jointly modeled as a multivariate outcome over time. RESULTS: Although dimension scores fluctuated greatly from month to month, overall symptoms, cognitive functioning, emotional well-being, and spiritual well-being improved over time. Older compared with younger participants reported higher scores across all dimensions (all P<0.05). Higher comorbidity scores were associated with worse scores in most dimensions (all P<0.01). Nonwhite participants reported better spiritual well-being compared with their white counterparts (P<0.01). Clustering analysis of dimension scores revealed 2 distinctive clusters. Cluster 1 was characterized by better scores than those of cluster 2 in nearly all dimensions at baseline and by gradual improvement over time. LIMITATIONS: Study was conducted in a single region of the United States and included mostly patients with high levels of function across the dimensions of quality of life studied. CONCLUSIONS: Multidimensional patient-reported quality of life varies widely from month to month regardless of whether overall trajectories improve or worsen over time. Additional research is needed to identify the best approaches to incorporate patient-reported outcome measures into dialysis care.

Application of Computer-Aided Diagnosis on Breast Ultrasonography: Evaluation of Diagnostic Performances and Agreement of Radiologists According to Different Levels of Experience.

OBJECTIVES: To investigate the feasibility of a computer-aided diagnosis (CAD) system (S-Detect; Samsung Medison, Co, Ltd, Seoul, Korea) for breast ultrasonography (US), according to radiologists with various degrees of experience in breast imaging. METHODS: From December 2015 to March 2016, 119 breast masses in 116 women were included. Ultrasonographic images of the breast masses were retrospectively reviewed and analyzed by 2 radiologists specializing in breast imaging (7 and 1 years of experience, respectively) and S-Detect, according to the individual ultrasonographic descriptors from the fifth edition of the American College of Radiology Breast Imaging Reporting and Data System and final assessment categories. Diagnostic performance and the interobserver agreement among the radiologists and S-Detect was calculated and compared. RESULTS: Among the 119 breast masses, 54 (45.4%) were malignant, and 65 (54.6%) were benign. Compared to the radiologists, S-Detect had higher specificity (90.8% compared to 49.2% and 55.4%) and positive predictive value (PPV; 86.7% compared to 60.7% and 63.8%) (all P < .001). Both radiologists had significantly improved specificity, PPV, and accuracy when using S-Detect compared to US alone (all P < .001). The area under the receiving operating characteristic curves of the both radiologists did not show a significant improvement when applying S-Detect compared to US alone (all P > .05). Moderate agreement was seen in final assessments made by each radiologist and S-Detect (κ = 0.40 and 0.45, respectively). CONCLUSIONS: S-Detect is a clinically feasible diagnostic tool that can be used to improve the specificity, PPV, and accuracy of breast US, with a moderate degree of agreement in final assessments, regardless of the experience of the radiologist.

Effect of particulate matter 2.5 on gene expression profile and cell signaling in JEG-3 human placenta cells.

Particulate matter the environmental toxicant, with a diameter less than or equal to 2.5 µm (PM2.5 ) is a common cause of several respiratory diseases. In recent years, several studies have suggested that PM2.5 can influence diverse diseases, such as respiratory diseases, cardiovascular diseases, metabolic diseases, dementia, and female reproductive disorders, and unhealthy birth outcomes. In addition, several epidemiological studies have reported that adverse health effects of PM2.5 can differ depending on regional variations. In the present study, to evaluate specific adverse health effects of PM2.5 , we collected two different PM2.5 samples from an underground parking lot and ambient air, and we evaluated cytotoxicity with eight different cell lines originating from human organs. Then, we selected JEG-3 human placenta cells, which show high cytotoxicity to both PM samples. Through RNA sequencing, gene expression profiling, and a gene ontology (GO) analysis of JEG-3 after exposure to two different PM2.5 samples, we identified 1021 commonly expressed genes involved in immune responses, the regulation of apoptosis, and so forth, which are known to induce several adverse health effects. In addition, we identified genes related to the calcium-signaling pathway, steroid hormone biosynthesis, and the cytokine-cytokine receptor interaction through a Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, we confirmed these gene expressions using qRT-PCR, and the protein levels of mitogen-activated protein kinases and COX-2 with progesterone decreased using western blotting and enzyme-linked immunosorbent assay. In conclusion, this study suggests the possible toxic mechanism of human placenta that might be associated with PM2.5 -induced female reproductive disorders.