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    Mechanisms of motor symptom improvement by long-term Tai Chi training in Parkinson's disease patients. Li Gen,Huang Pei,Cui Shi-Shuang,Tan Yu-Yan,He Ya-Chao,Shen Xin,Jiang Qin-Ying,Huang Ping,He Gui-Ying,Li Bin-Yin,Li Yu-Xin,Xu Jin,Wang Zheng,Chen Sheng-Di Translational neurodegeneration BACKGROUND:Tai Chi has been shown to improve motor symptoms in Parkinson's disease (PD), but its long-term effects and the related mechanisms remain to be elucidated. In this study, we investigated the effects of long-term Tai Chi training on motor symptoms in PD and the underlying mechanisms. METHODS:Ninety-five early-stage PD patients were enrolled and randomly divided into Tai Chi (n = 32), brisk walking (n = 31) and no-exercise (n = 32) groups. At baseline, 6 months and 12 months during one-year intervention, all participants underwent motor symptom evaluation by Berg balance scale (BBS), Unified PD rating-scale (UPDRS), Timed Up and Go test (TUG) and 3D gait analysis, functional magnetic resonance imaging (fMRI), plasma cytokine and metabolomics analysis, and blood Huntingtin interaction protein 2 (HIP2) mRNA level analysis. Longitudinal self-changes were calculated using repeated measures ANOVA. GEE (generalized estimating equations) was used to assess factors associated with the longitudinal data of rating scales. Switch rates were used for fMRI analysis. False discovery rate correction was used for multiple correction. RESULTS:Participants in the Tai Chi group had better performance in BBS, UPDRS, TUG and step width. Besides, Tai Chi was advantageous over brisk walking in improving BBS and step width. The improved BBS was correlated with enhanced visual network function and downregulation of interleukin-1β. The improvements in UPDRS were associated with enhanced default mode network function, decreased L-malic acid and 3-phosphoglyceric acid, and increased adenosine and HIP2 mRNA levels. In addition, arginine biosynthesis, urea cycle, tricarboxylic acid cycle and beta oxidation of very-long-chain fatty acids were also improved by Tai Chi training. CONCLUSIONS:Long-term Tai Chi training improves motor function, especially gait and balance, in PD. The underlying mechanisms may include enhanced brain network function, reduced inflammation, improved amino acid metabolism, energy metabolism and neurotransmitter metabolism, and decreased vulnerability to dopaminergic degeneration. Trial registration This study has been registered at Chinese Clinical Trial Registry (Registration number: ChiCTR2000036036; Registration date: August 22, 2020). 10.1186/s40035-022-00280-7
    A Dance Program to Manage A Fatigue-Sleep Disturbance-Depression Symptom Cluster among Breast Cancer Patients Receiving Adjuvant Chemotherapy: A Feasibility Study. He Xiaole,Ng Marques S N,Wang Xiao,Guo Pingli,Li Lulu,Zhao Wenqian,Zhang Mengyue,So Winnie K W Asia-Pacific journal of oncology nursing Objective:Fatigue, sleep disturbance, and depression (FSD) are highly prevalent among breast cancer (BC) patients undergoing adjuvant chemotherapy, constituting a common symptom cluster (i.e., FSD cluster). Exercise is effective in relieving fatigue, alleviating sleep disturbance, and improving the quality of life (QoL) during adjuvant chemotherapy among these women. Therefore, this study aimed to assess the feasibility and acceptability of a dance program with social support elements for managing this symptom cluster. Methods:A prospective randomized controlled design combined with a semi-structured interview was utilized. Twenty consented eligible participants were randomly assigned to a dance group or an attention control group after baseline assessment but before chemotherapy. The feasibility of recruitment, retention, intervention, and data collection procedures and the acceptability of exercise modality, hospital-based instruction, and home-based practice were collected by retrieving information from research documents and interviews by the principal investigator 4 weeks after the start of intervention. Results:The recruitment and retention rates were 86.96% and 100.00%, respectively. Participants took about 30-40 min to complete the questionnaire. All the items were comprehensible. The baseline characteristics were comparable between groups, indicating that randomization was successful. The implementation procedure progressed smoothly. Dancing was considered interesting and easy, and participants would like to practice at home. Only minor adjustments would be needed for future studies. Conclusions:This study demonstrated that the proposed dance program was feasible and acceptable for BC patients in hospital and home settings. A full-scale study is warranted to examine its effects on managing the FSD cluster and promoting QoL. 10.4103/2347-5625.308677
    Patient-Reported Outcome Measure for Real-time Symptom Assessment in Women With Endometriosis: Focus Group Study. van Barneveld Esther,Lim Arianne,van Hanegem Nehalennia,Vork Lisa,Herrewegh Alexandra,van Poll Mikal,Manders Jessica,van Osch Frits,Spaans Wilbert,van Koeveringe Gommert,Vrijens Desiree,Kruimel Joanna,Bongers Marlies,Leue Carsten JMIR formative research BACKGROUND:Symptoms related to endometriosis have a significant impact on the quality of life, and symptoms often recur. The experience sampling method (ESM), a digital questioning method characterized by randomly repeated momentary assessments, has several advantages over traditionally used measurements, including the ability to assess the temporal relationship between variables such as physical, mental, and social factors. OBJECTIVE:The aim of this study is to develop an ESM tool for patients with endometriosis to accurately measure symptoms and their course over time, allowing for personalized treatment and adequate monitoring of treatment efficacy in individual patients. METHODS:On the basis of international guidelines, items from validated questionnaires were selected through a literature review and during focus groups and multidisciplinary expert meetings. Data analysis was conducted using ATLAS.ti (ATLAS.ti Scientific Software Development GmbH). The feasibility and usability of the newly developed momentary assessment tool were tested for 28 consecutive days in 5 patients with endometriosis-related pain symptoms. RESULTS:Momentary assessment items contained questions concerning endometriosis symptoms, general somatic symptoms, psychological symptoms, contextual information, and the use of food and medication. A morning questionnaire on sleep and sexuality was included. In a pilot study, the patients considered the tool easy to use but time consuming. The average compliance rate of momentary assessments was 37.8% (106/280), with the highest completion rate during the first week (39/70, 56%). Therefore, it is advisable to use the ESM for a maximum of 7 days. CONCLUSIONS:A new digital tool for endometriosis symptom assessment was developed using the ESM, which may help overcome the limitations of current retrospective questionnaires. After validation and testing, future studies will be planned to evaluate the use of this tool in a clinical setting in order to propose a personalized treatment plan for women with endometriosis. 10.2196/28782
    Symptom Clusters in Advanced Cancer Patients: An Empirical Comparison of Statistical Methods and the Impact on Quality of Life. Dong Skye T,Costa Daniel S J,Butow Phyllis N,Lovell Melanie R,Agar Meera,Velikova Galina,Teckle Paulos,Tong Allison,Tebbutt Niall C,Clarke Stephen J,van der Hoek Kim,King Madeleine T,Fayers Peter M Journal of pain and symptom management CONTEXT:Symptom clusters in advanced cancer can influence patient outcomes. There is large heterogeneity in the methods used to identify symptom clusters. OBJECTIVES:To investigate the consistency of symptom cluster composition in advanced cancer patients using different statistical methodologies for all patients across five primary cancer sites, and to examine which clusters predict functional status, a global assessment of health and global quality of life. METHODS:Principal component analysis and exploratory factor analysis (with different rotation and factor selection methods) and hierarchical cluster analysis (with different linkage and similarity measures) were used on a data set of 1562 advanced cancer patients who completed the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. RESULTS:Four clusters consistently formed for many of the methods and cancer sites: tense-worry-irritable-depressed (emotional cluster), fatigue-pain, nausea-vomiting, and concentration-memory (cognitive cluster). The emotional cluster was a stronger predictor of overall quality of life than the other clusters. Fatigue-pain was a stronger predictor of overall health than the other clusters. The cognitive cluster and fatigue-pain predicted physical functioning, role functioning, and social functioning. CONCLUSIONS:The four identified symptom clusters were consistent across statistical methods and cancer types, although there were some noteworthy differences. Statistical derivation of symptom clusters is in need of greater methodological guidance. A psychosocial pathway in the management of symptom clusters may improve quality of life. Biological mechanisms underpinning symptom clusters need to be delineated by future research. A framework for evidence-based screening, assessment, treatment, and follow-up of symptom clusters in advanced cancer is essential. 10.1016/j.jpainsymman.2015.07.013
    The effectiveness of a self-efficacy-enhancing intervention for Chinese patients with colorectal cancer: a randomized controlled trial with 6-month follow up. Zhang Meifen,Chan Sally Wai-chi,You Liming,Wen Yongshan,Peng Lifen,Liu Weiyan,Zheng Meichun International journal of nursing studies BACKGROUND:Colorectal cancer is a major public health problem. There is growing support for colorectal cancer survivors who are experiencing problems after cancer treatment to engage in self-management programs to reduce symptom distress. However, there is inconclusive evidence as to the effectiveness of such program especially in Asian region. OBJECTIVES:This study tested the effects of a six-month nurse-led self-efficacy-enhancing intervention for patients with colorectal cancer, compared with routine care over a six-month follow up. DESIGN:A randomized controlled trial with repeated measures, two-group design. SETTING:Three teaching hospitals in Guangzhou, China. PARTICIPANTS:One hundred and fifty-two Chinese adult patients with a diagnosis of colorectal cancer were recruited. The intervention group (n=76) received self-efficacy-enhancing intervention and the control group (n=76) received standard care. METHOD:The participants were randomized into either intervention or control group after baseline measures. The outcomes of the study (self-efficacy, symptom distress, anxiety, depression and quality of life) were compared at baseline, three and six months after the intervention. RESULTS:Sixty-eight participants in the intervention group and 53 in the control group completed the study. Their mean age was 53 (SD=11.3). Repeated measure MANOVA found that the patients in the intervention group had significant improvement in their self-efficacy (F=7.26, p=0.003) and a reduction of symptom severity (F=5.30, p=0.01), symptom interference (F=4.06, p=0.025), anxiety (F=6.04, p=0.006) and depression (F=6.96, p=0.003) at three and six months, compared with the control group. However, no statistically significant main effect was observed in quality of life perception between the two groups. CONCLUSIONS:The nurse-led self-efficacy enhancing intervention was effective in promoting self-efficacy and psychological well-being in patients with colorectal cancer, compared with standard care. The intervention can be incorporated into routine care. Future empirical work is required to determine the longer term effects of the intervention. 10.1016/j.ijnurstu.2013.12.005
    Nutrition intervention is beneficial to the quality of life of patients with gastrointestinal cancer undergoing chemotherapy in Vietnam. Nguyen Linh Thuy,Dang Anh Kim,Duong Phuong Thi,Phan Hanh Bich Thi,Pham Chinh Tuyet Thi,Nguyen Anh Tuan Le,Le Huong Thi Cancer medicine INTRODUCTION:The best treatment therapy for gastrointestinal cancer patients is assessed by the improvement of health status and quality of life (QoL) after treatments. Malnutrition is related to loss of muscle strengths which leads to lower physical performance and emotional status. Thus, this study aimed to estimate the effects of nutritional interventions on the improvement of QoL among gastrointestinal patients undergoing chemotherapy in Vietnam. METHODS:A quasi-experiment with intervention and control groups for pre- and post-intervention assessment was carried out at the Department of Oncology and Palliative Care-Hanoi Medical University Hospital from 2016 to 2019. Sixty gastrointestinal cancer patients were recruited in each group. The intervention regimen consisted of nutritional counseling, a specific menu with a recommended amount of energy, protein, and formula milk used within 2 months. Nutritional status and QoL of patients were evaluated using The Scored Patient-Generated Subjective Global Assessment (PG-SGA) and The European Organization for Research and Treatment of Cancer (EORTC). The difference in differences (DiD) method was utilized to estimate the outcome between control and intervention groups. RESULTS:After the intervention, patients of the intervention group had better changes in scores of global health status (Coef =16.68; 95% CI =7.90; 25.46), physical (Coef =14.51; 95% CI =5.34; 23.70), and role functioning (Coef =14.67; 95% CI =1.63; 27.70) compared to the control group. Regarding symptom scales, the level of fatigue, pain, and insomnia symptoms significantly reduced between pre- and post-intervention in the intervention group. In addition, living in urban areas, defined as malnourished and having low prealbumin levels, were positively associated with the lower global health status/QoL score. CONCLUSION:Nutritional therapy with high protein was beneficial to the improvement in QoL, physical function and the reduction of negative symptoms among gastrointestinal cancer patients. Early individualized nutritional support in consultation with professional dietitians during chemotherapy plays an integral part in enhancing the QoL and better treatment prognosis. CLINICAL TRIAL REGISTRATION NUMBER:NCT04517708. 10.1002/cam4.3766
    Modeling symptom drivers of oral intake in long-term head and neck cancer survivors. Kamal Mona,Barrow Martha P,Lewin Jan S,Estrella Alicia,Gunn G Brandon,Shi Quiling,Hofstede Theresa M,Rosenthal David I,Fuller Clifton David,Hutcheson Katherine A, Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:This study examined the relationship between self-reported symptom severity and oral intake in long-term head and neck cancer (HNC) survivors. METHODS:An observational survey study with retrospective chart abstraction was conducted. HNC patients who had completed an MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) questionnaire and also had clinician graded oral intake ratings (Functional Oral Intake Scale [FOIS]) were included. Correlation coefficients were computed. FOIS scores were regressed on MDASI-HN symptom items using stepwise backwards elimination for multivariate models. RESULTS:One hundred and fifty-two survey pairings were included in the analysis (median 44 months follow-up, range 7-198). Per FOIS, 28% of survivors maintained a total oral diet with no restrictions, 67% reported a restricted oral diet (without tube), 3% were partially tube-dependent with some oral intake, and 2% were NPO. Of the 22 symptom items, the most severe items in decreasing order were dry mouth, difficulty swallowing\chewing, problems with mucus, tasting food, and choking/coughing. Significant bivariate correlations, after Bonferroni correction for multiple comparisons, were present for 8 of 22 symptoms with FOIS. On multivariate analysis, symptom severity for difficulty swallowing and problems with teeth/gums remained significantly associated with FOIS. CONCLUSIONS:Oral intake in HNC survivorship is a multidimensional issue and functional outcome that is impacted not only by dysphagia but also by dental status. Symptom drivers of oral intake likely differ in acute survivorship. Nonetheless, these findings highlight the lack of specificity in this end point and also the need for multidisciplinary supportive care to optimize oral intake in survivors. 10.1007/s00520-018-4434-4
    Feasibility and Preliminary Efficacy of a Bright Light Intervention in Ovarian and Endometrial Cancer Survivors. Fox Rina S,Baik Sharon H,McGinty Heather,Garcia Sofia F,Reid Kathryn J,Bovbjerg Katrin,Fajardo Precilla,Wu Lisa M,Shahabi Shohreh,Ong Jason C,Zee Phyllis C,Penedo Frank J International journal of behavioral medicine BACKGROUND:Cancer-related sleep disturbance is common and can adversely affect physical and mental health. Bright light (BL) therapy is a novel intervention that targets sleep by promoting circadian regulation. Emerging evidence suggests BL can improve sleep disturbance, symptom burden, and health-related quality of life in cancer and other populations; however, this research is limited. The present two-phase pilot study assessed the feasibility and preliminary intended effects of BL therapy on sleep in ovarian and endometrial cancer survivors, and explored biologic and chronobiologic factors that may underlie intervention effects. METHODS:In phase I, focus groups were conducted with 12 survivors and 9 gynecologic oncology clinicians to evaluate and gather feedback about the proposed study. In phase II, a pilot randomized controlled trial was conducted with 18 ovarian or endometrial cancer survivors who were randomized 1:1 to receive 45 min of BL or dim light (DL) for 4 weeks. Participants wore wrist actigraphs; completed sleep diaries and self-report questionnaires; and provided blood, saliva, and urine samples at baseline (T1), post-intervention (T2), and 3-month follow-up (T3). RESULTS:Study procedures were modified according to focus group results. Enrollment, retention, and adherence were all ≥ 80%. Mixed-model ANOVAs demonstrated that the number of nighttime awakenings per actigraphy, and sleep quality and depression per self-report, trended toward improvements in the BL condition compared to the DL condition. These variables improved from T1 to T2 before returning to baseline at T3. Effect sizes were generally medium to large. CONCLUSIONS:Study findings suggest that BL therapy is feasible among ovarian and endometrial cancer survivors. It may be an effective, non-pharmacological approach to reduce sleep disturbance and symptom burden in this population. 10.1007/s12529-020-09861-0
    Characteristics of symptom distress in Chinese nasopharyngeal carcinoma patients and its relation to mood disturbance: A cross-sectional study. Chen Yu,Chen Weichen,Yang Yuan,Zhao Yang,Yang Xueling European journal of cancer care OBJECTIVE:To evaluate the psychometric properties of a modified Chinese version of the Symptom Distress Scale (SDS), to explore symptom distress and its association with mood disturbance and factors that related to levels of symptom distress and mood disturbance. METHODS:A cross-sectional, correlation design was adopted. A convenience sample of 190 nasopharyngeal carcinoma (NPC) patients was recruited from a Cancer Center in Guangzhou, China, with 169 patients completing the study. RESULTS:The psychometric properties of the modified SDS were satisfactory (Cronbach's α = 0.80) with test-retest reliability (correlation coefficient = 0.71). Education, marital status, disease stage and SDS scores were significant influencing factors of mood disturbance. The overall symptom distress level of NPC patients was higher than that of other cancer groups, with dry mouth being the most distressing symptom. Symptom distress level was influenced by age, marital status, disease stage, treatment modality and number of radiotherapy (RT) sessions. CONCLUSION:More pain and symptom management care should be focused on patients who are older, single or divorced patients, those with late-stage disease, and those subjected to multimodality therapy. Symptom distress was the most significant influencing factor of NPC patients' mood status. 10.1111/ecc.13032
    Identification of Symptom Clusters and Their Influencing Factors in Subgroups of Chinese Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Yang Zhenjiao,Cui Miaoling,Zhang Xiaofang,Bai Jing,Tang Lian,Tan Guirong,Jiang Yun Journal of pain and symptom management CONTEXT:Limited studies have identified symptom clusters (SCs) and their risk factors and the relationships with inflammatory biomarkers in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). OBJECTIVES:In this study, we aimed to investigate SCs in patients with AECOPD and explore their influencing factors and relationships with inflammatory biomarkers. METHODS:Data were collected with sociodemographic and disease information questionnaires, and symptoms were measured with the revised Memorial Symptom Assessment Scale. SCs were extracted through exploratory factor analysis. Logistic regression analysis was conducted to explore the risk factors of SCs. RESULTS:A total of 151 patients were recruited. Two SCs, namely, emotional and respiratory functional SCs, were identified. Logistic regression analysis showed that individuals with high C-reactive protein level, Charlson Comorbidity Index score, and high modified Medical Research Council Dyspnea Scale score were more likely to belong to the high-severity symptom subgroup than to the low-severity symptom group in the emotional SC. The patients with a low body mass index and without or lax inhaled drug therapy exhibited highly prominent predictors of membership in the high-severity symptom group of the respiratory functional SC. CONCLUSION:Symptoms experienced by patients with AECOPD were grouped into specific clusters. Targeted interventions should be performed based on SCs, and influencing factors and biological mechanisms should be considered when providing individualized approaches and interventions. 10.1016/j.jpainsymman.2020.03.037
    Symptom Clusters, Physical Activity, and Quality of Life: A Latent Class Analysis of Children During Maintenance Therapy for Leukemia. Hooke Mary C,Mathiason Michelle A,Blommer Audrey,Hutter Jessica,Mitby Pauline,Taylor Olga,Scheurer Michael E,Kunin-Batson Alicia S,Pan Wei,Hockenberry Marilyn J Cancer nursing BACKGROUND:Children undergoing treatment for acute lymphocytic leukemia (ALL) report co-occurring symptoms of fatigue, sleep disturbances, and depression as a symptom cluster. Physical activity (PA) may influence symptom severity and quality of life (QOL). OBJECTIVES:This study examined changes in symptoms and QOL during ALL maintenance in children categorized by symptom cluster and explored the influence of PA and symptoms on QOL. METHODS:Self-report of fatigue, sleep disturbance, and depression; QOL; and PA were measured at the beginning and end of maintenance in 42 children aged 3 to 18 years with ALL. Children were categorized into symptom cluster groups based on measurements at the beginning of maintenance. RESULTS:Two latent classes of symptom clusters (low and high) were identified with significant differences between groups in symptoms at both the beginning and end maintenance (P < .01). Each group's symptom levels did not change during maintenance. Quality-of-life was different between groups at both time points (P < .01) and did not improve. Children with low symptoms and high PA at the beginning of maintenance had better QOL as treatment ended compared with the physically active high-symptom group and the inactive high-symptom group (P < .01). CONCLUSIONS:Children with higher symptoms did not experience an improvement with time. Symptom and PA levels may influence QOL at the end of treatment. IMPLICATIONS FOR PRACTICE:Maintenance therapy is a long time (1.5 years) in a child's life. Symptom assessment is needed early in maintenance; interventions are needed for children with high levels. 10.1097/NCC.0000000000000963
    User-Centered Design of a Mobile Health Intervention to Enhance Exacerbation-Related Self-Management in Patients With Chronic Obstructive Pulmonary Disease (Copilot): Mixed Methods Study. Korpershoek Yvonne J G,Hermsen Sander,Schoonhoven Lisette,Schuurmans Marieke J,Trappenburg Jaap C A Journal of medical Internet research BACKGROUND:Adequate self-management skills are of great importance for patients with chronic obstructive pulmonary disease (COPD) to reduce the impact of COPD exacerbations. Using mobile health (mHealth) to support exacerbation-related self-management could be promising in engaging patients in their own health and changing health behaviors. However, there is limited knowledge on how to design mHealth interventions that are effective, meet the needs of end users, and are perceived as useful. By following an iterative user-centered design (UCD) process, an evidence-driven and usable mHealth intervention was developed to enhance exacerbation-related self-management in patients with COPD. OBJECTIVE:This study aimed to describe in detail the full UCD and development process of an evidence-driven and usable mHealth intervention to enhance exacerbation-related self-management in patients with COPD. METHODS:The UCD process consisted of four iterative phases: (1) background analysis and design conceptualization, (2) alpha usability testing, (3) iterative software development, and (4) field usability testing. Patients with COPD, health care providers, COPD experts, designers, software developers, and a behavioral scientist were involved throughout the design and development process. The intervention was developed using the behavior change wheel (BCW), a theoretically based approach for designing behavior change interventions, and logic modeling was used to map out the potential working mechanism of the intervention. Furthermore, the principles of design thinking were used for the creative design of the intervention. Qualitative and quantitative research methods were used throughout the design and development process. RESULTS:The background analysis and design conceptualization phase resulted in final guiding principles for the intervention, a logic model to underpin the working mechanism of the intervention, and design requirements. Usability requirements were obtained from the usability testing phases. The iterative software development resulted in an evidence-driven and usable mHealth intervention-Copilot, a mobile app consisting of a symptom-monitoring module, and a personalized COPD action plan. CONCLUSIONS:By following a UCD process, an mHealth intervention was developed that meets the needs and preferences of patients with COPD, is likely to be used by patients with COPD, and has a high potential to be effective in reducing exacerbation impact. This extensive report of the intervention development process contributes to more transparency in the development of complex interventions in health care and can be used by researchers and designers as guidance for the development of future mHealth interventions. 10.2196/15449
    Nurse-Delivered Symptom Assessment for Individuals With Advanced Lung Cancer. Flannery Marie,Stein Karen F,Dougherty David W,Mohile Supriya,Guido Joseph,Wells Nancy Oncology nursing forum OBJECTIVES:To assess an intervention derived from self-regulation theory (SRT) to promote well-being for individuals with advanced lung cancer. SAMPLE &AMP; SETTING:45 adults with advanced lung cancer who were receiving chemotherapy at an ambulatory cancer center. METHODS &AMP; VARIABLES:Participants were randomized to the intervention group or usual care control group. Feasibility assessment focused on recruitment, retention, design, methods, and fidelity. Outcome measures of quality of life, symptoms, and distress were collected at four time points. The main research variables were symptoms, quality of life, and distress. RESULTS:The participation rate was 79%, and the retention rate was 62%. Participant loss was most often because of progressive disease and occurred early in the study. High fidelity was noted for delivery of the intervention as planned and outcome data collection by telephone. The mean number of interventions delivered was 5.5 of a planned 8. A high level of acceptability was reported for participants completing the intervention. IMPLICATIONS FOR NURSING:Although delivering the SRT-derived intervention with fidelity was possible, feasibility findings do not warrant intervention replication in this population. 10.1188/18.ONF.619-630
    Longitudinal health utility and symptom-toxicity trajectories in patients with head and neck cancers. Cancer BACKGROUND:This study examined long-term health utility and symptom-toxicity trajectories among patients with head and neck cancer (HNC). METHODS:For patients diagnosed with HNC (2014-2019), Health Utility Index 3 (HUI-3), Edmonton Symptom Assessment Scale (ESAS), and MD Anderson Symptom Inventory (MDASI) surveys (including both the core and head and neck cancer modules) were prospectively collected at multiple time points (at the baseline, after surgery, during radiotherapy, and 3, 6, 12, and 24 months after treatment). Locally estimated scatterplot smoothing plots were generated to describe HUI-3, ESAS, and MDASI trajectories over time by clinicodemographic factors, treatment modality, and tumor subsite. Contributions of clinical factors were assessed with univariable and multivariable analyses. RESULTS:In 800 patients, the treatment modality and the tumor subsite produced unique HUI-3, ESAS, and MDASI trajectories. Patients treated with surgery alone experienced rapid improvements in HUI-3, ESAS, and MDASI scores postoperatively. Among patients treated with chemoradiotherapy, patients with nasopharyngeal carcinoma had greater declines in HUI-3 during treatment in comparison with patients with oropharyngeal carcinoma, but they had similar ESAS/MDASI scores. Among patients treated with radiotherapy, patients with laryngeal carcinoma had better HUI-3/ESAS/MDASI scores than those with oropharyngeal carcinoma during treatment, but they slowly converged after treatment. Female sex, an age > 75 years, a household income < $40,000, a Charlson comorbidity score > 1, an Eastern Cooperative Oncology Group performance status > 0 (at the baseline), and current smoking were independently associated with worse HUI-3 trajectories. HUI-3 had mild to moderate correlations (ρ = 0.2-0.5) with individual symptom-toxicity trajectories. CONCLUSIONS:Long-term HUI-3 trajectories are associated with tumor subsite, clinicodemographic, and treatment factors, and this may be partly explained by relationships with symptoms/toxicities. Separate evaluations by subsite and treatment should occur in health utility and symptom-toxicity studies of HNC. LAY SUMMARY:This study indicates that the long-term health utility and symptoms/toxicities of patients with the most common head and neck cancers (ie, squamous cell carcinomas and nasopharyngeal carcinomas) differ over time with a variety of factors, including the tumor anatomic site, treatment volume, clinicodemographic characteristics (eg, age, human papillomavirus status, tumor stage, gender, smoking status, alcohol status, education, and comorbidities), and treatment modalities. Generalizations across all head and neck cancers should be strongly discouraged. Future studies should evaluate health utility, symptoms and toxicities, and patient need assessments separately for each anatomic site and treatment modality. 10.1002/cncr.33936
    Should we cluster patients or symptoms? The myth of symptom clusters based on 'depression, insomnia, pain' and 'depression, fatigue, pain'. Aktas Aynur,Walsh Declan,Hauser Katherine,Rybicki Lisa BMJ supportive & palliative care CONTEXT:'Depression, fatigue, pain' (DFP) and 'depression, insomnia, pain' (DIP) symptom clusters (SCs) have been proposed in cancer. These symptoms are common and co-occur, that is, they constitute clusters of patients rather than symptoms. OBJECTIVES:The following research questions were addressed: (1) What is the frequency of co-occurrence of two symptom groups (DFP and DIP) in advanced cancer? (2) What is the degree of symptom item association within each symptom group? (3) Were either of these symptom trios associated with prognosis? METHODS:We reanalysed a symptom data set of 1000 patients with advanced cancer. We identified the frequency of co-occurrence of two symptom groups: DFP and DIP, using both prevalence and severity data. The symptom associations were tested by χ(2) and Spearman correlations. We also determined whether either of these symptom trios were associated with a major biological outcome, that is, survival by time-to-event analyses. RESULTS:(1) Although DFP and DIP co-occured in about a quarter of the population, they were not SCs, but rather patient clusters. (2) Many persons had only one symptom from any symptom pair, and correlation coefficients were low for all symptom pairs. (3) Neither DFP nor DIP were associated with survival. CONCLUSIONS:Neither DFP nor DIP symptom item combinations constituted a specific cancer SC contrary to prior reports. DFP co-occurred in 27% and DIP in only 20%. Additionally, these symptom combinations were not associated with a biological outcome, that is, poor prognosis. Patient subgroups identified by shared symptom experiences alone do not identify SCs. 10.1136/bmjspcare-2015-000896
    Uncertainty levels differ by physical heart failure symptom cluster. Sethares Kristen A,Viveiros Jennifer D,Ayotte Brian Applied nursing research : ANR BACKGROUND:The role of uncertainty, unpredictable symptoms, and unknown illness trajectory are frequent concerns reported in heart failure (HF) literature. Illness uncertainty can lead to difficulty interpreting symptoms, potentially impacting outcomes. Impaired functional status, quality of life, all-cause mortality, rehospitalization, and event-free survival are predicted by symptom clusters. No studies to date describe levels of uncertainty by physical symptom cluster in HF. AIMS:Describe physical HF symptom clusters and determine if uncertainty levels differ by symptom cluster. METHODS:Results are based on a secondary analysis of data from patients hospitalized with an acute exacerbation of HF. The Heart Failure Somatic Perception Scale (HFSPS) and Mishel's Uncertainty in Illness Scale (MUIS-C) were completed. Symptom clusters were determined by hierarchical agglomerative clustering. Controlling for age and gender, ANCOVA (post hoc LSD) analyses explored uncertainty levels by symptom cluster group. RESULTS:One hundred and thirty-three primarily older (76.4 ± 12.1), Caucasian (92.5%) adults (55.2% male), with an ischemic HF etiology (71.6%) were enrolled. Three clusters were found: 1. Shortness of breath, n = 47, 2. Edema, n = 39, and 3. Cardiac, n = 43. Adjusting for age and gender, uncertainty levels differed by cluster group (p ≤ 0.001), with edema cluster members reporting greater illness uncertainty than cardiac cluster members (74.6 vs 69.5, respectively, p = 0.033). CONCLUSIONS:Differences exist in illness uncertainty levels based on the symptom experience of patients with HF. Care and management of HF symptoms should include a complete assessment of unique symptom cluster profiles. 10.1016/j.apnr.2021.151435
    Feasibility and potential effects of tai chi for the fatigue-sleep disturbance-depression symptom cluster in patients with breast cancer: protocol of a preliminary randomised controlled trial. Yao Li-Qun,Tan Jing-Yu Benjamin,Turner Catherine,Wang Tao BMJ open INTRODUCTION:The fatigue-sleep disturbance-depression symptom cluster (FSDSC) is one of the most common and debilitating side effects in patients with breast cancer (BC) throughout their treatment trajectory. Tai chi has been supported as a promising non-pharmacological intervention for the individual symptom relief of cancer-related fatigue, sleep disturbance and depression. However, relevant evidence of using tai chi for FSDSC management in patients with BC has been lacking. METHODS:This study will be a two-arm, single-blinded pilot randomised controlled trial involving an 8-week intervention and a 4-week follow-up. Seventy-two patients with BC experiencing the FSDSC will be recruited from two tertiary medical centres in China. The participants will be randomised to either a tai chi group (n=36) or a control group (n=36). The participants in the tai chi group will receive an 8-week tai chi intervention in addition to standard care, while the participants in the control group will receive standard care only consisting of a booklet on the self-management of cancer symptoms. The primary outcomes will include a series of feasibility assessments of the study protocol in relation to the study's methodological procedures, including subject recruitment and follow-up process, completion of study questionnaires and the feasibility, acceptability and safety of the intervention. The secondary outcomes will be the clinical outcomes regarding the effects of tai chi on the FSDSC and quality of life, which will be evaluated by the Brief Fatigue Inventory, the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale and the Functional Assessment of Cancer Therapy-Breast questionnaires. ETHICS AND DISSEMINATION:Ethics approval was obtained from relevant sites (H19094, KY2019133, 201932). The findings of the study will be published in peer-reviewed scientific journals and at conferences. TRAIL REGISTRATION NUMBER:NCT04190342; Pre-results. 10.1136/bmjopen-2020-048115
    Optimising symptom management in children with cancer using a novel mobile phone application: protocol for a controlled hybrid effectiveness implementation trial (RESPONSE). Bradford Natalie,Condon Paula,Pitt Erin,Tyack Zephanie,Alexander Kimberly BMC health services research BACKGROUND:Intense and aggressive treatment regimens for most children's cancer have achieved vast improvements in survival but are also responsible for both a high number and burden of symptoms. The use of Patient Reported Outcome Measures (PROMs) demonstrates a range of benefits for improved symptom management in adults with cancer. There are, however, multiple barriers to integrating PROMs into routine care in children and adolescents with cancer. This study aims to evaluate: (1) the effectiveness of electronic PROMs to generate stratified alerts, symptom management recommendations and graphical summaries (the RESPONSE system) to improve health outcomes and (2) the implementation of the RESPONSE system by assessing feasibility, acceptability, satisfaction, and sustainability. METHODS:A pragmatic hybrid II effectiveness-implementation controlled trial, using mixed methods, will be undertaken, advancing both knowledge of the effectiveness of the intervention and implementation factors. One-hundred and sixty children with cancer receiving active treatment will be recruited 1:1 to a non-randomised study involving two groups with an equal number of participants in each group. The intervention group (n = 80) will be prospectively recruited to receive the RESPONSE system intervention over eight weeks, versus the historical matched control group (n = 80) who will complete the ePROMs without access to the RESPONSE system. The primary outcome of the effectiveness trial is change between groups in total symptom burden. Secondary outcomes include child health-related quality-of-life and implementation outcomes. Trial data will be analysed using linear mixed-effects models. Formative implementation evaluation is informed by CFIR and ERIC frameworks and implementation outcomes will be mapped to the RE-AIM framework and include interviews, field notes, as well as administrative data to evaluate feasibility, acceptability, satisfaction and sustainability. TRIAL REGISTRATION NUMBER:ACTRN12621001084875 . Retrospectively Registered 16 August 2021. 10.1186/s12913-021-06943-x
    An update in symptom clusters using the Edmonton Symptom Assessment System in a palliative radiotherapy clinic. Ganesh Vithusha,Zhang Liying,Chan Stephanie,Wan Bo Angela,Drost Leah,Tsao May,Danjoux Cyril,Barnes Elizabeth,McDonald Rachel,Rowbottom Leigha,Zaki Pearl,Chow Ronald,Hwang Matthew K,DeAngelis Carlo,Lao Nicholas,Chow Edward Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:To identify symptom clusters in advanced cancer patients attending a palliative radiotherapy clinic using the Edmonton Symptom Assessment System (ESAS). METHODS:Principal component analysis (PCA), exploratory factor analysis (EFA), and hierarchical cluster analysis (HCA) were used to identify symptom clusters among the nine ESAS items using scores from each patient's first visit. RESULTS:ESAS scores from 182 patients were analyzed. The PCA identified three symptom clusters (cluster 1: depression-anxiety-well-being, cluster 2: pain-tiredness-drowsiness, cluster 3: nausea-dyspnea-loss of appetite). The EFA identified two clusters (cluster 1: tiredness-drowsiness-loss of appetite-well-being-pain-nausea-dyspnea, cluster 2: depression-anxiety). The HCA identified three clusters similar to the PCA with an exception of the loss of appetite item being classified under cluster 1 rather than 3. Two to three symptom clusters were identified using three analytical methods, with similar patterns reported in the literature. Particular groups of items co-occurred consistently across all three analyses: depression and anxiety; nausea and dyspnea; as well as pain, tiredness, and drowsiness. CONCLUSION:Three similar symptom clusters were identified in our patient population using the PCA and HCA; whereas, the EFA produced two clusters: one physical and one psychological cluster. Given the implications of symptom clusters in the management of quality of life, clinicians should be aware of these clusters to aid in the palliative treatment of patients. 10.1007/s00520-017-3749-x
    Utility of a Patient-Reported Symptom and Functioning Assessment Tool for Geriatric Oncology Care in China. Value in health regional issues OBJECTIVES:Symptom and functional assessment is challenging in geriatric oncology care. This multicenter cross-sectional study examined the use of a multiple-symptom assessment tool, the MD Anderson Symptom Inventory (MDASI), on Chinese patients with cancer aged 65 years and older. METHODS:Patient-rated symptoms and functioning were assessed using MDASI and the European Organization for Research and Treatment of Cancer quality-of-life questionnaire. RESULTS:The most severe symptoms were fatigue and poor appetite. The older group (75-84 years old, n = 224) reported a more severe difficulty remembering (effect size [ES] 0.32; P < .001), shortness of breath (ES 0.20; P = .020), and interference with general activity (ES 0.14; P = .027), with significantly worse physical functioning (ES -0.33; P < .001) and cognitive functioning on the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (ES 0.20; P < .001) than the younger group (65-74 years old, n = 555). For MDASI measures of the core symptoms and total interference with daily activity, Cronbach α coefficients were 0.90 and 0.93, respectively, for the younger group; and 0.93 and 0.94 for the older group, respectively. Moderate to severe (score ≥4) interference with general activity and walking on MDASI accurately indicated poor performance status (area under the curve 0.8089 and 0.7969, respectively) and lack of independence status of Activities of Daily Living (area under the curve 0.7993 and 0.8304, respectively). CONCLUSIONS:MDASI is psychometrically reliable, valid, and clinically sensitive for the measuring symptom burden and functional status of Chinese patients with cancer aged 65 years and older. MDASI could be adopted to measure multiple symptoms and physical functioning outcomes in geriatric oncology practice as well as for research on treatment benefits. 10.1016/j.vhri.2021.08.001
    Does Symptom Recognition Improve Self-Care in Patients with Heart Failure? A Pilot Study Randomised Controlled Trial. Pereira Sousa Joana,Neves Hugo,Pais-Vieira Miguel Nursing reports (Pavia, Italy) Patients with heart failure have difficulty in self-care management, as daily monitoring and recognition of symptoms do not readily trigger an action to avoid hospital admissions. The purpose of this study was to understand the impact of a nurse-led complex intervention on symptom recognition and fluid restriction. A latent growth model was designed to estimate the longitudinal effect of a nursing-led complex intervention on self-care management and quality-of-life changes in patients with heart failure and assessed by a pilot study performed on sixty-three patients (33 control, 30 intervention). Patients in the control group had a higher risk of hospitalisation (IRR 11.36; < 0.001) and emergency admission (IRR 4.24; < 0.001) at three-months follow-up. Analysis of the time scores demonstrated that the intervention group had a clear improvement in self-care behaviours (βSlope. Assignment_group = -0.881; < 0.001) and in the quality of life (βSlope. Assignment_group = 1.739; < 0.001). This study supports that a nurse-led programme on symptom recognition and fluid restriction can positively impact self-care behaviours and quality of life in patients with heart failure. This randomised controlled trial was retrospectively registered (NCT04892004). 10.3390/nursrep11020040
    Factors associated with symptom distress in women with breast cancer prior to initiation of chemotherapy. Mazanec Susan R,Park Sumin,Connolly Mary C,Rosenzweig Margaret Quinn Applied nursing research : ANR BACKGROUND:Symptom distress in women with breast cancer is associated with early discontinuation of chemotherapy and may influence treatment outcomes. Describing racial differences in prechemotherapy symptom distress and examining contextual variables of the symptom experience may inform our understanding of the complex problem of racial disparities in breast cancer. AIM:To determine if perceived social support, healthcare system distrust, and economic hardship predict symptom distress in women with breast cancer prior to their first chemotherapy treatment. DESIGN:Descriptive, correlational, cross-sectional. METHODS:Baseline data (N = 119) was used from a multisite, longitudinal study comparing the symptom experience and ability to receive chemotherapy of Black and White women with breast cancer (R01MD012245; Rosenzweig, PI). Measures included the Symptom Distress Scale, Interpersonal Support Evaluation List, Health Care System Distrust Scale, and Psychological Sense of Economic Hardship scale. The analysis consisted of multiple regression and a t-test. RESULTS:On average, participants reported five symptoms prior to chemotherapy. Black women reported higher symptoms distress than White women; t(68.34) = 2.15, p = 0.035. The model explained 26% of variance in symptom distress; F(5, 112) = 9.01, p < 0.001. While controlling for age and race, greater perceived economic hardship contributed to higher symptom distress (β = 0.36, p = 0.001, 95% CI: 0.34 to 1.34). Race, health care system distrust and social support did not significantly predict symptom distress. CONCLUSION:Assessment of perceived financial hardship prior to beginning chemotherapy is critical to identify those patients at risk for greater symptom distress. 10.1016/j.apnr.2021.151515
    Atrial fibrillation symptom clusters and associated clinical characteristics and outcomes: A cross-sectional secondary data analysis. European journal of cardiovascular nursing BACKGROUND:Symptom clusters among adults with atrial fibrillation have previously been identified but no study has examined the relationship between symptom clusters and outcomes. AIMS:The purpose of this study was to identify atrial fibrillation-specific symptom clusters, characterize individuals with each cluster, and determine whether symptom cluster membership is associated with healthcare utilization. METHODS:This was a cross-sectional secondary data analysis of 1501 adults from the Vanderbilt Atrial Fibrillation Registry with verified atrial fibrillation. Self-reported symptoms were measured with the University of Toronto Atrial Fibrillation Severity Scale. We used hierarchical cluster analysis (Ward's method) to identify clusters and dendrograms, pseudo F, and pseudo T-squared to determine the ideal number of clusters. Next, we used regression analysis to examine the association between cluster membership and healthcare utilization. RESULTS:Males predominated (67%) and the average age was 58.4 years. Two symptom clusters were identified, a Weary cluster (3.7%, n=56, fatigue at rest, shortness of breath at rest, chest pain, and dizziness) and an Exertional cluster (32.7%, n=491, shortness of breath with activity and exercise intolerance). Several sociodemographic and clinical characteristics varied by symptom cluster group membership, including age, gender, atrial fibrillation type, body mass index, comorbidity status, and treatment strategy. Women were more likely to experience either cluster ( p<0.001). The Weary cluster was associated with nearly triple the rate of emergency department utilization (incident rate ratio [IRR] 2.8, p<0.001) and twice the rate of hospitalizations (IRR 1.9, p<0.001). CONCLUSION:We identified two symptom clusters. The Weary cluster was associated with a significantly increased rate of healthcare utilization. 10.1177/1474515118778445
    Advancing Symptom Science Through Symptom Cluster Research: Expert Panel Proceedings and Recommendations. Miaskowski Christine,Barsevick Andrea,Berger Ann,Casagrande Rocco,Grady Patricia A,Jacobsen Paul,Kutner Jean,Patrick Donald,Zimmerman Lani,Xiao Canhua,Matocha Martha,Marden Sue Journal of the National Cancer Institute An overview of proceedings, findings, and recommendations from the workshop on "Advancing Symptom Science Through Symptom Cluster Research" sponsored by the National Institute of Nursing Research (NINR) and the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, is presented. This workshop engaged an expert panel in an evidenced-based discussion regarding the state of the science of symptom clusters in chronic conditions including cancer and other rare diseases. An interdisciplinary working group from the extramural research community representing nursing, medicine, oncology, psychology, and bioinformatics was convened at the National Institutes of Health. Based on expertise, members were divided into teams to address key areas: defining characteristics of symptom clusters, priority symptom clusters and underlying mechanisms, measurement issues, targeted interventions, and new analytic strategies. For each area, the evidence was synthesized, limitations and gaps identified, and recommendations for future research delineated. The majority of findings in each area were from studies of oncology patients. However, increasing evidence suggests that symptom clusters occur in patients with other chronic conditions (eg, pulmonary, cardiac, and end-stage renal disease). Nonetheless, symptom cluster research is extremely limited and scientists are just beginning to understand how to investigate symptom clusters by developing frameworks and new methods and approaches. With a focus on personalized care, an understanding of individual susceptibility to symptoms and whether a "driving" symptom exists that triggers other symptoms in the cluster is needed. Also, research aimed at identifying the mechanisms that underlie symptom clusters is essential to developing targeted interventions. 10.1093/jnci/djw253
    Developing and Evaluating a Self-Management Intervention for Women With Breast Cancer. Goldberg Jessica,Hinchey Jenna,Feder Shelli,Schulman-Green Dena Western journal of nursing research Reports of self-management interventions usually focus on efficacy and do not detail processes of intervention development and evaluation. We describe the development and evaluation of Managing Cancer Care: A Personal Guide, a patient-oriented cancer self-management intervention consisting of seven modules on the topics of self-management, care options, transitions, communication, symptom management, and self-efficacy. We developed and evaluated the intervention in stages by partnering with women with breast cancer. Stages were as follows: individual interviews (n = 25), intervention design, focus group (n = 6), pilot testing with metastatic patients (n = 23), and population testing with non-metastatic patients (n = 105). We used interpretive description and content analysis for qualitative analyses and used descriptive statistics to analyze module ratings and frequency of use. We report results of each stage and discuss the challenges of creating a self-management intervention that has broad appeal without taking a one-size-fits-all approach and implementing a self-management intervention in a real-world versus research setting. 10.1177/0193945916650675
    The Effect of Watson's Human Caring Model on Meaning of Life and Symptom Management in Cancer Patients Undergoing Chemotherapy. Aktürk Ümmühan,Erci Behice Research and theory for nursing practice PURPOSE:The purpose of this study was to determine the effect of Watson's Human Caring Model on the meaning of life and symptom management in cancer patients undergoing chemotherapy. DESIGN:The study was conducted using a real test model featuring a pretest and posttest and a control group. METHODS:The sample consisted of 158 adult cancer patients (79 in both the experimental and control groups). The sample size was determined and the participants were allocated to groups using power analysis and a random sampling method. For the pretest, both groups completed an introductory questionnaire, the Life Attitude Profile, and the General Symptom Inventory. Then, the experimenter visited the experimental group patients' homes three times, at 2-week intervals, to provide nursing care based on Watson's model. Finally, after 8 weeks, a posttest was conducted by having both groups complete the Life Attitude Profile and General Symptom Inventory once again. RESULTS:In the experimental group, the mean total posttest score for the Life Attitude Profile was determined to be 164.21 ± 36.5, and the mean total General Symptom Inventory score was 55.06 ± 13.19; however, in the control group, the mean total Life Attitude Profile score was 127.31 ± 10.61 and the mean total General Symptom Inventory score was 136.91 ± 16.20. The mean differences between the groups were statistically significant ( < .001). IMPLICATIONS FOR PRACTICE:Care based on Watson's model increases the sense of meaning in life and decreases symptom levels for patients undergoing chemotherapy. 10.1891/1541-6577.32.3.255
    Caregiver-Reported Health Outcomes: Effects of Providing Reflexology for Symptom Management to Women With Advanced Breast Cancer. Frambes Dawn,Sikorskii Alla,Tesnjak Irena,Wyatt Gwen,Lehto Rebecca,Given Barbara Oncology nursing forum PURPOSE/OBJECTIVES:To determine the effects of delivering a reflexology intervention on health outcomes of informal caregivers, and to explore whether intervention effects are moderated by caregiver characteristics. 
. DESIGN:Two-group, randomized clinical trial.
. SETTING:Eight oncology clinics in urban and rural regions of Michigan and Illinois.
. SAMPLE:180 informal caregivers of patients with advanced breast cancer.
. METHODS:Caregivers were randomized to provide reflexology to individuals with cancer during a four-week period or to attention control. Data collection occurred at baseline and at weeks 5 and 11. Linear mixed-effects modeling was used to test intervention effects among all participants and the effects of the number of sessions delivered in the reflexology group.
. MAIN RESEARCH VARIABLES:Caregiver characteristics; psychological, physical, and social outcomes.
. FINDINGS:Caregiver fatigue in the reflexology group was reduced compared to controls at weeks 5 (p = 0.02) and 11 (p = 0.05). No differences were found for anxiety, depression, pain, physical function, sleep disturbance, satisfaction with participation in social roles, and pain interference between caregivers who delivered reflexology and those who did not.
. CONCLUSIONS:Informal caregivers who provided reflexology to individuals with cancer did not have negative psychological, physical, or social outcomes. Fatigue levels were lower among caregivers who provided reflexology. 
. IMPLICATIONS FOR NURSING:Clinicians need to be aware that providing supportive care interventions, such as reflexology, to reduce symptom burden does not increase negative outcomes on informal caregivers who provide this care, and it may even lead to reduced fatigue. 10.1188/17.ONF.596-605
    Do physical activity and social cognitive theory variable scores differ across symptom cluster severity groups in multiple sclerosis? Silveira Stephanie L,Cederberg Katie L J,Jeng Brenda,Sikes E Morghen,Sandroff Brian M,Jones Catherine D,Motl Robert W Disability and health journal BACKGROUND:Persons with multiple sclerosis (MS) experience co-occurring symptoms termed "symptom clusters" that can be distinguished based on mild, moderate, or severe symptom severity termed "symptom cluster severity." Physical activity (PA) may be an approach for improving co-occurring symptoms. OBJECTIVE:To examined if PA and social cognitive theory (SCT) variables differed by symptom cluster groups, and if associations between SCT variables and PA were moderated by symptom cluster groups. METHODS:Secondary analysis of participants with MS (N = 205) enrolled in a cross-sectional study. Trend analyses were conducted to determine if device-measured and self-reported PA and SCT variables (i.e., social support, self-efficacy, outcome expectations, goal setting, planning, and impediments) decreased with increased symptom cluster severity. Spearman rho rank-order correlations were conducted between PA measures and SCT variables within each symptom cluster group. RESULTS:Linear trend analyses indicated that self-reported PA declined with increased symptom cluster severity groups (F = 4.90,p = 0.03). Linear trend analyses indicated significant differences among symptom cluster severity groups in social support (F = 31.43,p = 0.001), exercise self-efficacy (F = 22.55,p = 0.001), barrier self-efficacy (F = 11.48,p = 0.001), outcome expectations (F = 6.98,p = 0.009), and impediments (F = 34.41,p = 0.001). There were differential associations of moderate magnitude in correlations, such that three SCT variables were associated with PA in the mild group (i.e., self-efficacy, goal setting and planning), two in the moderate group (i.e., social support and goal setting), and four in the severe group (i.e., self-efficacy, outcome expectations, planning, and social support). CONCLUSIONS:Further research is warranted examining the use of SCT-based behavior change techniques for promoting PA and improving symptom clusters in persons with MS. 10.1016/j.dhjo.2021.101163
    Gender differences in recovery outcomes after an early recovery symptom management intervention. Zimmerman Lani,Barnason Susan,Hertzog Melody,Young Lufei,Nieveen Janet,Schulz Paula,Tu Chunhao Heart & lung : the journal of critical care BACKGROUND:Despite known gender differences in recovery, few studies have examined symptom management (SM) interventions or responses by gender after coronary artery bypass surgery (CABS). OBJECTIVE:The purpose of this subanalysis was to describe and evaluate differences in response by gender to an SM intervention on the presence and burden of symptoms, physical activity, and physical functioning in elderly CABS patients during the early discharge period (3 and 6 weeks after CABS, and 3 and 6 months after CABS). METHODS:The parent study whose data were analyzed to examine gender differences involved a two-group, randomized clinical trial design. The 6-week early recovery SM telehealth intervention was delivered by the Health Buddy. Measures included the Cardiac Symptom Survey, a Modified 7-Day Activity Interview, an RT3 accelerometer, an Activity Diary, and the Medical Outcomes Study Short Form 36. This study was not powered for a gender × group analysis, and we used descriptive statistics, χ(2) tests, t tests, and analysis of variance for statistical analyses. RESULTS:Subjects (n = 232) included 192 men and 40 women, with a mean age of 71.2 SD, 7 years. The intervention group consisted of 86 men and 23 women, and the usual care (UC) group consisted of 106 men and 17 women. Data trends suggest that the SM intervention exerted greater impact on women than on men for symptoms such as fatigue, depression, sleep problems, and pain. Again, men exhibited higher levels of physical activity than did women. However, women in the SM group generally had higher scores than did women in the UC group. CONCLUSION:Although the parent study found no effect of an early recovery SM intervention, this exploratory secondary analysis indicated that women in the intervention group demonstrated more improvement in measures of physical activity than did those in the UC group. Further study, using a larger sample, is necessary to test these preliminary results. 10.1016/j.hrtlng.2010.07.018
    Clinical Observation on the Effect of Systematic Nursing Intervention on Cognitive Function, Life Activity Ability, and Quality of Life of Senile Dementia Patients. Evidence-based complementary and alternative medicine : eCAM OBJECTIVE:To explore the influence of systematic nursing intervention on the life ability and quality of senile dementia patients. METHODS:Total of 82 senile dementia patients who were admitted to our hospital from January 2018 to January 2020 were divided into two groups according to the random number table, and the nursing intervention was analyzed. 41 patients in the control group were given routine nursing care, and 41 patients in the observation group were given systematic nursing intervention. Patients were assessed cognitively using the Montreal Cognitive Assessment Scale (MoCA). The Barthel index and SF-36 were used to evaluate the patients' daily activity function and quality of life. A Symptom Checklist-90-Revised (SCL-90-R) was used to assess mental distress. The Social-Adaptive Function Rating Scale (SAFE) and Social Skills Inventory (SSC) were used to evaluate the patients' social interaction ability before and after nursing intervention. Nursing satisfaction was distributed to patients in the form of a self-prepared nursing satisfaction questionnaire for scoring. RESULTS:After the nursing intervention, the MoCA scores of patients in the two groups were higher than those before the nursing intervention, and the scores in the observation group were higher than those in the control group ( < 0.05). After the nursing intervention, the Barthel index scores of patients in the two groups were higher than those before the nursing intervention, and the scores in the observation group were higher than those in the control group ( < 0.05). After the nursing intervention, the SF-36 scores of patients in the two groups were higher than those before the nursing intervention, and the scores in the observation group were higher than those in the control group ( < 0.05). After nursing intervention, the SCL-90-R scores of patients in the two groups were lower than those before nursing intervention, and the scores in the observation group were lower than those in the control group ( < 0.05). After the nursing intervention, the SAFE scores of patients in the two groups were lower than those before the nursing intervention, and the safe scores of the observation group were lower than those of the control group ( < 0.05). After the nursing intervention, the SSC scores of patients in the two groups were lower than those before the nursing intervention, and the scores in the observation group were lower than those in the control group ( < 0.05). After nursing intervention, the total satisfaction degree of the control group (80.49%) was lower than that of the observation group (97.56%) ( < 0.05). CONCLUSION:The implementation of systematic nursing intervention is conducive to improve the cognitive function, activity of life, and quality of life of senile dementia patients who have a positive effect, and nursing satisfaction is higher. 10.1155/2021/2839142
    Psychometric evaluation of the Advanced Systemic Mastocytosis Symptom Assessment Form (AdvSM-SAF). Taylor Fiona,Li Xiaoran,Yip Christine,Padilla Brad,Mar Brenton,Green Tanya,Oren Ronny,Boral Anthony L,Lin Hui-Min,Shields Alan L,Gotlib Jason Leukemia research BACKGROUND:The Advanced Systemic Mastocytosis Symptom Assessment Form (AdvSM-SAF) was developed to evaluate symptoms of advanced systemic mastocytosis (AdvSM). This study aimed to psychometrically evaluate AdvSM-SAF scores and provide score interpretation guidelines. METHODS:The 10-item AdvSM-SAF was administered daily (scored as a seven-day average) in EXPLORER, an open-label Phase 1 study in AdvSM. Score distribution, reliability, construct-related validity, sensitivity to change, and interpretation guidelines were evaluated for AdvSM-SAF items, gastrointestinal symptom score (GSS), skin symptom score (SSS), and total symptom score (TSS). RESULTS:Thirty-one patients contributed to the analyses. At Baseline, the GSS, SSS, and TSS had adequate internal consistency (α > 0.7) and test-retest reliability (intraclass correlation coefficients >0.7). AdvSM-SAF scores were moderately to strongly correlated with variables as expected, and distinguished among clinically distinct groups. Observed relationships between change scores in the AdvSM-SAF and other assessments reflect evidence that AdvSM-SAF scores change in concert with other assessments designed to measure similar constructs. The magnitude of AdvSM-SAF weekly TSS mean change scores based on different anchor groupings was as expected (improvement > stable > worsening). Candidate clinically meaningful between-group difference estimates (GSS = 2-4, SSS = 2-3, and TSS = 4-7 points) and within-person change estimates (GSS = 6-9, SSS = 1-4, TSS = 9-14) for AdvSM-SAF weekly scores were generated. CONCLUSION:The AdvSM-SAF produced reliable, construct-valid, and sensitive scores when administered in the target patient population. These results, along with its strong development history and evidence of content validity, indicate that the AdvSM-SAF is fit for the purpose of measuring treatment benefit in individuals with AdvSM. 10.1016/j.leukres.2021.106606
    Barriers to cancer symptom presentation among people from low socioeconomic groups: a qualitative study. McCutchan Grace,Wood Fiona,Smits Stephanie,Edwards Adrian,Brain Kate BMC public health BACKGROUND:Socioeconomic inequalities in cancer survival can in part be explained by long patient intervals among people from deprived groups; however, the reasons for this are unclear. This qualitative study explores the actual and anticipated barriers to cancer symptom presentation in the context of socioeconomic deprivation. METHODS:Thirty participants were recruited through the International Cancer Benchmarking Partnership Welsh database (n = 20), snowball sampling (n = 8) and community partners (n = 2). Semi-structured qualitative interviews were conducted with symptomatic and asymptomatic adults over the age of 50 years, who were identified as being from a low socioeconomic group based on multiple individual and group level indicators. Transcripts were analysed using a Framework approach based on the COM-B model (Capability, Opportunity, Motivation-Behaviour). RESULTS:There was evidence of poor awareness of non-specific cancer symptoms (Capability), fearful and fatalistic beliefs about cancer (Motivation), and various barriers to accessing an appointment with the family physician (Opportunity) and full disclosure of symptoms (Capability). These in combination were associated with a lengthened patient interval among participants. Social networks (Opportunity) were influential on the formation of knowledge and beliefs about cancer. Participants' behavioural and normative beliefs were usually formed and reinforced by people they knew with cancer, and such beliefs were considered to lengthen the patient interval. Discussing symptoms with a family member or friend before a visit to the family physician was the norm, and could act as a barrier or facilitator depending on the quality of advice given (Opportunity). Economic hardship meant fulfilling basic day-to-day needs such as finding money for food were prioritised over medical help seeking (Opportunity). CONCLUSIONS:The complex interaction between individual characteristics and socio-environmental factors is important for understanding cancer symptom presentation behaviour, especially in the context of socioeconomic deprivation. Interventions targeted at deprived communities should take into account the wider social influences on symptom presentation behaviour. 10.1186/s12889-016-3733-2
    A self-management support intervention for patients with atrial fibrillation: a randomized controlled pilot trial. Pilot and feasibility studies BACKGROUND:Atrial fibrillation (AF) is the most common arrhythmia worldwide. Despite effective treatment, it is characterized by frequent recurrences. Optimal therapeutic management of AF requires active participation and self-management from patients. Two major components of self-management are self-monitoring and sign-and-symptom management. Pulse self-palpation (PSP) is a method of self-monitoring; however, not all AF patients are capable of successfully performing PSP. Due to a lack of interventions on this topic, a nurse-led intervention for patients with AF (PSPAF intervention) was developed to foster self-monitoring and to enhance self-management through PSP. The purpose of this pilot study was to test the acceptability, feasibility, and potential effects of this intervention on the capability of patients' PSP and sign-and-symptom management. Moreover, we aimed at gathering data on the feasibility of applied research methods to aid in the design of future studies. METHODS:The pilot trial involved 20 adult patients with AF, randomized to an intervention or usual care group. At baseline and during a home visit 3-5 weeks later, we collected data using questionnaires, checklists, field notes, a mobile ECG device, and a diary. Acceptability and feasibility measures were validated through predefined cut-off points. Effect size estimates were expressed as relative risks (RR) and the number needed to treat (NNT). RESULTS:The PSPAF intervention seemed feasible, but only partly acceptable. There were limitations in terms of potential effectiveness, suitability, addressing participants' willingness to implement its content in daily life, and adherence. Estimations of effect sizes suggest a large effect of the intervention on patients' PSP capability (RR = 6.0; 95% CI = [0.83, 43.3]; NNT = 2.4), but almost no effect on sign-and-symptom management (RR = 1.5; 95% CI = [0.7, 3.1]; NNT = 4.0). The feasibility of applied research methods showed minor limitations on recruitment and participant burden. CONCLUSIONS:Despite some limitations, the intervention seemed to be applicable and promising. Taking into account the suggestions and amendments we have made, we recommend conducting a full-scale trial to examine the efficacy of the PSPAF intervention. TRIAL REGISTRATION:This pilot study was registered in the German Clinical Trials Register at September 4, 2017 (Main ID: DRKS00012808). 10.1186/s40814-020-00624-y
    Longitudinal Changes in Symptom Cluster Membership in Inflammatory Bowel Disease. Conley Samantha,Jeon Sangchoon,Proctor Deborah D,Sandler Robert S,Redeker Nancy S Journal of nursing scholarship : an official publication of Sigma Theta Tau International Honor Society of Nursing PURPOSE:To describe changes in symptom cluster membership over 1 year and to examine which demographic and clinical factors predict changes in symptom cluster membership among adults with inflammatory bowel disease. DESIGN:A retrospective longitudinal study of the Crohn's & Colitis Foundation of America Partners Cohort from 2012 to 2015. METHODS:We measured symptoms of pain interference, fatigue, sleep disturbance, depression, and anxiety. We used latent transition analysis to describe changes in symptom cluster membership (baseline, 6 months, and 12 months) and multinomial regressions to examine factors associated with symptom cluster membership transition. FINDINGS:Four groups were identified (N = 5,296): high symptom burden (32.3%-35.3%), low symptom burden (24.2%-27.1%), physical symptoms (19.0%-20.9%; pain, fatigue, sleep disturbance), and psychological symptoms (20.0%-21.5%; depression, anxiety). The probability of staying in the same group was .814 to .905. Moving from active disease into remission was associated with moving from the high burden to low burden and psychological symptom groups. CONCLUSIONS:Symptom cluster membership was quite stable over 1 year. Research is needed to understand the underlying etiology of symptom clusters better and to develop interventions to reduce symptom burden in this vulnerable population. CLINICAL RELEVANCE:Careful consideration of symptom management options should be done with patients to select options that are effective and potentially target multiple symptoms. 10.1111/jnu.12409
    Findings from a pilot randomised trial of a social network self-management intervention in COPD. Welch Lindsay,Orlando Rosanna,Lin Sharon X,Vassilev Ivaylo,Rogers Anne BMC pulmonary medicine BACKGROUND:Self-Management Support (SMS), refers to the actions taken by individuals to recognise and manage their own health. It is increasingly recognised that individuals with chronic obstructive pulmonary disease (COPD) require additional support with their Self-management. Emerging evidence suggests that the use of a social network intervention can improve health outcomes and increase quality of life. In order to understand the potential benefits of SMS in COPD, the GENIE (Generating Engagement in Network Support) SMS tool was implemented and evaluated in a COPD primary care context. The GENIE intervention is a social networking tool that consists of 3 parts; a concentric circle modelling to map existing social networks; a questions sections to elicit preferences for activities; a map of selected resources is then produced, aligned with the user's interests and suggestions for connections to existing network members and to new resources. METHODS:A pilot, parallel, single blind, block randomised controlled trial. Patients with COPD ranging from mild-very severe were recruited. Participants provided written consent and were then randomised to either the intervention or usual care. The primary aim was to understand the clinical benefit through the analysis of health status, symptom burden and quality of life. The secondary outcome measure was health utilisation. NHS cost differences were reported between groups using the GENIE intervention over usual care. RESULTS:The GENIE pilot results demonstrate maintenance in health status and clinical symptoms with a decrease in anxiety. An overall increase in quality of life was observed, these findings did not reach significance. A cost reduction was demonstrated in inpatient stay with no difference in primary care costs. Overall a cost reduction in NHS service utilisation was indicated in the intervention group. CONCLUSION:This pilot study indicated that using a social network intervention can encourage the development of new social connections and extend existing support networks for COPD patients. Increasing network support in this population is of benefit to both patients and NHS providers in terms of cost reductions and enhancing wellbeing. This broadens the understanding of possible new approaches to SMS in community COPD patients, which could now be investigated in a larger population over a longer period. TRIAL REGISTRATION:Clinical Trials.gov PRS National Library of Medicine. Protocol ID number: 19175, Clinical Trial ID: NCT02935452. 10.1186/s12890-020-1130-1
    Validation of brief symptom indexes among patients with recurrent or metastatic squamous cell carcinoma of the head and neck: A trial of the ECOG-ACRIN Cancer Research Group (E1302). Oswald Laura B,Lee Ju-Whei,Argiris Athanassios,Webster Kimberly A,Forastiere Arlene A,Cella David Cancer medicine BACKGROUND:Patients with advanced head and neck cancer have identified pain, fatigue, and difficulties swallowing, breathing, and communicating as high-priority disease-related symptoms. The Functional Assessment of Cancer Therapy-Head and Neck Symptom Index-10 (FHNSI-10) assesses these symptoms. We sought to validate the FHNSI-10, another brief symptom index (FHNSI-7), and individual symptom endpoints representing these high-rated priority disease symptoms among patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). METHODS:Patients (N = 239) were enrolled in a phase III randomized clinical trial (E1302) and completed the FHNSI-10 at multiple time points. We assessed the internal consistencies and test-retest reliabilities of the FHNSI-10 and FHNSI-7 scores, and the known-groups validity, predictive criterion validity, and responsiveness-to-change of the symptom indexes and individual symptom endpoint scores. RESULTS:The FHNSI-10 and FHNSI-7 indexes showed satisfactory internal consistencies (Cronbach's alpha coefficient range 0.60-0.75) and acceptable test-retest reliabilities (intraclass correlation coefficients = 0.75 and 0.74, respectively). The FHNSI-10, FHNSI-7, and the pain, fatigue, swallowing, and breathing symptom scores showed evidence of known-groups validity by performance status at baseline. The FHNSI-10, FHNSI-7, and the pain, fatigue, and breathing symptom scores at baseline showed evidence of predictive criterion validity for overall survival, but not time-to-progression (TTP). Changes in the symptom indexes and individual symptom scores were not associated with changes in performance status over 4 weeks, though most patients had stable performance status. CONCLUSIONS:There is initial evidence of validity for the FHNSI-10 and FHNSI-7 indexes and selected individual symptom endpoints as brief disease-related symptom assessments for patients with recurrent or metastatic SCCHN. 10.1002/cam4.3506
    Clinical decision support system to optimise symptom management in palliative medicine: focus group study. van der Stap Lotte,de Heij Albert H,van der Heide Agnes,Reyners Anna Kl,van der Linden Yvette M BMJ supportive & palliative care OBJECTIVES:Suboptimal symptom control in patients with life-limiting illnesses is a major issue. A clinical decision support system (CDSS) that combines a patient-reported symptom assessment scale (SAS) and guideline-based individualised recommendations has the potential to improve symptom management. However, lacking end-user acceptance often prevents CDSS use in daily practice.We aimed to evaluate the acceptability and feasibility of a palliative care CDSS according to its targeted end-users. METHODS:Six focus groups with different groups of stakeholders were conducted: (1) patient representatives; (2) community nurses; (3) hospital nurses; (4) general practitioners; (5) hospital physicians and (6) palliative care specialists. Audiotapes were transcribed verbatim and thematically analysed. RESULTS:Fifty-one stakeholders (6-12 per focus group) participated. Six themes were discussed: effect, validity, continuity, practical usability, implementation and additional features. All participants expected a CDSS to improve symptom management, for example, by reminding clinicians of blind spots and prompting patient participation. They feared interference with professional autonomy of physicians, doubted the validity of using a patient-reported SAS as CDSS input and thought lacking care continuity would complicate CDSS use. Clinicians needed clear criteria for when to use the CDSS (eg, life-limiting illness, timing in illness trajectory). Participants preferred a patient-coordinated system but were simultaneously concerned patients may be unwilling or unable to fill out an SAS. CONCLUSIONS:A palliative care CDSS was considered useful for improving symptom management. To develop a feasible system, barriers for successful implementation must be addressed including concerns about using a patient-reported SAS, lacking care continuity and unclear indications for use. 10.1136/bmjspcare-2021-002940
    Effects of a self-monitoring intervention in breast cancer patients suffering from taste alterations induced by chemotherapy: A randomized, parallel-group controlled trial. Kinjo Taeko,Kanda Kiyoko,Fujimoto Keiko European journal of oncology nursing : the official journal of European Oncology Nursing Society PURPOSE:This study evaluates the effect of a self-monitoring intervention on taste alterations in breast cancer patients undergoing outpatient chemotherapy. METHODS:The study was a randomized controlled trial. Thirty-four participants were divided into two groups: a self-monitoring (SMG) group (n = 17) and a control group (CG) (n = 17). A conceptual framework was developed with reference to the components of self-management, cognitive behavioral therapy, and the concepts of self-monitoring. Interventions were based on this framework. SMGs recorded their taste symptoms as homework and worked with the researcher to set goals and provide feedback four times every three weeks. In the feedback, the researcher actively listened to the SMG about their feelings and coping strategies during the taste changes, and gave approval and praise for these. The implementation period was 9 weeks for each participant; the CG was provided with conventional nursing support. The intervention was evaluated by comparing the items of symptom improvement, quality of life (QOL), and self-efficacy between the groups before and after the start of the intervention using a scale score. Scale scores were also compared for recognition of taste changes, concerns during treatment, distress, and impacts on each treatment day. RESULTS:SMG had significantly lower scores than CG for perceived change in taste (p = 0.009), and there was an interaction with CG (p = 0.008). SMG had also significantly lower scores than CG in concern during treatment (p = 0.015). CONCLUSION:This study showed that a self-monitoring intervention reduced negative cognition of taste alterations and reduced discomfort. The results suggest that the self-monitoring intervention is effective nursing support for chemotherapy-induced taste alterations. 10.1016/j.ejon.2021.101956
    Symptom response analysis of a randomized controlled trial of reflexology for symptom management among women with advanced breast cancer. Sikorskii Alla,Niyogi Pratim Guha,Victorson David,Tamkus Deimante,Wyatt Gwen Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:To examine symptom responses resulting from a home-based reflexology intervention delivered by a friend/family caregivers to women with advanced breast cancer undergoing chemotherapy, targeted, and/or hormonal therapy. METHODS:Patient-caregiver dyads (N = 256) were randomized to 4 weekly reflexology sessions or attention control. Caregivers in the intervention group were trained by a reflexology practitioner in a 30-min protocol. During the 4 weeks, both groups completed telephone symptom assessments using the M. D. Anderson Symptom Inventory. Those who completed at least one weekly call were included in this secondary analysis (N = 209). Each symptom was categorized as mild, moderate, or severe using established interference-based cut-points. Symptom response meant an improvement by at least one category or remaining mild. Symptom responses were treated as multiple events within patients and analyzed using generalized estimating equations technique. RESULTS:Reflexology was more successful than attention control in producing responses for pain (OR = 1.84, 95% CI (1.05, 3.23), p = 0.03), with no significant differences for other symptoms. In the reflexology group, greater probability of response across all symptoms was associated with lower number of comorbid condition and lower depressive symptomatology at baseline. Compared to odds of responses on pain (chosen as a referent symptom), greater odds of symptom response were found for disturbed sleep and difficulty remembering with older aged participants. CONCLUSIONS:Home-based caregiver-delivered reflexology was helpful in decreasing patient-reported pain. Age, comorbid conditions, and depression are potentially important tailoring factors for future research and can be used to identify patients who may benefit from reflexology. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT01582971. 10.1007/s00520-019-04959-y
    Perspectives of Patients, Nurses, and Nephrologists About Electronic Symptom Monitoring With Feedback in Hemodialysis Care. American journal of kidney diseases : the official journal of the National Kidney Foundation RATIONALE & OBJECTIVE:Patients receiving hemodialysis experience high symptom burden and low quality of life (QOL). Electronic patient-reported outcome measures (e-PROMs) monitoring with feedback to clinicians may be an acceptable intervention to improve health-related QOL for patients receiving hemodialysis. This study explored patient and clinician perspectives on e-PROMs monitoring with feedback to clinicians. STUDY DESIGN:Qualitative study. SETTING & PARTICIPANTS:41 participants (12 patients, 13 nephrologists, 16 dialysis nurses) who participated in a 6-month feasibility pilot study of adults receiving facility-based hemodialysis across 4 Australian units. The intervention consisted of electronic symptom monitoring with feedback to clinicians, who also received evidence-based symptom management recommendations to improve health-related QOL. ANALYTICAL APPROACH:Semistructured interviews and focus group discussions explored the feasibility and acceptability of e-PROMs monitoring with feedback to clinicians. We conducted a thematic analysis of transcripts. RESULTS:We identified 4 themes: enabling efficient, systematic, and multidisciplinary patient-centered care; experiencing limited data and options for symptom management; requiring familiarity with technology and processes; and identifying barriers and competing priorities. While insufficient patient engagement, logistic/technical challenges, and delayed symptom feedback emerged as barriers to implementation, active engagement by nurses in encouraging and supporting patients during survey completion and clinicians' prompt action after symptom feedback were considered to be facilitators to implementation. LIMITATIONS:Limited generalizability due to inclusion of English-speaking participants only. CONCLUSIONS:Patients, nurses, and nephrologists considered e-PROMs monitoring with feedback to clinicians feasible for symptom management in hemodialysis. Clinician engagement, patient support, reliable technology, timely symptom feedback, and interventions to address symptom burden are likely to improve its implementation within research and clinical settings. 10.1053/j.ajkd.2021.12.007
    Mobile App for Symptom Management and Associated Quality of Life During Systemic Treatment in Early Stage Breast Cancer: Nonrandomized Controlled Prospective Cohort Study. Grašič Kuhar Cvetka,Gortnar Cepeda Tjaša,Kovač Timotej,Kukar Matjaž,Ružić Gorenjec Nina JMIR mHealth and uHealth BACKGROUND:Providing patients with cancer who are undergoing systemic therapy with useful information about symptom management is essential to prevent unnecessary deterioration of quality of life. OBJECTIVE:The aim was to evaluate whether use of an app for symptom management was associated with any change in patient quality of life or use of health resources. METHODS:Outpatients with early stage breast cancer receiving systemic therapy were recruited at the Institute of Oncology in Ljubljana, Slovenia. Patients who received systemic therapy between December 2017 and March 2018 (control group) and between April 2018 and September 2018 (intervention group) were eligible. All patients received standard care, but only those in the intervention group were asked to use mPRO Mamma, an Android-based smartphone app, in addition. The app supported daily tracking of 50 symptoms, allowed users to grade their symptom severity (as mild, moderate, or severe), and also provided in-depth descriptions and recommendations based on reported symptom level. Patient-reported outcomes in both groups were assessed through the European Organisation for Research and Treatment of Cancer (EORTC) core (C-30) and breast cancer (BR-23) questionnaires, as well as a questionnaire about health resources use. The primary outcomes were the difference in the global quality of life between groups and the difference in summary score of the EORTC C-30 questionnaire between groups after 3 time periods (the first week of treatment, the first treatment cycle, and the entire treatment). The secondary outcome was the use of health resources (doctor visits and hospitalizations) in each time period. Other scales were used for exploratory analysis. RESULTS:The mean difference between the intervention group (n=46) and the control group (n=45) in global quality of life (adjusted for baseline and type of surgery) after the first week was 10.1 (95% CI 1.8 to 18.5, P=.02). The intervention group summary scores were significantly higher than those of the control group after the first week (adjusted mean difference: 8.9, 95% CI 3.1 to 14.7, P=.003) and at the end of treatment (adjusted mean difference: 10.6, 95% CI 3.9 to 17.3, P=.002). Use of health resources was not statistically significant between the groups in either the first week (P=.12) or the first treatment cycle (P=.13). Exploratory analysis findings demonstrated clinically important improvements (indicated by EORTC C-30 or BR-23 scale scores)-social, physical, role, and cognitive function were improved while pain, appetite loss, and systemic therapy side effects were reduced. CONCLUSIONS:Use of the app enabled patients undergoing systemic therapy for early stage breast cancer to better cope with symptoms which was demonstrated by a better global quality of life and summary score after the first week and by a better summary score at the end of treatment in the intervention group compared to those of the control group, but no change in the use of health resources was demonstrated. 10.2196/17408
    Decreased symptom burden following surgery due to support from an interactive app for symptom management for patients with pancreatic and periampullary cancer. Gustavell Tina,Sundberg Kay,Segersvärd Ralf,Wengström Yvonne,Langius-Eklöf Ann Acta oncologica (Stockholm, Sweden) Patients with pancreatic and periampullary cancer have poor prognoses, experience multiple symptoms following surgery and sometimes lack knowledge of self-care activities. Consequently, it is vital to develop systems that support self-management, improvement of health-related quality of life and reduction of symptoms. Therefore, the aim was to evaluate the impact on health-related quality of life and self-care activity when using the Interaktor app following pancreaticoduodenectomy due to cancer. Patients in the intervention group used Interaktor up to six months after surgery. They reported symptoms daily at home and received support for self-management by continuous access to written self-care advice and to their healthcare professionals. Descriptive data from the app were collected. Health-related quality of life and self-care activity were collected before surgery, and six weeks and six months after surgery. Comparisons between the intervention group ( = 26) and a historical control group ( = 33) were made. Decline/dropout rate was 37% in the intervention group and 10% in the control group. Six weeks after surgery the intervention group rated significantly higher emotional functioning and less nausea/vomiting, pain, appetite loss, constipation, pancreatic pain, flatulence and worry about low weight. Twenty-five subscales/items showed non-statistical differences. Six months after surgery the intervention group rated significantly fewer hepatic symptoms, less worry about low weight, and higher self-care activity level. Thirty subscales/items showed non-statistical differences. The first four weeks, patients reported symptoms in a median 95% of the intended days, and for the rest of the period in median 83%. The use of an app for management of patient-reported outcomes reduces symptom burdens six weeks after pancreaticoduodenectomy due to cancer. Interaktor is well accepted for patients choosing to participate and appears to facilitate supportive care needs and timely symptom management for this patient group. Future studies should also include cost-benefits and objective measures. 10.1080/0284186X.2019.1633473
    Implementation of the Symptom Navi © Programme for cancer patients in the Swiss outpatient setting: a study protocol for a cluster randomised pilot study (Symptom Navi© Pilot Study). Bana Marika,Ribi Karin,Kropf-Staub Susanne,Zürcher-Florin Sabin,Näf Ernst,Manser Tanja,Bütikofer Lukas,Rintelen Felix,Peters Solange,Eicher Manuela BMJ open INTRODUCTION:Self-management interventions show promising results on symptom outcomes and self-management behaviours. The Symptom Navi© Programme (SN©P) is a nurse-led intervention supporting patients' symptom self-management during anticancer treatment. It consists of written patient information (Symptom Navi© Flyers (SN©Flyers)), semistructured consultations and a training manual for nurses. METHODS AND ANALYSIS:This pilot study will evaluate the implementation of the SN©P based on the Reach Effectiveness-Adoption Implementation Maintenance framework at Swiss outpatient cancer centres. We will use a cluster-randomised design and randomise the nine participating centres to the intervention or usual care group. We expect to include 140 adult cancer patients receiving first-line systemic anticancer treatment. Trained nurses at the intervention clusters will provide at least two semistructured consultations with the involvement of SN©Flyers. Outcomes include patients' accrual and retention rates, patient-reported interference of symptoms with daily functions, symptom burden, perceived self-efficacy, quality of nursing care, nurse-reported facilitators and barriers of adopting the programme, nurses' fidelity of providing the intervention as intended, and patients' safety (patients timely reporting of severe symptoms). We will use validated questionnaires for patient-reported outcomes, focus group interviews with nurses and individual interviews with oncologists. Linear mixed models will be used to analyse patient-reported outcomes. Focus group and individual interviews will be analysed by thematic analysis. ETHICS AND DISSEMINATION:The Symptom Navi© Pilot Study has been reviewed and approved by Swiss Ethic Committee Bern (KEK-BE: 2017-00020). Results of the study will be disseminated in peer-reviewed journal and at scientific conferences. TRIAL REGISTRATION NUMBER:NCT03649984; Pre-results. 10.1136/bmjopen-2018-027942
    Acceptance and Commitment Therapy for Symptom Interference in Advanced Lung Cancer and Caregiver Distress: A Pilot Randomized Trial. Mosher Catherine E,Secinti Ekin,Hirsh Adam T,Hanna Nasser,Einhorn Lawrence H,Jalal Shadia I,Durm Gregory,Champion Victoria L,Johns Shelley A Journal of pain and symptom management CONTEXT:Advanced lung cancer patients typically have a poor prognosis and many symptoms that interfere with functioning, contributing to high rates of emotional distress in both patients and family caregivers. There remains a need for evidence-based interventions to improve functional outcomes and distress in this population. OBJECTIVES:This pilot trial examined the feasibility and preliminary efficacy of telephone-based Acceptance and Commitment Therapy (ACT) for symptomatic, advanced lung cancer patients and their distressed family caregivers. Primary outcomes were patient symptom interference with functioning and patient and caregiver distress. METHODS:Symptomatic, advanced lung cancer patients and distressed caregivers (n = 50 dyads) were randomly assigned to six sessions of ACT or an education/support condition. Patients completed measures of symptom interference and measures assessing the severity of fatigue, pain, sleep disturbance, and breathlessness. Patients and caregivers completed measures of distress and illness acceptance and struggle. RESULTS:The eligibility screening rate (51%) and retention rate (76% at six weeks postintervention) demonstrated feasibility. No group differences were found with respect to patient and caregiver outcomes. Both groups showed a small, significant decrease in struggle with the illness over the study period, but did not show meaningful change in other outcomes. CONCLUSION:Findings suggest that telephone-based ACT is feasible for many advanced lung cancer patients and caregivers, but may not substantially reduce symptom interference and distress. Low baseline levels of certain symptoms may have contributed to null findings. Next steps include applying ACT to specific, clinically meaningful symptom interference and varying intervention dose and modality. 10.1016/j.jpainsymman.2019.06.021
    A pilot study of the effect of a home-based multimodal symptom-management program in children and adolescents undergoing chemotherapy. Cheng Karis Kin-Fong,Tan Laura Mei Lian Cancer reports (Hoboken, N.J.) BACKGROUND:Prevalent symptoms that affect children and adolescents throughout the process of cancer diagnosis and treatment include nausea and vomiting, fatigue, pain, mucositis, and anxiety. AIM:To examine the effect of a home-based multimodal symptom-management program for alleviation of nausea and vomiting, fatigue, pain, mucositis, and anxiety in children and adolescents undergoing chemotherapy for hematological malignancies or solid tumors. METHODS:In an exploratory pilot randomized study with qualitative interview, patients between 10 and 18 years of age were randomly assigned to either the symptom-management program plus usual care (intervention group) or usual care (control group). The program consisted of multiple nonpharmacological interventional components. The targeted symptoms were measured at baseline (after diagnosis), at the first 2 weeks of each cycle of chemotherapy, and at 6 months after baseline, using the Memorial Symptom Assessment Scale 10-18 and the State Anxiety Scale for Children. RESULTS:Fifty children (31 boys; mean age, 13.7 years) were randomized either to the intervention group or the control group (25 each) and underwent baseline assessment. A comparison between the groups showed that the intervention group had a significant less fatigue over time (P < .05). However, no differences were found with respect to nausea and vomiting, pain, mucositis, and anxiety between groups. Both children and parents reported a positive experience with the symptom-management program. CONCLUSION:The home-based symptom-management program may have helped to reduce fatigue in children and adolescents undergoing chemotherapy. In addition, qualitative data support the importance of improving children and parents' knowledge, coping skills, and psychological preparation for symptoms associated with chemotherapy. 10.1002/cnr2.1336
    Clinical Decision Support for Symptom Management in Lung Cancer Patients: A Group RCT. Journal of pain and symptom management CONTEXT:Clinical guidelines are available to enhance symptom management during cancer treatment but often are not used in the practice setting. Clinical decision support can facilitate the implementation and adherence to clinical guidelines. and improve the quality of cancer care. OBJECTIVES:Clinical decision support offers an innovative approach to integrate guideline-based symptom management into oncology care. This study evaluated the effect of clinical decision support-based recommendations on clinical management of symptoms and health-related quality of life (HR-QOL) among outpatients with lung cancer. METHODS:Twenty providers and 179 patients were allotted in group randomization to attention control (AC) or Symptom Assessment and Management Intervention (SAMI) arms. SAMI entailed patient-report of symptoms and delivery of recommendations to manage pain, fatigue, dyspnea, depression, and anxiety; AC entailed symptom reporting prior to the visit. Outcomes were collected at baseline, two, four and six-months. Adherence to recommendations was assessed through masked chart review. HR-QOL was measured by the Functional Assessment of Cancer Therapy-Lung questionnaire. Descriptive statistics with linear and logistic regression accounting for the clustering structure of the design and a modified chi-square test were used for analyses. RESULTS:Median age of patients was 63 years, 58% female, 88% white, and 32% ≤high school education. Significant differences in clinical management were evident in SAMI vs. AC for all target symptoms that passed threshold. Patients in SAMI were more likely to receive sustained-release opioids for constant pain, adjuvant medications for neuropathic pain, opioids for dyspnea, stimulants for fatigue and mental health referrals for anxiety. However, there were no statistically significant differences in HR-QOL at any time point. CONCLUSION:SAMI improved clinical management for all target symptoms but did not improve patient outcomes. A larger study is warranted to evaluate effectiveness. 10.1016/j.jpainsymman.2021.12.006
    An Educational and Skill-Building Intervention to Improve Symptom Recognition and Interpretation in Women With Acute Coronary Syndrome: A Pilot Study. Davis Leslie L,McCoy Thomas P Dimensions of critical care nursing : DCCN BACKGROUND:The type of symptoms that a woman experiences during an acute coronary syndrome (ACS) event influences symptom recognition and interpretation. Women who experience intense, abrupt symptoms are more likely to correctly attribute symptoms to a cardiac etiology and seek care faster than women with less intense, intermittent symptoms. OBJECTIVE:A single-group pretest-posttest design was used to evaluate the feasibility and acceptability of a nurse-delivered education and skill-building intervention designed to improve symptom recognition and interpretation in women with recurrent ACS symptoms. METHODS:Women hospitalized for an ACS event received an individualized education and skill-building intervention that was conceptually framed by the investigator's previous research. Three in-person sessions were followed by 2 telephone sessions for reinforcement. Outcomes and acceptability were evaluated at close-out (approximately 2 months after the index event). RESULTS:All but 2 women approached agreed to participate. Of the 10 women enrolled, 9 completed all study sessions within an average of 55 days. Mean knowledge scores increased by 7.4% measured by the ACS Response Index. Attitudes toward symptom recognition and help seeking increased by 2.4, whereas beliefs toward expectations and actions increased by 3.2. The women were pleased with the intervention (satisfaction scores averaging 1.4 on a 4-point Likert scale, with 1 as "strongly agree" and 4 as "strongly disagree"). All women who completed the study would recommend it to others. CONCLUSION:The nurse-delivered intervention was feasible and acceptable to women in the study. Results support further testing and refinement of the intervention in a longitudinal randomized control study to determine efficacy and sustainability. 10.1097/DCC.0000000000000329
    Impact of Pre-Chemotherapy Education with Audio Visual Methods on the Self-Efficacy of Symptom Management in Patients with Cancer. Mumtaz Dzakiyatul Fahmi,Effendy Christantie,Haryani Haryani Journal of cancer education : the official journal of the American Association for Cancer Education This study aimed to identify the effects of pre-chemotherapy education with audio visual methods on the self-efficacy of symptom management in patients with cancer who received chemotherapy. The various side effects of chemotherapy could affect the self-efficacy of symptom management. Providing pre-chemotherapy education is important to improve the self-efficacy of symptom management. Nowadays, pre-chemotherapy education is only given by using print media, which can restrict transferring information to patients with cancer. This study was based on pre- and post-test, 2 group, quasi-experimental design. A total of 80 respondents were recruited with consecutive sampling between January and March 2019. Participants in the intervention group received video pre-chemotherapy education, while participants in the control group received education with a booklet (usual care). Patients completed self-efficacy symptom management questionnaires before and 1-2 weeks after chemotherapy. The analysis used the Wilcoxon and Mann-Whitney tests and by counting Cohen's d effect size. The mean scores of pre- and post-test self-efficacy of symptom management increased in the intervention group to 1.77 (p = 0.000) and in the control group to 0.64 (p = 0.001). The comparative test between the two groups showed p = 0.005 (p < 0.05) with an effect size of 0.4 (66%). This result indicates that pre-chemotherapy education had medium effect on the self-efficacy of symptom management. Pre-chemotherapy education with audio visual methods can increase the self-efficacy of symptom management in patients with cancer. 10.1007/s13187-021-02006-1
    Nursing intervention to enhance outpatient chemotherapy symptom management: Patient-reported outcomes of a randomized controlled trial. Traeger Lara,McDonnell Theresa M,McCarty Caitlin E,Greer Joseph A,El-Jawahri Areej,Temel Jennifer S Cancer BACKGROUND:The authors conducted a randomized controlled trial to evaluate a nurse practitioner (NP)-delivered symptom management intervention for patients initiating chemotherapy for nonmetastatic cancer. The aim was to reduce patient-reported symptom burden by facilitating patient-NP collaboration and the early management of symptoms. METHODS:At the time of the first chemotherapy visit, adult participants with nonmetastatic breast, colorectal, or lung cancer (120 participants) completed self-report measures and were then randomly assigned to standard care plus the intervention or standard care alone. Intervention participants received proactive telephone calls from their oncology team NP during the week after each of the first 2 chemotherapy administration visits. Measures were repeated at the second and third chemotherapy visits. Group differences were analyzed with regard to patient-reported symptoms (Memorial Symptom Assessment Scale-Short Form items), satisfaction with care (Family Caregiver Satisfaction-patient scale), and the likelihood of depression or anxiety symptoms (Patient Health Questionnaire-4). RESULTS:At the time of the first visit, 50.8% of participants reported ≥1 physical symptom, most commonly lack of energy (35.8%) and drowsiness (30.8%). The number of symptoms (gamma coefficient [γ] = 0.16; P<.001), symptom distress (γ = 0.45; P<.001), and satisfaction with care (γ = 0.24; P = .004) increased whereas the likelihood of anxiety symptoms decreased (γ = -0.19; P = .02) and the likelihood of depression symptoms did not change (γ = 0.01; P = .91). Outcomes did not differ by randomized group. Randomized group interacted with emetogenic potential in predicting symptom distress (γ = 0.43; P = .03) and satisfaction with care (γ = -0.45; P = .045). CONCLUSIONS:The intervention did not appear to reduce symptom burden compared with standard care. Early symptoms highlight the importance of continuing to examine strategies to improve symptom management during chemotherapy for nonmetastatic disease. 10.1002/cncr.29585
    Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: A Multicenter Randomized Controlled Trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:We aimed to evaluate the efficacy and feasibility of patient-reported outcome (PRO)-based symptom management in the early period after lung cancer surgery. METHODS:Before surgery, patients with clinically diagnosed lung cancer were randomly assigned 1:1 to receive postoperative PRO-based symptom management or usual care. All patients reported symptoms on MD Anderson Symptom Inventory-Lung Cancer presurgery, daily postsurgery, and twice a week after discharge for up to 4 weeks via an electronic PRO system. In the intervention group, treating surgeons responded to overthreshold electronic alerts driven by any of the five target symptom scores (score ≥ 4 on a 0-10 scale for pain, fatigue, disturbed sleep, shortness of breath, and coughing). The control group patients received usual care and no alerts were generated. The primary outcome was the number of symptom threshold events (any target symptom with a score of ≥ 4) at discharge. Per-protocol analyses were conducted. RESULTS:Of the 166 participants, 83 were randomly allocated to each group. At discharge, the intervention group reported fewer symptom threshold events than the control group (median [interquartile range], 0 [0-2] 2 [0-3]; = .007). At 4 weeks postdischarge, this difference was maintained between the intervention and control groups (median [interquartile range], 0 [0-0] 0 [0-1]; = .018). The intervention group had a lower complication rate than the control group (21.5% 40.6%; = .019). Surgeons spent a median of 3 minutes managing an alert. CONCLUSION:PRO-based symptom management after lung cancer surgery showed lower symptom burden and fewer complications than usual care for up to 4 weeks postdischarge. 10.1200/JCO.21.01344
    Temporal relationship of posttraumatic stress disorder symptom clusters during and after an expressive writing intervention for Chinese American breast cancer survivors. Chu Qiao,Wu Ivan Haw Chong,Tang Moni,Tsoh Janice,Lu Qian Journal of psychosomatic research OBJECTIVE:Posttraumatic stress disorder (PTSD) is a significant condition and frequently observed among breast cancer survivors. Extant literature has demonstrated the effectiveness of expressive writing interventions in reducing PTSD among breast cancer survivors. However, little is known about how different PTSD symptom clusters influence each other over time during and after the expressive writing intervention among breast cancer survivors. We investigated how the three PTSD symptom clusters (reexperiencing, avoidance and hyperarousal) influence each other during and after an expressive writing intervention among Chinese American breast cancer survivors. METHODS:Chinese American breast cancer survivors (n = 136) completed an expressive writing intervention. Their PTSD symptoms were assessed at baseline, 1-, 3-, and 6-month follow-ups. RESULTS:Using cross-lagged panel analysis, the model with hyperarousal symptoms at each assessment wave predicting the subsequent severity of avoidance and reexperiencing symptoms indicated the best fit, χ(52) = 65.422, p = .100; CFI = 0.990, RMSEA = 0.044, 95% CI [0.000, 0.074]. CONCLUSION:The results suggest that hyperarousal symptoms predict the subsequent severity of reexperiencing and avoidance symptoms over time during and after the expressive writing intervention. The findings highlight the importance of early diagnosis, monitoring and treatment of hyperarousal symptoms in enhancing the efficacy of PTSD interventions and reducing the chronicity in PTSD among Chinese American breast cancer survivors. Clinical Trial Registration atClinicalTrials.gov: NCT02946619. 10.1016/j.jpsychores.2020.110142
    Symptom Management Among Cancer Survivors: Randomized Pilot Intervention Trial of Heart Rate Variability Biofeedback. Burch James B,Ginsberg J P,McLain Alexander C,Franco Regina,Stokes Sherry,Susko Kerri,Hendry William,Crowley Elizabeth,Christ Alex,Hanna John,Anderson Annie,Hébert James R,O'Rourke Mark A Applied psychophysiology and biofeedback Chronic cancer-related symptoms (stress, fatigue, pain, depression, insomnia) may be linked with sympathetic nervous system over-activation and autonomic imbalance. Decreased heart rate variability (HRV) is an indicator of autonomic dysregulation that is commonly observed among cancer survivors. HRV biofeedback (HRVB) training induces HRV coherence, which maximizes HRV and facilitates autonomic and cardiorespiratory homeostasis. This randomized, wait-list-controlled, pilot intervention trial tested the hypothesis that HRVB can improve HRV coherence and alleviate cancer-related symptoms. The intervention group (n = 17) received 4-6 weekly HRVB training sessions until participants demonstrated skill acquisition. Controls (n = 17) received usual care. Outcomes assessed at baseline and follow-up included 15-min HRV recordings (HRV Coherence Ratio), and symptoms of: stress, distress, post-traumatic stress disorder (PTSD), pain, depression, fatigue, and sleep disturbance. Linear mixed models for repeated measures were used to assess Group-by-Time interactions, pre- versus post-treatment differences in mean symptom scores, and group differences at follow-up. Mean HRV Coherence Ratios (± standard error) improved in the HRVB group at follow-up (baseline: 0.37 ± 0.05, post-intervention: 0.84 ± 0.18, p = 0.01), indicating intervention validity. Statistically significant Group-by-Time interactions indicated treatment-related improvements in HRV Coherence Ratios (p = 0.03, Pre-vs. post-treatment effect size [Cohen's d]: 0.98), sleep symptoms (p = 0.001, d = 1.19), and sleep-related daytime impairment (p = 0.005, d = 0.86). Relative to controls, the intervention group experienced trends toward improvements in stress, distress, fatigue, PTSD, and depression, although no other statistically significant Group-by-Time interactions were observed. This pilot intervention found that HRVB training reduced symptoms of sleep disturbance among cancer survivors. Larger-scale interventions are warranted to further evaluate the role of HRVB for managing symptoms in this population. Registration: NCT03692624 www.clinicaltrials.gov. 10.1007/s10484-020-09462-3
    Testing Symptom Severity Thresholds and Potential Alerts for Clinical Intervention in Patients With Cancer Undergoing Chemotherapy. Shi Qiuling,Lee Ju-Whei,Wang Xin Shelley,Fisch Michael J,Chang Victor T,Wagner Lynne,Cleeland Charles S JCO oncology practice PURPOSE:Symptom monitoring is attracting attention as a way to improve adherence to cancer therapy, reduce treatment-related toxicities, and possibly improve overall survival. How reporting thresholds affect symptom alert generation and clinical outcomes is poorly understood. PATIENTS AND METHODS:We analyzed data from 38 US health care institutions collected for the prospective Eastern Cooperative Oncology Group-American College of Radiology Imaging Network E2Z02 Symptom Outcomes and Practice Patterns study. Participants were outpatients receiving chemotherapy for breast (n = 642), colorectal (n = 486), or lung cancer (n = 340) who rated symptom severity using the MD Anderson Symptom Inventory at 2 assessment points 1 month apart. Percentages of patients with pain, dyspnea, fatigue, or distress at different thresholds (score of 4-7 on a 0-10 scale) were compared. The percentage of patients whose performance status had worsened at follow-up was used to estimate risk for missing clinically important symptom data by using higher severity thresholds. RESULTS:At the guideline-recommended threshold of ≥ 4, suprathreshold rates were 60% for any of the 4 symptoms at the initial survey; performance status worsened at follow-up for 27% of all patients with any symptom rated ≥ 4 at the initiate survey. When the threshold was increased to ≥ 7, approximately half of patients (51%) with worsened performance status were not identified. CONCLUSION:The burden to clinicians from an alert threshold of ≥ 4 (per many current guidelines) would be substantial. However, setting higher alert thresholds may miss a large percentage of patients who need clinical intervention. These results may inform resource planning when implementing electronic symptom screening at an institutional or practice level. 10.1200/JOP.19.00403
    Emotion And Symptom-focused Engagement (EASE): a randomized phase II trial of an integrated psychological and palliative care intervention for patients with acute leukemia. Rodin Gary,Malfitano Carmine,Rydall Anne,Schimmer Aaron,Marmar Charles M,Mah Kenneth,Lo Christopher,Nissim Rinat,Zimmermann Camilla Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:We designed a novel, manualized intervention called Emotion And Symptom-focused Engagement (EASE) for acute leukemia (AL) and report here on a phase II randomized controlled trial (RCT) to assess its feasibility and preliminary efficacy. METHODS:Patients were recruited within 1 month of hospital admission and randomized to EASE plus usual care (UC) or UC alone. EASE includes (1) EASE-psy, a tailored psychotherapy delivered over 8 weeks, and (2) EASE-phys, weekly physical symptom screening over 8 weeks to trigger early palliative care. The primary outcome was traumatic stress symptoms; secondary outcomes included physical symptom burden and quality of life. Assessments were conducted at baseline and at 4, 8, and 12 weeks. Between-group differences were evaluated using multilevel modeling. RESULTS:Forty-two patients were randomized to EASE (n = 22) or UC (n = 20), with 76% retention at 12 weeks. Predefined feasibility outcomes were met: 86% (19/22) of EASE participants completed ≥ 50% of EASE-psy sessions (goal ≥ 64%); 100% received Edmonton Symptom Assessment System (ESAS, modified for AL) screenings, 64% (14/22) of whom completed ≥ 50% of planned screenings (goal ≥50%); and 100% with scores ≥ 4/10 on any physical ESAS-AL item had ≥ 1 meeting with the EASE-phys team (goal 100%). Significant treatment-group differences favoring EASE were observed in traumatic stress symptoms at 4 and 12 weeks, and pain intensity and interference at 12 weeks (all p < .05). CONCLUSIONS:EASE is feasible in patients newly diagnosed with AL and shows promise of effectiveness. These results warrant a larger RCT to provide evidence for its more routine use as a standard of care. 10.1007/s00520-019-04723-2
    SYMPERHEART: an intervention to support symptom perception in persons with heart failure and their informal caregiver: a feasibility quasi-experimental study protocol. Santos Gabrielle Cécile,Liljeroos Maria,Hullin Roger,Denhaerynck Kris,Wicht Justine,Jurgens Corrine Y,Schäfer-Keller Petra BMJ open INTRODUCTION:Symptom perception in heart failure (HF) has been identified as crucial for effective self-care, and is related to patient and health system outcomes. There is uncertainty regarding the feasibility and acceptability of symptom perception support and doubts regarding how to include informal caregivers. This study aims to test the feasibility, acceptability and outcome responsiveness of an intervention supporting symptom perception in persons with HF and their informal caregiver. METHODS AND ANALYSIS:A feasibility study with a quasi-experimental pretest and post-test single group design is conducted. The convenience sample consists of 30 persons with HF, their informal caregivers and six nurses. SYMPERHEART is an evidence-informed intervention that targets symptom perception by educational and support components. Feasibility is measured by time-to-recruit; time-to-deliver; eligibility rate; intervention delivery fidelity rate. Acceptability is measured by rate of consent, retention rate, treatment acceptability and the engagement in the intervention components. Outcome responsiveness includes: HF self-care (via the Self-care of Heart Failure Index V.7.2); perception of HF symptom burden (via the Heart Failure Somatic Perception Scale V.3); health status (via the Kansas City Cardiomyopathy Questionnaire-12); caregivers' contribution to HF self-care (via the Caregiver Contribution to Self-Care of Heart Failure Index 2); caregivers' burden (via the Zarit Burden Interview). Clinical outcomes include HF events, hospitalisation reason and length of hospital stay. Descriptive statistics will be used to report feasibility, acceptability, patient-reported outcomes (PRO) and clinical outcomes. PRO and caregiver-reported outcome responsiveness will be reported with mean absolute change and effect sizes. ETHICS AND DISSEMINATION:The study is conducted according to the Declaration of Helsinki. The Human Research Ethics Committee of the Canton of Vaud, Switzerland, has approved the study. Written informed consent from persons with HF and informal caregivers are obtained. Results will be published via peer reviewed and professional journals, and further disseminated via congresses. TRIAL REGISTRATION NUMBER:ISRCTN18151041. 10.1136/bmjopen-2021-052208
    Randomized controlled trial of a brief cognitive-behavioral strategies intervention for the pain, fatigue, and sleep disturbance symptom cluster in advanced cancer. Kwekkeboom Kristine,Zhang Yingzi,Campbell Toby,Coe Christopher L,Costanzo Erin,Serlin Ronald C,Ward Sandra Psycho-oncology OBJECTIVE:Patients receiving treatment for advanced cancer suffer significant symptom burden, including co-occurring pain, fatigue, and sleep disturbance. There is limited evidence for effective interventions targeting this common symptom cluster. METHODS:A randomized controlled trial of a brief cognitive-behavioral strategies (CBS) intervention was conducted. A sample of 164 patients with advanced cancer receiving chemotherapy practiced imagery, relaxation, and distraction exercises or listened to cancer education recordings (attention-control) to manage co-occurring pain, fatigue, and sleep disturbance over a 9-week period. Symptom cluster severity, distress, and interference with daily life were measured at baseline and 3, 6, and 9 weeks. We also evaluated the moderating influence of imaging ability and number of concurrent symptoms, and mediating effects of changes in stress, anxiety, outcome expectancy, and perceived control over symptoms. RESULTS:Compared with the cancer education condition, participants receiving the CBS intervention reported less symptom cluster distress at week 6 (M = 1.82 vs 2.15 on a 0-4 scale, P < .05). No other group differences were statistically significant. The number of concurrent symptoms moderated the intervention effect on symptom cluster interference. Changes in stress, outcome expectancy, and perceived control mediated the extent of intervention effects on symptom outcomes, primarily at weeks 6 and 9. CONCLUSIONS:The brief CBS intervention had limited effects in this trial. However, findings regarding potential mediators affirm hypothesized mechanisms and provide insight into ways to strengthen future interventions to reduce the suffering associated with co-occurring pain, fatigue, and sleep disturbance. 10.1002/pon.4883
    Effects of a group-based physical activity program for pediatric patients with cancer on physical activity and symptom experience: A quasi-experimental study. Ouyang Na,Cai Ruiqing,Zhou Xuezhen,Huang Haiying,Qiu Xing,Liu Ke Pediatric blood & cancer AIMS:To examine the effects of a group-based physical activity intervention on improvement in physical activity and mitigation of symptom distress among pediatric patients with cancer. METHODS:Based on convenience sampling, 57 pediatric patients with cancer admitted to the cancer center were included in the intervention group. The control group included 57 pediatric patients with cancer from two other hospitals matched to the patients in the intervention group by age, sex, and diagnosis. A group-based physical activity program was implemented among the children in the intervention group, whereas the children in the control group received standard care. Physical activity and symptoms were measured using the Children's Leisure Time Activities Study Survey-Chinese and using the Memorial Symptom Assessment Scale 10-18 at baseline and after the 12 exercise session in both the intervention and control groups. RESULTS:The repeated-measures analysis of variance showed that the main intervention effects on the decrease in light-intensity physical activity and increase in moderate-to-vigorous physical activity were significant between the two groups (P < .001). The group-based physical activity intervention could decrease the scores of psychological symptoms (P < .001), Global Distress Index (P < .001), and physical symptoms (P = .01) when comparing the difference between the two groups before and after the intervention. There was no significant difference in the number of symptoms or the total symptom experience score between the two groups. CONCLUSION:These findings suggest that a group-based physical activity intervention can promote physical activity and relieve psychological and physical symptom distress among pediatric patients with cancer. 10.1002/pbc.27965
    Managing the nutrition impact symptom cluster in patients with nasopharyngeal carcinoma using an educational intervention program: A pilot study. Xiao Wenli,Chan Carmen Wh,Jinnan Xiao,Lyu Qiyuan,Gong Ni,Wong Cho Lee,Chow Ka Ming European journal of oncology nursing : the official journal of European Oncology Nursing Society PURPOSE:This study aimed to test the feasibility and estimate the effectiveness of a theory-driven and evidence-based educational intervention program to manage the nutrition impact symptom cluster in patients undergoing radiotherapy for nasopharyngeal carcinoma (NPC). METHODS:A pilot randomized controlled trial was performed. Forty patients were divided equally into the intervention and control groups. The patients in the intervention group attended 2 face-to-face individual instructional sessions to enhance their knowledge and skills in managing the cluster. The study outcomes were the severity of the nutrition impact symptom cluster, body weight, symptom interference, and quality of life (QOL). A generalized estimating equation model was used to compare the differences in the outcome variables between the groups over 3-time points. RESULTS:The consent rate for the study was 95.2%, and the attrition rate was 5.0%. Although no significant differences between the groups were detected from T1 to T3, favorable effects on relieving the cluster itself (B [95% confidence interval (CI)] = -0.844 [-2.261, 0.572], p = 0.243, Cohen's d [95% CI] = -0.37 [-1.00, 0.28]) and improvements in physical well-being (B [95% CI] = 0.833 [-3.965, 5.632], p = 0.734, Cohen's d [95% CI] = -0.15 [-0.78, 0.49]) and in head and neck cancer-specific QOL (B [95% CI] = 0.061 [-4.061, 4.182], p = 0.977, Cohen's d [95% CI] = -0.05 [-0.68, 0.59]) were observed in the intervention group compared with the control. CONCLUSIONS:The educational intervention program is feasible and has promising effects on relieving the cluster. 10.1016/j.ejon.2021.101980
    Exploring the efficacy of an electronic symptom assessment and self-care intervention to preserve physical function in individuals receiving neurotoxic chemotherapy. Knoerl Robert,Weller Edie,Halpenny Barbara,Berry Donna BMC cancer BACKGROUND:Impaired physical function due to chemotherapy-induced peripheral neuropathy (CIPN) symptoms may lead to diminished quality of life. However, even with the knowledge of the effects of CIPN on physical function, clinicians infrequently assess and manage CIPN. Interventions that prioritize the early identification of CIPN to provide prompt treatment may reduce the impact of CIPN on physical function. The purpose of this paper is to compare self-reported physical function in individuals receiving neurotoxic chemotherapy between Electronic Symptom Assessment-Cancer (ESRA-C) intervention group (e.g., opportunity for symptom screening, self-care recommendations, communication coaching, and symptom tracking) and control group participants (i.e., electronic assessment alone). Secondary outcomes include pain intensity, sensory/motor CIPN, depression, fatigue, and insomnia. METHODS:The data used in this paper are a subset of a randomized controlled trial that examined the impact of the ESRA-C intervention on symptom distress in individuals receiving cancer treatment. Since the interest in this analysis is on the effects of neurotoxic chemotherapy on physical function, subjects were included if they received platinum and/or taxane-based chemotherapy and completed the baseline and end-of-treatment measures. Participants completed standardized questionnaires of physical function, CIPN, fatigue, depression, pain intensity, and insomnia prior to treatment, 3-6 weeks after treatment initiation, and after the completion of treatment. Changes in mean scores are compared between groups using linear mixed models adjusting for age. RESULTS:Intervention group participants reported significantly less reduction in physical functioning (baseline: 87.4/100; end-of-treatment: 84.5/100) relative to the control (baseline: 90.2/100; end-of-treatment: 81.8/100) (p = 0.011). For secondary measures, significantly less depression (p = 0.005) was observed in the intervention group as compared to the control, but otherwise, there were no between-group differences. Among participants who received high cumulative doses of neurotoxic chemotherapy, the intervention group reported significantly less severe sensory (p = 0.007) and motor CIPN (p = 0.039) relative to the control. CONCLUSION:Use of the ESRA-C intervention led to less reduction in physical function in comparison to the control in individuals receiving neurotoxic chemotherapy. Further research is needed to confirm our findings and to identify how electronic symptom assessment technology may mediate physical function preservation. TRIAL REGISTRATION:ClinicalTrials.Gov NCT00852852 . Registered 27 February 2009. 10.1186/s12885-018-5093-z
    Implementing an evidence-based somatic acupressure intervention in breast cancer survivors with the symptom cluster of fatigue, sleep disturbance and depression: study protocol of a phase II randomised controlled trial. BMJ open INTRODUCTION:The fatigue-sleep disturbance-depression (FSD) symptom cluster, as one of the most common symptom clusters in breast cancer (BC) survivors, can significantly decrease patients' quality of life. Since the management of the FSD symptom cluster has been unsatisfactory with the use of pharmacological treatments alone, non-pharmacological approaches have, therefore, been recommended. Somatic acupressure (SA) is a promising approach given its potential benefits of cancer-related symptom alleviation and the convenience of self-practice. However, research evidence on using acupressure to manage the FSD symptom cluster has been limited. The proposed trial aims to examine the feasibility and preliminary effects of an evidence-based SA intervention for FSD symptom cluster management in BC survivors. METHODS AND ANALYSIS:This study will be a phase II randomised controlled trial with three study arms and 1:1:1 allocation. Fifty-one early-stage BC survivors who are experiencing the FSD symptom cluster will be randomly assigned to a true SA group, a sham SA group or a usual care group. All participants will receive an education booklet regarding FSD symptom cluster management advice as the usual care package. The participants in the true SA group will additionally receive a 7-week self-administered SA intervention. The participants in the sham SA group will additionally receive self-administered light acupressure at non-acupoints with the same frequency, session and duration as the true SA group. The primary outcomes will be feasibility outcomes related to subject recruitment and completion of study questionnaires and interventions. The secondary outcomes will be the effects of SA on fatigue, sleep disturbance, depression and quality of life. Descriptive statistics will be used to present all the outcomes. The secondary outcomes will be analysed using an intent-to-treat approach. ETHICS AND DISSEMINATION:Ethical approvals of this trial have been granted by the Human Research Ethics Committee at Charles Darwin University (H19017) and the Clinical Trial Ethics Committee at The Affiliated Hospital of Southwest Medical University (KY2019039). Findings from this trial will be published in peer-reviewed journals and presented at professional conferences. TRIAL REGISTRATION NUMBER:This trial was registered at ClinicalTrials.gov and the registration number is NCT04118140, with the stage at Recruiting. 10.1136/bmjopen-2021-054597
    Intervention for Symptom Cluster Management of Fatigue, Loss of Appetite, and Anxiety among Patients with Lung Cancer undergoing Chemotherapy. Khamboon Thidarat,Pakanta Intira Asia-Pacific journal of oncology nursing Objective:Patients with lung cancer can experience various distressing symptoms. The present study aims to use symptom cluster management intervention based on symptom management theory to moderate the severity of symptom clusters, including fatigue, loss of appetite, and anxiety, in patients with lung cancer undergoing chemotherapy. Methods:A quasi-experimental study was conducted using historical controls to assess and compare the effect of a novel symptom cluster management intervention on the severity of fatigue, loss of appetite, and anxiety in patients with lung cancer undergoing chemotherapy. Lung cancer patients were recruited from an outpatient chemotherapy unit at a university hospital in Thailand. Eighty participants were assigned equally to the experimental and control groups. The study outcomes, including fatigue, loss of appetite, and anxiety, were assessed with the Edmonton Symptom Assessment System at baseline and days 7, 14, and 28 postintervention. Repeated-measures ANOVA was analyzed to determine mean differences between groups across time. Results:Overall, anxiety decreased gradually on days 7, 14, and 28 ( < 0.001 for all time points) in the experimental group. Fatigue and loss of appetite also declined after days 14 ( < 0.001) and 28 ( < 0.001) compared to baseline. The significant effects of the interaction terms time × group ( < 0.001) for all symptoms within the cluster indicate the benefit of the intervention over time. Conclusions:The pattern of changes in the symptom cluster across the study period was significantly different between the two study groups. Patients in the experimental group reported an improvement in fatigue, loss of appetite, and anxiety over time after receiving the intervention. The results suggested that the symptom cluster management intervention provided a promising approach for the simultaneous treatment of multiple symptoms within a cluster. 10.4103/2347-5625.311003
    Symptom Clusters and Influencing Factors in Family Caregivers of Individuals With Cancer. Lee Lena J,Wehrlen Leslie,Wallen Gwenyth R,Ding Ya,Ross Alyson Cancer nursing BACKGROUND:A symptom cluster is a group of 2 or more symptoms that occur together and are related to each other. Although family caregivers of individuals with cancer experience multiple concurrent symptoms, the majority of symptom research has focused on assessing and managing individual, isolated symptoms. OBJECTIVE:The study purpose was to investigate symptom clusters in cancer caregivers and to explore factors that influence symptom clusters. METHODS:Cluster analysis was performed using cross-sectional survey data from 129 family caregivers of individuals receiving cancer treatment at the National Institutes of Health Clinical Center. PROMIS (Patient-Reported Outcomes Measurement Information System) measures of 5 common symptoms in caregivers (fatigue, sleep disturbance, depression, anxiety, impaired cognition) were used to identify symptom clusters. RESULTS:Two symptom cluster groups were identified: low symptom burden (n = 106, 82.2%) and high symptom burden (n = 23, 17.8%). Individuals who reported higher levels of caregiving burden (impact on health subscale) (β = 1.31, P = .005) and loneliness (β = 0.18, P = .024) were significantly more likely to be in the high symptom burden group. CONCLUSIONS:This study provides evidence that 5 key symptoms among cancer caregivers appear to cluster into 2 groups, those with low symptom burden and those with high symptom burden. Caregiving burden (impact of health) and loneliness were significant factors differentiating symptom cluster membership. IMPLICATIONS FOR PRACTICE:Identifying symptom clusters may lead to better prevention and treatment strategies that target symptoms in cancer caregivers. Identifying factors that place a group at high risk of symptom burden can be used to guide individualized and tailored interventions. 10.1097/NCC.0000000000000877
    Associations between gender, disease features and symptom burden in patients with myeloproliferative neoplasms: an analysis by the MPN QOL International Working Group. Geyer Holly L,Kosiorek Heidi,Dueck Amylou C,Scherber Robyn,Slot Stefanie,Zweegman Sonja,Te Boekhorst Peter Aw,Senyak Zhenya,Schouten Harry C,Sackmann Federico,Fuentes Ana Kerguelen,Hernández-Maraver Dolores,Pahl Heike L,Griesshammer Martin,Stegelmann Frank,Döhner Konstanze,Lehmann Thomas,Bonatz Karin,Reiter Andreas,Boyer Francoise,Etienne Gabriel,Ianotto Jean-Christophe,Ranta Dana,Roy Lydia,Cahn Jean-Yves,Harrison Claire N,Radia Deepti,Muxi Pablo,Maldonado Norman,Besses Carlos,Cervantes Francisco,Johansson Peter L,Barbui Tiziano,Barosi Giovanni,Vannucchi Alessandro M,Paoli Chiara,Passamonti Francesco,Andreasson Bjorn,Ferrari Maria L,Rambaldi Alessandro,Samuelsson Jan,Cannon Keith,Birgegard Gunnar,Xiao Zhijian,Xu Zefeng,Zhang Yue,Sun Xiujuan,Xu Junqing,Kiladjian Jean-Jacques,Zhang Peihong,Gale Robert Peter,Mesa Ruben A Haematologica The myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and myelofibrosis, are distinguished by their debilitating symptom profiles, life-threatening complications and profound impact on quality of life. The role gender plays in the symptomatology of myeloproliferative neoplasms remains under-investigated. In this study we evaluated how gender relates to patients' characteristics, disease complications and overall symptom expression. A total of 2,006 patients (polycythemia vera=711, essential thrombocythemia=830, myelofibrosis=460, unknown=5) were prospectively evaluated, with patients completing the Myeloproliferative Neoplasm-Symptom Assessment Form and Brief Fatigue Inventory Patient Reported Outcome tools. Information on the individual patients' characteristics, disease complications and laboratory data was collected. Consistent with known literature, most female patients were more likely to have essential thrombocythemia (48.6% versus 33.0%; P<0.001) and most male patients were more likely to have polycythemia vera (41.8% versus 30.3%; P<0.001). The rate of thrombocytopenia was higher among males than females (13.9% versus 8.2%; P<0.001) and males also had greater red-blood cell transfusion requirements (7.3% versus 4.9%; P=0.02) with shorter mean disease duration (6.4 versus 7.2 years, P=0.03). Despite there being no statistical differences in risk scores, receipt of most therapies or prior complications (hemorrhage, thrombosis), females had more severe and more frequent symptoms for most individual symptoms, along with overall total symptom score (22.8 versus 20.3; P<0.001). Females had particularly high scores for abdominal-related symptoms (abdominal pain/discomfort) and microvascular symptoms (headache, fatigue, insomnia, concentration difficulties, dizziness; all P<0.01). Despite complaining of more severe symptom burden, females had similar quality of life scores to those of males. The results of this study suggest that gender contributes to the heterogeneity of myeloproliferative neoplasms by influencing phenotypic profiles and symptom expression. 10.3324/haematol.2016.149559
    Social disparities and symptom burden in populations with advanced cancer: specialist palliative care providers' perspectives. Santos Salas Anna,Watanabe Sharon M,Tarumi Yoko,Wildeman Tracy,Hermosa García Ana M,Adewale Bisi,Duggleby Wendy Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer Disparities in access to palliative care services for populations with social disparities have been reported in Western countries. Studies indicate that these populations tend to report higher symptom distress than other population groups. We need to further investigate how social disparities influence symptom burden to improve symptom relief in these populations. PURPOSE:To examine the perspectives of specialist palliative care providers concerning the relationship between social disparities and symptom burden in populations with advanced cancer. METHODS:Two sequential qualitative studies that followed a combination of interpretive and critical methodologies. The interpretive approach was outlined by van Manen's hermeneutic phenomenology while the critical component was informed by the works of Paulo Freire. Participants involved two specialist palliative care teams from a large acute care hospital and a large cancer center in Western Canada. Participants included 11 palliative care providers including registered nurses, nurse practitioners, physicians, and pharmacists. RESULTS:Participants perceived that social conditions that might aggravate symptom burden included low income, low education, lack of social support, language barriers, and rurality. The relationship between income and symptom burden reflected diverse views. Participants identified populations prone to complex symptom burden including homeless individuals, Indigenous people, people with a history of addictions, and people with mental health or psychosocial issues. CONCLUSION:Participants perceived that social disparities may increase symptom complexity in populations with advanced cancer. Participants did not identify ethnicity and gender as influencing symptom burden. Further research is needed to examine the interactions of social disparities, patient individuality, and symptom burden. 10.1007/s00520-019-04726-z
    Longitudinal Symptom Burden Trajectories in a Population-Based Cohort of Women with Metastatic Breast Cancer: A Group-Based Trajectory Modeling Analysis. Budhwani Suman,Moineddin Rahim,Wodchis Walter P,Zimmermann Camilla,Howell Doris Current oncology (Toronto, Ont.) Understanding the symptom burden trajectory for metastatic breast cancer patients can enable the provision of appropriate supportive care for symptom management. The aim of this study was to describe the longitudinal trajectories of symptom burden for metastatic breast cancer patients at the population-level. A cohort of 995 metastatic breast cancer patients with 16,146 Edmonton Symptom Assessment System (ESAS) assessments was constructed using linked population-level health administrative databases. The patient-reported ESAS total symptom distress score (TSDS) was studied over time using group-based trajectory modeling, and covariate influences on trajectory patterns were examined. Cohort patients experienced symptom burden that could be divided into six distinct trajectories. Patients experiencing a higher baseline TSDS were likely to be classified into trajectory groups with high, uncontrolled TSDS within the study follow-up period (χ (1, = 995) = 136.25, < 0.001). Compared to patients classified in the group trajectory with the highest relative TSDS (Group 6), patients classified in the lowest relative TSDS trajectory group (Group 1) were more likely to not have comorbidities (97.34% (for Groups 1-3) vs. 91.82% (for Group 6); < 0.05), more likely to receive chemotherapy (86.52% vs. 80.50%; < 0.05), and less likely to receive palliative care (52.81% vs. 79.25%; < 0.0001). Receiving radiotherapy was a significant predictor of how symptom burden was experienced in all identified groups. Overall, metastatic breast cancer patients follow heterogeneous symptom burden trajectories over time, with some experiencing a higher, uncontrolled symptom burden. Understanding trajectories can assist in establishing risk-stratified care pathways for patients. 10.3390/curroncol28010087
    Symptom clusters: Revisiting the concept in nursing care for cancer patients. Nursing forum BACKGROUND:Studies on symptom clusters among cancer patients have been conducted intensively. However, the concept seems not to be well defined, hindering its utilization in clinical practice. AIM:The aim of this paper is to reconceptualize symptom cluster and discuss areas of future research. RESULTS:A cluster of symptoms should not be viewed as simply as a group of symptoms appearing together. It should be clinically relevant, and symptom members should be interactive or have a mutual etiology. A cluster is declared as stable if its "quality" or "nature" is remained instead of merely having the same number of symptoms. Importantly, each symptom cluster should have a sentinel symptom. The sentinel symptom could be the one that predicts the presence of the cluster or could be the one that significantly interacts with other symptoms. The search for symptom clusters, which are common among various patient groups, might be helpful in some aspects. However, to better understand them, symptom clusters should be examined in specific populations. CONCLUSION:The nature of the relationship between symptom members, clinical relevance, sentinel symptom, stability, and prevalence are important features of a symptom cluster. More explorations into these properties by future studies are suggested. 10.1111/nuf.12684
    Impact of Pre-Treatment NLR and Other Hematologic Biomarkers on the Outcomes of Early-Stage Non-Small-Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy. Aduquaye Marina,Dube Sheen,Bashir Bashir,Chowdhury Amitava,Ahmed Naseer,Leylek Ahmet,Kim Julian,Lambert Pascal,Bucher Oliver,Hunter William,Sivananthan Gokulan,Koul Rashmi,Rathod Shrinivas Current oncology (Toronto, Ont.) INTRODUCTION:We evaluated the association of pre-treatment immunologic biomarkers on the outcomes of early-stage non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS:In this retrospective study, all newly diagnosed early-stage NSCLC treated with SBRT between January 2010 and December 2017 were screened and included for further analysis. The pre-treatment neutrophil-lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were calculated. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan-Meier. Multivariable models were constructed to determine the impact of different biomarkers and the Akaike information criterion (AIC), index of adequacy, and scaled Brier scores were calculated. RESULTS:A total of 72 patients were identified and 61 were included in final analysis. The median neutrophil count at baseline was 5.4 × 10/L (IQR: 4.17-7.05 × 10/L). Median lymphocyte count was 1.63 × 10/L (IQR: 1.29-2.10 × 10/L), median monocyte count was 0.65 × 10/L (IQR: 0.54-0.83 × 10/L), median platelet count was 260.0 × 10/L (IQR: 211.0-302.0 × 10/L). The median NLR was 3.42 (IQR: 2.38-5.04), median MLR was 0.39 (IQR: 0.31-0.53), and median PLR was 156.4 (IQR: 117.2-197.5). On multivariable regression a higher NLR was associated with worse OS ( = 0.01; HR-1.26; 95% CI 1.04-1.53). The delta AIC between the two multivariable models was 3.4, suggesting a moderate impact of NLR on OS. On multivariable analysis, higher NLR was associated with poor RFS ( = 0.001; NLR^1 HR 0.36; 0.17-0.78; NLR^2 HR-1.16; 95% CI 1.06-1.26) with a nonlinear relationship. The delta AIC between the two multivariable models was 16.2, suggesting a strong impact of NLR on RFS. In our cohort, MLR and PLR were not associated with RFS or OS in multivariable models. CONCLUSIONS:Our study suggests NLR, as a biomarker of systemic inflammation, is an independent prognostic factor for OS and RFS. The nonlinear relationship with RFS may indicate a suitable immunological environment is needed for optimal SBRT action and tumoricidal mechanisms. These findings require further validation in independent cohorts. 10.3390/curroncol29010019
    Using a Patient-Centered Approach to Identify Symptom Clusters Among Adolescents With Cancer. Wu Wei-Wen,Lin Kuan-Chia,Liang Shu-Yuan,Jou Shiann-Tarng Cancer nursing BACKGROUND:Prior studies identifying symptom clusters used a symptom-centered approach to demonstrate the relationship among symptoms. Latent profile analysis (LPA) is a patient-centered approach that classifies individuals from a heterogeneous population into homogeneous subgroups, helping prioritize interventions to focus on clusters with the most severe symptom burden. OBJECTIVE:The aim of this study was to use LPA to determine the best-fit models and to identify phenotypes of severe symptom distress profiles for adolescents with cancer who are undergoing treatment and in survivorship. METHODS:We used estimated means generated by the LPA to predict the probability of an individual symptom occurring across on- and off-treatment groups for 200 adolescents with cancer. RESULTS:The 3-profile solution was considered the best fit to the data for both on- and off-treatment groups. Adolescents on treatment and classified into the severe profile were most likely to report distress in appetite, fatigue, appearance, nausea, and concentration. Adolescents off treatment and classified into the severe profile were most likely to report distress in fatigue, pain frequency, and concentration. CONCLUSIONS:Latent profile analysis provided a cluster methodology that uncovered hidden profiles from observed symptoms. This made it possible to directly compare the phenotypes of severe profiles between different treatment statuses. IMPLICATIONS FOR PRACTICE:The co-occurring 13-item Symptom Distress Scale symptoms found in the severe symptom distress profiles could be used as items in a prespecified severe symptom distress cluster, helping evaluate a patient's risk of developing varying degrees of symptom distress. 10.1097/NCC.0000000000000587
    Risk Factors for Cognitive Impairment in High-Grade Glioma Patients Treated with Postoperative Radiochemotherapy. Wang Qiang,Xiao Fengxia,Qi Fei,Song Xiaopeng,Yu Yonghua Cancer research and treatment : official journal of Korean Cancer Association PURPOSE:Fractionated radiotherapy as well as concomitant and adjuvant chemotherapy such as temozolomide for postoperative high-grade glioma (HGG) patients improves progression-free survival and overall survival. Multiple factors such as chemotherapy, radiotherapy, tumor grade, residual tumor volume, and genetic modifications might play a role in the formation of cognitive impairment. The risk factors of cognitive impairment in postoperative patients with HGG receiving radiotherapy and chemotherapy remains a concern in this population. The purpose of this study was to identify risk factors for cognitive impairment in patients of postoperative HGG. MATERIALS AND METHODS:A total of 229 patients with HGG who underwent surgery were analyzed. Cognitive impairment was defined as a decrease of Cognitive Assessment Montreal (MoCA)'s score in at least two cognitive domains or any MoCA's score of less than 26 points at the time of study compared with baseline level. Multiple potential risk factors including methylated status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter, glioma World Health Organization (WHO) grade, residual tumor volume, education, and sex were analyzed. Cox univariate and multivariate regression analysis was used to detect the significant risk factors for cognitive impairment. RESULTS:At the end of follow-up among the 229 patients, 147 patients (67%) developed cognitive impairment. 82 patients (36%) remained in normal cognitive condition. In multivariate analysis, unmethylated MGMT promoter (hazard ratio [HR], 1.679; 95% confidence interval [CI], 1.212 to 2.326; p=0.002), glioblastoma (HR, 1.550; 95% CI, 1.117 to 2.149; p=0.009), and residual tumor volume > 5.58 cm3 (HR, 1.454; 95% CI, 1.047 to 2.020; p=0.026) were independent risk factors for cognitive impairment. CONCLUSION:Methylated status of the MGMT promoter, glioma WHO grade, and residual tumor volume might be risk factors for the cognitive impairment in postoperative patients with HGG. 10.4143/crt.2019.242
    Role of Exosomes in Cancer-Related Cognitive Impairment. Koh Yong Qin,Tan Chia Jie,Toh Yi Long,Sze Siu Kwan,Ho Han Kiat,Limoli Charles L,Chan Alexandre International journal of molecular sciences A decline in cognitive function following cancer treatment is one of the most commonly reported post-treatment symptoms among patients with cancer and those in remission, and include memory, processing speed, and executive function. A clear understanding of cognitive impairment as a result of cancer and its therapy can be obtained by delineating structural and functional changes using brain imaging studies and neurocognitive assessments. There is also a need to determine the underlying mechanisms and pathways that impact the brain and affect cognitive functioning in cancer survivors. Exosomes are small cell-derived vesicles formed by the inward budding of multivesicular bodies, and are released into the extracellular environment via an exocytic pathway. Growing evidence suggests that exosomes contribute to various physiological and pathological conditions, including neurological processes such as synaptic plasticity, neuronal stress response, cell-to-cell communication, and neurogenesis. In this review, we summarize the relationship between exosomes and cancer-related cognitive impairment. Unraveling exosomes' actions and effects on the microenvironment of the brain, which impacts cognitive functioning, is critical for the development of exosome-based therapeutics for cancer-related cognitive impairment. 10.3390/ijms21082755
    Prechemotherapy Levels of Plasma Dehydroepiandrosterone and Its Sulfated Form as Predictors of Cancer-Related Cognitive Impairment in Patients with Breast Cancer Receiving Chemotherapy. Toh Yi Long,Shariq Mujtaba Juliana,Bansal Sumit,Yeo Angie,Shwe Maung,Lau Aik Jiang,Chan Alexandre Pharmacotherapy STUDY OBJECTIVE:Dehydroepiandrosterone (DHEA) and its sulfated form (DHEAS)-jointly referred to as DHEA(S)-are neurosteroids known to regulate brain development and function that have been found to be positively correlated with cognitive function. It is unknown whether prechemotherapy plasma DHEA(S) levels are associated with the onset of cancer-related cognitive impairment (CRCI). The objective of this study was to evaluate whether an association exists between prechemotherapy plasma DHEA(S) levels and onset of CRCI in patients with breast cancer receiving chemotherapy. DESIGN:Multicenter, prospective cohort study. SETTING:Two specialized cancer centers in Singapore. PATIENTS:Eighty-one patients with early-stage breast cancer (stages I-III) who had no prior exposure to chemotherapy and/or radiotherapy and were scheduled to receive anthracycline-based or taxane-based chemotherapy treatment with curative intent. MEASUREMENTS AND MAIN RESULTS:Patients completed assessments for self-perceived and objective cognitive function at three time points: prechemotherapy (T1), during chemotherapy (T2), and after chemotherapy (T3). Plasma samples were collected prior to chemotherapy, and DHEA(S) levels were quantified by using ultra-high-performance liquid chromatography-tandem mass spectrometry. Multivariable logistic regression was used to adjust for clinically important factors and to evaluate the association between prechemotherapy plasma DHEA(S) levels and CRCI. Mean ± SD age was 48.9 ± 9.3 years, with 27.8% of patients experiencing clinically significant cognitive impairment based on global Functional Assessment of Cancer Therapy-Cognitive Function scores. The mean ± SD prechemotherapy plasma DHEAS and DHEA levels were 1.61 ± 0.91 μmol/L and 19.21 ± 13.13 nmol/L, respectively. Prechemotherapy DHEAS levels were found to be associated with impairment in the self-perceived cognitive domains of verbal fluency (adjusted odds ratio [OR] 0.27, 95% confidence interval [CI] 0.08-0.96) and mental acuity (adjusted OR 0.25, 95% CI 0.08-0.74). Conversely, DHEA levels were not associated with impairment in any cognitive subdomains. CONCLUSION:Our findings suggest that patients with higher prechemotherapy DHEAS levels had lower odds of developing self-perceived cognitive impairment. Future studies are required to further investigate the effect of DHEA(S) on specific cognitive domains and to validate our findings in independent cohorts. 10.1002/phar.2259
    Association between cognitive impairment patient with solid cancer and insulin resistance. Gonda Kenji,Yaginuma Kenji,Rokkaku Yuichi,Horita Shoichiro,Maejima Yuko,Shimomura Kenju BMC research notes OBJECTIVES:In an aging population, an increase in the number of elderly cancer patients with cognitive impairment is expected. The possible association between cancer and cognitive impairment is important to elucidate, because it can have a serious impact on quality of life. Here, we focused on glucose metabolism as a factor that links cancer and cognitive impairment. RESULTS:Thirteen subjects with solid cancers and cognitive impairment were recruited. As a control group, 14 subjects with cognitive impairment alone and 8 subjects with cancer alone were recruited. A Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and that of β-cell function (HOMA-B) were used. In comparison with patients with solid cancer alone, those with cognitive impairment alone and those with both cancer and cognitive impairment had increased HOMA-IR values. Insulin resistance was increased in patients with cognitive impairment alone and those with both cognitive impairment and solid cancer than in patients without cognitive impairment; however, β-cell function was not affected. The present data indicated that elderly cancer patients with high HOMA-IR score may be at a relatively high risk for developing cognitive impairment. Furthermore, early treatment to reduce insulin sensitivity may prevent cognitive impairment. 10.1186/s13104-019-4739-5
    Correlates of cognitive impairment in adult cancer survivors who have received chemotherapy and report cognitive problems. Gutenkunst Shannon L,Vardy Janette L,Dhillon Haryana M,Bell Melanie L Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer OBJECTIVE:Cognitive impairment negatively affects some cancer survivors who have completed chemotherapy; however, factors underlying this cognitive impairment remain poorly understood. We aimed to investigate (1) the relative importance of demographics, medical, and psychological characteristics associated with cognitive impairment and (2) the specific variables associated with cognitive impairment in adult cancer survivors who completed adjuvant chemotherapy. METHODS:We performed post hoc analyses of baseline data from early-stage cancer survivors with cognitive complaints who received adjuvant chemotherapy 0.5-5 years earlier and volunteered for a trial designed to improve cognition. The primary outcome of self-reported cognitive impairment was measured using a questionnaire; secondary outcome of objective cognitive impairment was measured using a computerized neuropsychological test battery. Hierarchical linear regression determined the relative importance of demographics, medical, and psychological characteristics in associations with both self-reported and objective cognitive impairment. RESULTS:The sample was 95% female and 89% breast cancer patients. The final model accounted for 33% of variation in self-reported cognitive impairment (n = 212, demographics 5%, medical 3%, and psychological 25%), with fatigue and stress as significant individual correlates (p values ≤ 0.0001). For the secondary analysis, the final model accounted for 19% of variation in objective cognitive impairment (n = 206, demographics 10%, medical 5%, and psychological 4%), with age, smoking history, and number of chemotherapy cycles as significant individual correlates. CONCLUSION:We found that psychological characteristics are more important than demographic and medical characteristics in self-reported cognitive impairment, whereas other characteristics are more important in objective cognitive impairment. This suggests clinicians should investigate possible psychological problems in cancer survivors who self-report cognitive impairment. 10.1007/s00520-020-05616-5
    Symptom Biomarkers for Children Receiving Treatment for Cancer: State of the Science. Mandrell Belinda N,Withycombe Janice S Journal of pediatric oncology nursing : official journal of the Association of Pediatric Oncology Nurses The Children's Oncology Group Nursing Discipline has identified the most concerning symptoms during childhood cancer treatment and the need for continued symptom assessment and intervention during treatment trajectory. To develop appropriate interventions, symptom science strategies must explore the biological mechanisms associated with symptoms of cancer and cancer treatment. To explore the associated biological mechanisms, biomarkers have been recommended for inclusion in symptom science studies, when applicable. The biomarker assessed, as well as the method of collection and storage, can affect the reliability and validity of the study results and clinical implication. This review will describe biomarkers that have been described in pediatric oncology symptom science research and provides special considerations for specimen collection and processing. 10.1177/1043454219859233
    Depressive symptom-associated IL-1β and TNF-α release correlates with impaired bronchodilator response and neutrophilic airway inflammation in asthma. Zhang Li,Zhang Xin,Zheng Jing,Liu Ying,Wang Ji,Wang Gang,Zhang Hong Ping,Kang De Ying,Peng Zu Gui,Ji Yu Lin,Wang Lei,Gibson Peter Gerard,Wang Gang Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology BACKGROUND:Depressive symptoms worsen asthma outcomes; however, the mechanism remains largely unexplored. OBJECTIVE:This study aimed to determine whether depressive symptom-associated immune inflammation correlates with impaired bronchodilator response (BDR) and airway inflammatory phenotypes. METHODS:Eligible adults with asthma (n = 198) underwent clinical assessment, sputum induction and blood sampling. Depressive symptoms were defined by scores on the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). Pre- and post-bronchodilator spirometry was performed for BDR. Airway inflammatory phenotypes were defined by sputum cell counts. CRP, IL-1β, IL-5, IL-6, IL-8, TNF-α, IFN-γ, CCL17 and CCL22 in serum and sputum were detected. RESULTS:Compared with the non-depressive group (n = 174), the depressive group (n = 24) exhibited impaired BDR (P = 0.032) and increased sputum neutrophils (P = 0.023), which correlated with the HADS-D scores (P = 0.027 and P = 0.029). Levels of IL-1β, TNF-α and IFN-γ in the serum and those of IL-1β and IFN-γ in the sputum were elevated in the depressive group compared to those in the non-depressive group (all P < 0.05). Multiple regression models indicated that TNF-α in the sputum and IL-1β, IL-6 and IFN-γ in both the serum and sputum were inversely associated with BDR; TNF-α in the sputum and IL-1β in both the serum and sputum were positively correlated with sputum neutrophils. Mediation analyses revealed that IL-1β and TNF-α in the sputum and IL-1β in both the serum and sputum mediate the correlations of the HADS-D scores with BDR and sputum neutrophils, respectively. CONCLUSIONS AND CLINICAL RELEVANCE:Asthma patients with depressive symptoms present worse asthma control, which is most likely explained by impaired BDR and neutrophilic airway inflammation. IL-1β and TNF-α, which are two key pro-inflammatory cytokines that mediate the correlation of depressive symptoms with impaired BDR and neutrophilic airway inflammation, may serve as targeted biomarkers in the neuropsychological phenotype of asthma; however, this result needs to be further validated. 10.1111/cea.13346
    Association of Inflammatory Cytokines With the Symptom Cluster of Pain, Fatigue, Depression, and Sleep Disturbance in Chinese Patients With Cancer. Ji Yan-Bo,Bo Chun-Lu,Xue Xiu-Juan,Weng En-Ming,Gao Guang-Chao,Dai Bei-Bei,Ding Kai-Wen,Xu Cui-Ping Journal of pain and symptom management CONTEXT:Pain, fatigue, depression, and sleep disturbance are common in patients with cancer and usually co-occur as a symptom cluster. However, the mechanism underlying this symptom cluster is unclear. OBJECTIVES:This study aimed to identify subgroups of cluster symptoms, compare demographic and clinical characteristics between subgroups, and examine the associations between inflammatory cytokines and cluster symptoms. METHODS:Participants were 170 Chinese inpatients with cancer from two tertiary hospitals. Inflammatory markers including interleukin-6 (IL-6), interleukin-1 receptor antagonist, and tumor necrosis factor alpha were measured. Intergroup differences and associations of inflammatory cytokines with the cluster symptoms were examined with one-way analyses of variance and logistic regression. RESULTS:Based on cluster analysis, participants were categorized into Subgroup 1 (all low symptoms), Subgroup 2 (low pain and moderate fatigue), or Subgroup 3 (moderate-to-high on all symptoms). The three subgroups differed significantly in Eastern Cooperative Oncology Group (ECOG) performance status, sex, residence, current treatment, education, economic status, and inflammatory cytokines levels (all P < 0.05). Compared with Subgroup 1, Subgroup 3 had a significantly poorer ECOG physical performance status and higher IL-6 levels, were more often treated with combined chemoradiotherapy, and were more likely to be rural residents. IL-6 and ECOG physical performance status were significantly associated with 1.246-fold (95% CI 1.114-1.396) and 31.831-fold (95% CI 6.017-168.385) increased risk of Subgroup 3. CONCLUSION:Our findings suggest that IL-6 levels are associated with cluster symptoms in cancer patients. Clinicians should identify patients at risk for more severe symptoms and formulate novel target interventions to improve symptom management. 10.1016/j.jpainsymman.2017.05.003
    C-Reactive Protein/Albumin Ratio Is an Independent Prognostic Predictor of Survival in Advanced Cancer Patients Receiving Palliative Care. Zhang Jing,Zhang Chenbo,Li Qingxian,Zhang Jiawen,Gu Xiaoli,Zhao Weiwei,Chen Menglei,Liu Minghui,Zhang Zhe,Liao Xinghe,Cheng Wenwu Journal of palliative medicine The C-reactive protein/albumin (CRP/Alb) ratio has been reported as a prognostic factor of survival for patients with a variety of cancers. However, its prognostic impact for advanced cancer patients receiving palliative care remains presently unknown. The present study assessed the prognostic value of the CRP/Alb ratio, and compared this with that of the Glasgow Prognostic Score (GPS) and Palliative Prognostic Index (PPI) in a cohort of advanced cancer patients receiving palliative therapy. The medical records of 262 eligible patients who died of advanced cancer from February 1, 2013 to December 30, 2017 in the palliative care unit of the Fudan University Shanghai Cancer Center were retrospectively reviewed for the analysis. The present results revealed that a CRP/Alb ratio ≥1.31 (hazard ratio [HR], 2.33 [1.78-3.05],  < 0.001) can predict poor prognosis through univariate analysis. In addition, the multivariate analysis revealed that CRP/Alb (HR, 2.09 [1.54-2.84],  < 0.001), GPS (HR, 1.81 [1.07-3.07],  < 0.001), and PPI (HR, 3.35 [2.25-4.99],  < 0.001) were all independent prognosis factors. To compare the discriminatory performance of the CRP/Alb ratio with that of other established prognostic indexes in palliative care settings, the c-statistics, integrated discriminatory improvement index, net reclassification index, and receiver operating characteristic curves were generated, and it was demonstrated that the CRP/Alb ratio (c-statistics, 0.64 [0.61-0.68]) was able to discriminate advanced cancer patients with different survivals, with analogous discriminatory ability as GPS (c-statistics, 0.63 [0.59-0.66]) and PPI (c-statistics, 0.64 [0.60-0.68]). Notably, the combination of multiple prognostic indexes exerted higher discriminatory ability, compared with any single predictive index (c-statistics, 0.69 [0.66-0.73],  < 0.001). The present study suggests that the CRP/Alb ratio is a promising prognostic factor in predicting cancer patient survival in palliative care settings. Incorporating both objective parameters and the subjective index may improve the prediction accuracy of prognosis. 10.1089/jpm.2019.0102
    Development and validation of oral chemotherapy self-management scale. Peng Qi,Wu Wanying BMC cancer BACKGROUND:With the increase of oral chemotherapy drugs, patients receiving cancer treatment prefer oral chemotherapy versus intravenous, given equal efficacy and toxicity. However, they need to take an active part in their care, which is vital with home-based oral therapy, therefore the self-management is important for patients with oral chemotherapy. Unfortunately, the development of self-management assessment tools for oral chemotherapy still lags behind. METHODS:The OCSMS item pool was formulated based on literature review and semi-structured interviews, An initial scale containing 5 dimensions and 38 items was constructed through research seminar, Delphi survey and pilot testing. To assess the validity and reliability, We recruited 261 patients from cancer hospital in China. RESULTS:A 36-item scale was developed with five dimensions identified through factor analysis: daily life management, symptom management, medication management, emotional cognitive management and social support. Cronbach's coefficient Alpha, split-half coefficient, test-retest reliability and S-CVI/UA scores were 0.929, 0.773, 0.966 and 0.833, respectively, indicating that OCSMS has good reliability and validity. CONCLUSIONS:The OCSMS is a valid, reliable measurement method of the self-management ability of patients with oral chemotherapy. The OCSMS shows potential as a tool to ensure the safety of patients with cancer. The OCSMS may help evaluate the effectiveness of interventions to improve the self-management ability of patients. 10.1186/s12885-020-07404-0
    Effects of a nurse-led medication self-management programme in women with oral treatments for metastatic breast cancer: A mixed-method randomised controlled trial. Komatsu Hiroko,Yagasaki Kaori,Yamaguchi Takuhiro,Mori Ayako,Kawano Hiromi,Minamoto Noriko,Honma Orie,Tamura Kenji European journal of oncology nursing : the official journal of European Oncology Nursing Society PURPOSE:Adherence to medication is the most important challenge facing patients receiving oral anticancer treatment. This study aimed to evaluate the effects of a patient-centred medication self-management support programme in patients with metastatic breast cancer undergoing oral anticancer treatment. METHODS:This trial was a two-phased mixed-method randomised controlled study. Eligible participants were 155 patients with metastatic breast cancer newly prescribed an oral chemotherapy or targeted therapy agent. The intervention group received the patient-centred medication self-management support programme conducted by trained nurses. Primary outcome was adherence to medication at three months after the commencement of treatment, calculated by medication possession ratio (MPR). Secondary outcomes included self-efficacy, functional assessment, psychological distress, symptom severity and symptom interference, and patient satisfaction. After the completion of the intervention study, focus group interviews were conducted among intervention nurses. RESULTS:Both intervention and control groups maintained more than 90% of MPR and no significant difference was observed in the primary outcome. Regarding secondary outcomes, only general self-efficacy was significantly different in the two groups. In the qualitative study, the intervention nurses perceived improvement in the patients' self-efficacy, ability to anticipate the impact of treatment and adjust to life, and avoidance of loneliness. CONCLUSIONS:A significant effect of the programme was not found in the program because the adherence rate was high in both groups. Improvement in the patients' self-efficacy was observed both quantitatively and qualitatively. TRIAL REGISTRATION:UMIN Clinical Trials Registry (UMIN-CTR), Japan, UMIN000016597. (27 February 2015). 10.1016/j.ejon.2020.101780
    Biomarkers as Common Data Elements for Symptom and Self-Management Science. Page Gayle G,Corwin Elizabeth J,Dorsey Susan G,Redeker Nancy S,McCloskey Donna Jo,Austin Joan K,Guthrie Barbara J,Moore Shirley M,Barton Debra,Kim Miyong T,Docherty Sharron L,Waldrop-Valverde Drenna,Bailey Donald E,Schiffman Rachel F,Starkweather Angela,Ward Teresa M,Bakken Suzanne,Hickey Kathleen T,Renn Cynthia L,Grady Patricia Journal of nursing scholarship : an official publication of Sigma Theta Tau International Honor Society of Nursing PURPOSE:Biomarkers as common data elements (CDEs) are important for the characterization of biobehavioral symptoms given that once a biologic moderator or mediator is identified, biologically based strategies can be investigated for treatment efforts. Just as a symptom inventory reflects a symptom experience, a biomarker is an indicator of the symptom, though not the symptom per se. The purposes of this position paper are to (a) identify a "minimum set" of biomarkers for consideration as CDEs in symptom and self-management science, specifically biochemical biomarkers; (b) evaluate the benefits and limitations of such a limited array of biomarkers with implications for symptom science; (c) propose a strategy for the collection of the endorsed minimum set of biologic samples to be employed as CDEs for symptom science; and (d) conceptualize this minimum set of biomarkers consistent with National Institute of Nursing Research (NINR) symptoms of fatigue, depression, cognition, pain, and sleep disturbance. DESIGN AND METHODS:From May 2016 through January 2017, a working group consisting of a subset of the Directors of the NINR Centers of Excellence funded by P20 or P30 mechanisms and NINR staff met bimonthly via telephone to develop this position paper suggesting the addition of biomarkers as CDEs. The full group of Directors reviewed drafts, provided critiques and suggestions, recommended the minimum set of biomarkers, and approved the completed document. Best practices for selecting, identifying, and using biological CDEs as well as challenges to the use of biological CDEs for symptom and self-management science are described. Current platforms for sample outcome sharing are presented. Finally, biological CDEs for symptom and self-management science are proposed along with implications for future research and use of CDEs in these areas. FINDINGS:The recommended minimum set of biomarker CDEs include pro- and anti-inflammatory cytokines, a hypothalamic-pituitary-adrenal axis marker, cortisol, the neuropeptide brain-derived neurotrophic factor, and DNA polymorphisms. CONCLUSIONS:It is anticipated that this minimum set of biomarker CDEs will be refined as knowledge regarding biologic mechanisms underlying symptom and self-management science further develop. The incorporation of biological CDEs may provide insights into mechanisms of symptoms, effectiveness of proposed interventions, and applicability of chosen theoretical frameworks. Similarly, as for the previously suggested NINR CDEs for behavioral symptoms and self-management of chronic conditions, biological CDEs offer the potential for collaborative efforts that will strengthen symptom and self-management science. CLINICAL RELEVANCE:The use of biomarker CDEs in biobehavioral symptoms research will facilitate the reproducibility and generalizability of research findings and benefit symptom and self-management science. 10.1111/jnu.12378
    Symptom Clusters and Influencing Factors in Children With Acute Leukemia During Chemotherapy. Li Rongrong,Ma Jinling,Chan Yuying,Yang Qi,Zhang Chunxu Cancer nursing BACKGROUND:Acute leukemia is the most common malignancy in childhood. Identification of symptom clusters and their influencing factors in children with acute leukemia may improve the management of symptoms. OBJECTIVE:The aims of this study were to investigate symptom clusters in children with acute leukemia during chemotherapy and analyze the factors influencing their severity. METHODS:A cross-sectional survey was administered to 159 Chinese children with acute leukemia during chemotherapy. A demographic questionnaire and the Memorial Symptom Assessment Scale 10-18 were completed by the patients and their parents. Exploratory factor analysis was used to identify symptom clusters. Univariate analyses and multiple linear regression analyses were performed to analyze the factors affecting symptom clusters. RESULTS:Six clusters were identified, including gastrointestinal cluster, emotional cluster, head-related cluster, self-image disorder cluster, skin itching/irritation cluster, and somatic cluster. Factors influencing the severity of symptom clusters included age, gender, stage of chemotherapy, and medical reimbursement. CONCLUSIONS:There are multiple symptom clusters in children with acute leukemia during chemotherapy. Medical care staff should manage symptoms from the perspective of symptom cluster and carry out personalized interventions according to factors influencing these clusters. IMPLICATIONS FOR PRACTICE:The ability to predict symptom clusters in children with acute leukemia undergoing chemotherapy may assist with optimal clinical decision making in order to alleviate the symptom burden and improve children's quality of life. 10.1097/NCC.0000000000000716
    The level of oxidative stress and the expression of genes involved in DNA-damage signaling pathways in depressive patients with colorectal carcinoma. Wei Yong-chang,Zhou Fu-ling,He Da-lin,Bai Ji-rong,Hui Ling-yun,Wang Xin-yang,Nan Ke-jun Journal of psychosomatic research OBJECTIVES:This study investigated the connection among the oxidative stress, depression and expression of specific genes involved in DNA-damage signaling pathways in patients with colorectal carcinoma (CRC). METHODS:A unique Dukes'C subset of patients with newly diagnosed colorectal adenocarcinoma were assessed using the Hamilton Depression Rating Scale (HAMD), Zung Self-rating Depression Scale (SDS), Zung Self-rating Anxiety Scale (SAS), Symptom Checklist 90 (SCL-90) and other multiple-item questionnaires. Oxidative-stress-related parameters in sera and the expression of genes were monitored during a pretreatment period. RESULTS:Eighty-two eligibility cases were divided into 2 groups based on an HAMD score cutoff of 20: the mean score was 28.29 in Group A (depression, n=52) and 16.50 in Group B (nondepression, n=30). The serum total antioxidant capacity, catalase, and superoxide dismutase concentrations were lower in Group A, whereas those of nitric oxide and malondialdehyde were higher in Group A. Importantly, the 8-hydroxy-deoxyguanosine level was higher in Group A than in Group B (P<.05). Microarray analysis revealed that the expressions of p34, PA26, and ABL were higher in Group A, whereas those of HRAD51, CR6, and XRCC3 were higher in Group B. CONCLUSION:Oxidative stress is capable of causing neuronal toxicity via lipid peroxidation, DNA damage, and abnormalities of gene expression, and therefore is a possible pathogenic mechanism underlying depression in patients with CRC. 10.1016/j.jpsychores.2008.09.001
    Self-care as a mediator between symptom-management self-efficacy and quality of life in women with breast cancer. Chin Chia-Hui,Tseng Ling-Ming,Chao Ta-Chung,Wang Tsae-Jyy,Wu Shu-Fang,Liang Shu-Yuan PloS one BACKGROUND:The important role of self-efficacy in facilitating health behavior and, in turn, promoting health outcomes has been widely presumed in the theoretical literature. However, little research has focused on the mechanism by which self-care mediates the relationship between symptom-management self-efficacy and quality of life (QOL) in breast cancer patients. OBJECTIVE:The purpose of this study was to examine the relationship between symptom-management self-efficacy and quality of life in Taiwanese oncology outpatients with breast cancer and then proposes self-care as a mediator between these two factors. METHODS:This cross-sectional study enrolled 201 oncology outpatients at one teaching hospital in metropolitan Taipei City, Taiwan. The research instruments included the Symptom-Management Self-Efficacy Scale-Cancer (SMSES-Breast Ca.), the Self-Care Scale, and the European Organization for Research & Treatment of Cancer Quality of Life Group Questionnaire (EORTC-QLQ-C30). RESULTS:Symptom-management self-efficacy (SMSE) was directly associated with the QOL of the participants (β = 5.94, p < .001). Moreover, SMSE was indirectly associated with QOL through self-care. Self-care was found to mediate the relationship between symptom-management self-efficacy and global QOL (indirect effect = 0.54, 95% CI 0.12 to 1.18). The level of 95% CI was significant. CONCLUSIONS:The present study supports that self-efficacy beliefs and self-care both significantly and positively influence the quality of life of patients. 10.1371/journal.pone.0246430
    Symptom burden among older breast cancer survivors: The Thinking and Living With Cancer (TLC) study. Cancer BACKGROUND:Little is known about longitudinal symptom burden, its consequences for well-being, and whether lifestyle moderates the burden in older survivors. METHODS:The authors report on 36-month data from survivors aged ≥60 years with newly diagnosed, nonmetastatic breast cancer and noncancer controls recruited from August 2010 through June 2016. Symptom burden was measured as the sum of self-reported symptoms/diseases as follows: pain (yes or no), fatigue (on the Functional Assessment of Cancer Therapy [FACT]-Fatigue scale), cognitive (on the FACT-Cognitive scale), sleep problems (yes or no), depression (on the Center for Epidemiologic Studies Depression scale), anxiety (on the State-Trait Anxiety Inventory), and cardiac problems and neuropathy (yes or no). Well-being was measured using the FACT-General scale, with scores from 0 to 100. Lifestyle included smoking, alcohol use, body mass index, physical activity, and leisure activities. Mixed models assessed relations between treatment group (chemotherapy with or without hormone therapy, hormone therapy only, and controls) and symptom burden, lifestyle, and covariates. Separate models tested the effects of fluctuations in symptom burden and lifestyle on function. RESULTS:All groups reported high baseline symptoms, and levels remained high over time; differences between survivors and controls were most notable for cognitive and sleep problems, anxiety, and neuropathy. The adjusted burden score was highest among chemotherapy-exposed survivors, followed by hormone therapy-exposed survivors versus controls (P < .001). The burden score was related to physical, emotional, and functional well-being (eg, survivors with lower vs higher burden scores had 12.4-point higher physical well-being scores). The composite lifestyle score was not related to symptom burden or well-being, but physical activity was significantly associated with each outcome (P < .005). CONCLUSIONS:Cancer and its treatments are associated with a higher level of actionable symptoms and greater loss of well-being over time in older breast cancer survivors than in comparable noncancer populations, suggesting the need for surveillance and opportunities for intervention. 10.1002/cncr.32663
    Symptom burden in patients with cancer who are experiencing unplanned hospitalization. Newcomb Richard A,Nipp Ryan D,Waldman Lauren P,Greer Joseph A,Lage Daniel E,Hochberg Ephraim P,Jackson Vicki A,Fuh Charn-Xin,Ryan David P,Temel Jennifer S,El-Jawahri Areej R Cancer BACKGROUND:Inpatient supportive care programs often target patients with advanced solid tumors. To the authors' knowledge, few studies to date have characterized symptom burden in hospitalized patients with potentially curable cancers. The objective of the current study was to compare symptom burden, palliative care consultation, and readmission rates in hospitalized patients by cancer type and treatment intent. METHODS:The authors conducted a single-center study of hospitalized patients with cancer between 2014 and 2017. They assessed physical symptoms using the Edmonton Symptom Assessment System and psychological distress using the Patient Health Questionnaire-4 and the Primary Care PTSD (Posttraumatic Stress Disorder) Screen. Multivariate linear regression models were used to assess symptom burden, logistic regression was used to assess palliative care use, and competing risk regression was used to compare 90-day readmission risk. RESULTS:A total of 1549 patients were enrolled and surveyed. The majority of patients reported moderate to severe fatigue, poor well-being, and drowsiness with no significant differences noted by cancer type and treatment intent. Compared with other groups, patients with incurable solid cancer reported higher physical symptoms (beta coefficient [B], 4.73; P < .01) and symptoms of depression (B, 0.44; P < .01) and anxiety (B, 0.39; P < .01), but no difference in posttraumatic stress disorder. Among patients in the top quartile symptom burden according to the Edmonton Symptom Assessment System, the palliative care service was consulted in 14.7%, 7.9%, 25.0%, and 49.6%, respectively, of patients with potentially curable hematologic, potentially curable solid, incurable hematologic, and incurable solid cancers (P < .001). Compared with patients with potentially curable solid cancer, patients in each group experienced a higher risk of readmission within 90 days. CONCLUSIONS:Hospitalized patients with cancer experience substantial physical and psychological symptoms. Palliative care rarely is consulted for highly symptomatic patients with potentially curable cancers. Supportive care interventions should target the needs of symptomatic patients regardless of treatment intent. 10.1002/cncr.32833
    A Cognitive-Behavioral Intervention for the Symptom Clusters of Chinese Patients With Gastrointestinal Tract Cancer Undergoing Chemotherapy: A Pilot Study. Zhang Xinqiong,Wang Qin,Zhang Xiaomin,Wu Xiaoting,Wang Qiuping,Hong Jingfang Cancer nursing BACKGROUND:Patients with gastrointestinal tract (GIT) cancer undergoing chemotherapy often experience several symptoms that constitute symptom clusters and can cause patients to suffer. Effective interventions are lacking for this kind of patients. OBJECTIVE:The aims of this study were to test the feasibility and acceptability of a cognitive-behavioral (CB) intervention developed for Chinese patients with GIT cancer undergoing chemotherapy and to estimate the efficacy of the intervention for symptom clusters. METHODS:In this pilot, quasi-randomized controlled trial, 40 patients were assigned to the CB intervention or control group. The CB intervention, considering characteristics of patients and Chinese culture, contained 4 sections including cognitive reframing, cancer-diet education, relaxation, and exercise techniques. Symptom clusters, illness perception, anxiety, and depression were measured. RESULTS:Thirty-nine patients (97.5%) completed the study program and expressed willingness to follow the intervention. Compared with the control group, all outcomes were improved (all P < .05) in the CB group after the intervention, except for the gastrointestinal symptom cluster (t = 0.25, P = .802). In the CB group, the scores of all outcomes (all P < .05) decreased except for depression (t = 1.76, P = .095). CONCLUSION:The CB intervention is partially feasible and acceptable. It may also help to improve part of the symptom clusters of Chinese patients with GIT cancer undergoing chemotherapy. However, some modifications are needed in future studies to better test effectiveness. IMPLICATIONS FOR PRACTICE:Symptom management remains a major problem in clinical nursing. Such a CB intervention can be beneficial to the clinical management of symptom clusters. 10.1097/NCC.0000000000000625
    Real time remote symptom monitoring during chemotherapy for cancer: European multicentre randomised controlled trial (eSMART). Maguire Roma,McCann Lisa,Kotronoulas Grigorios,Kearney Nora,Ream Emma,Armes Jo,Patiraki Elisabeth,Furlong Eileen,Fox Patricia,Gaiger Alexander,McCrone Paul,Berg Geir,Miaskowski Christine,Cardone Antonella,Orr Dawn,Flowerday Adrian,Katsaragakis Stylianos,Darley Andrew,Lubowitzki Simone,Harris Jenny,Skene Simon,Miller Morven,Moore Margaret,Lewis Liane,DeSouza Nicosha,Donnan Peter T BMJ (Clinical research ed.) OBJECTIVE:To evaluate effects of remote monitoring of adjuvant chemotherapy related side effects via the Advanced Symptom Management System (ASyMS) on symptom burden, quality of life, supportive care needs, anxiety, self-efficacy, and work limitations. DESIGN:Multicentre, repeated measures, parallel group, evaluator masked, stratified randomised controlled trial. SETTING:Twelve cancer centres in Austria, Greece, Norway, Republic of Ireland, and UK. PARTICIPANTS:829 patients with non-metastatic breast cancer, colorectal cancer, Hodgkin's disease, or non-Hodgkin's lymphoma receiving first line adjuvant chemotherapy or chemotherapy for the first time in five years. INTERVENTION:Patients were randomised to ASyMS (intervention; n=415) or standard care (control; n=414) over six cycles of chemotherapy. MAIN OUTCOME MEASURES:The primary outcome was symptom burden (Memorial Symptom Assessment Scale; MSAS). Secondary outcomes were health related quality of life (Functional Assessment of Cancer Therapy-General; FACT-G), Supportive Care Needs Survey Short-Form (SCNS-SF34), State-Trait Anxiety Inventory-Revised (STAI-R), Communication and Attitudinal Self-Efficacy scale for cancer (CASE-Cancer), and work limitations questionnaire (WLQ). RESULTS:For the intervention group, symptom burden remained at pre-chemotherapy treatment levels, whereas controls reported an increase from cycle 1 onwards (least squares absolute mean difference -0.15, 95% confidence interval -0.19 to -0.12; P<0.001; Cohen's D effect size=0.5). Analysis of MSAS sub-domains indicated significant reductions in favour of ASyMS for global distress index (-0.21, -0.27 to -0.16; P<0.001), psychological symptoms (-0.16, -0.23 to -0.10; P<0.001), and physical symptoms (-0.21, -0.26 to -0.17; P<0.001). FACT-G scores were higher in the intervention group across all cycles (mean difference 4.06, 95% confidence interval 2.65 to 5.46; P<0.001), whereas mean scores for STAI-R trait (-1.15, -1.90 to -0.41; P=0.003) and STAI-R state anxiety (-1.13, -2.06 to -0.20; P=0.02) were lower. CASE-Cancer scores were higher in the intervention group (mean difference 0.81, 0.19 to 1.43; P=0.01), and most SCNS-SF34 domains were lower, including sexuality needs (-1.56, -3.11 to -0.01; P<0.05), patient care and support needs (-1.74, -3.31 to -0.16; P=0.03), and physical and daily living needs (-2.8, -5.0 to -0.6; P=0.01). Other SCNS-SF34 domains and WLQ were not significantly different. Safety of ASyMS was satisfactory. Neutropenic events were higher in the intervention group. CONCLUSIONS:Significant reduction in symptom burden supports the use of ASyMS for remote symptom monitoring in cancer care. A "medium" Cohen's effect size of 0.5 showed a sizable, positive clinical effect of ASyMS on patients' symptom experiences. Remote monitoring systems will be vital for future services, particularly with blended models of care delivery arising from the covid-19 pandemic. TRIAL REGISTRATION:Clinicaltrials.gov NCT02356081. 10.1136/bmj.n1647
    Symptom frequency and change of oldest old cancer patients. Pang Linda,de la Cruz Maxine,Wu Jimin,Liu Diane,Naqvi Mujtaba,Bruera Eduardo Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:The oldest old, described as those aged 85 and older, is a growing cancer population. There are limited studies evaluating the symptoms of the oldest old cancer patient population. Our study aimed to evaluate symptom frequency and clinical symptom change as assessed by the Edmonton Symptom Assessment System (ESAS) of the oldest old (≥ 85) compared to older adult (65-84) and general adult (18-64) outpatient cancer patients on initial consult and follow-up visit. METHODS:Retrospective review of a total of 441 patients, 200 randomly sampled patients in the general and older adult group and 41 consecutive patients in the oldest old group. Chart review was performed for demographic and clinical information including ESAS. RESULTS:The oldest old group had less advanced tumors and worse performance status and was receiving less cancer therapy. Eighty percent or more of these patients reported fatigue, sleep disturbance, appetite, and drowsiness. They experienced lower frequencies of pain (p < 0.0001), fatigue (p = 0.0338), nausea (p = 0.0151), feeling of well-being (p = 0.0245), sleep disturbance (p = 0.0484), financial distress (p = 0.0002), and spiritual distress (p = 0.0010) compared to the younger groups. Twenty-six to fifty-one percent of the oldest old patients' symptoms improved on the first follow-up visit. CONCLUSIONS:Oldest old cancer patients have high frequencies of multiple symptoms on initial referral. However, these symptom frequencies are lower when compared to younger age groups. Additionally, many of their symptoms improved on first follow-up visit in the palliative care clinic. More research is needed to address the needs of this growing cancer population and focus symptoms that can improve with palliative care intervention. 10.1007/s00520-019-04702-7
    Association of a Lay Health Worker Intervention With Symptom Burden, Survival, Health Care Use, and Total Costs Among Medicare Enrollees With Cancer. Patel Manali I,Ramirez David,Agajanian Richy,Agajanian Hilda,Coker Tumaini JAMA network open Importance:Undertreated patient symptoms require approaches that improve symptom burden. Objective:To determine the association of a lay health worker-led symptom screening and referral intervention with symptom burden, survival, health care use, and total costs among Medicare Advantage enrollees with a new diagnosis of solid or hematologic malignant neoplasms. Design, Setting, and Participants:This quality improvement study conducted at 9 community oncology practices from November 1, 2016, to October 31, 2018, compared newly diagnosed Medicare Advantage enrollees with solid or hematologic malignant neoplasms with patients diagnosed and treated 1 year prior. Analysis was conducted from August 1, 2019, to January 11, 2020. Interventions:Usual care augmented by a lay health worker trained to screen symptoms and refer patients to palliative care and behavioral medicine. Main Outcomes and Measures:The primary outcome was change in symptoms using the Edmonton Symptom Assessment Scale and the 9-item Patient Health Questionnaire at baseline and 6 and 12 months after enrollment. Secondary outcomes were between-group comparison of survival, 12-month health care use, and costs. Results:Among 425 patients in the intervention group and 407 patients in the control group, the mean (SD) age was 78.8 (8.3) years, 345 (41.5%) were female, and 407 (48.9%) were non-Hispanic white. Patients in the intervention group experienced a lower symptom burden as measured by the Edmonton Symptom Assessment Scale score over time compared with patients in the control group (mean [SD] difference, -1.9 [14.2]; 95% CI, -3.77 to -0.19; P = .01 for the intervention group and 2.32 [17.7]; 95% CI, 0.47 to 4.19; P = .02 for the control group). Similar findings were noted in 9-item Patient Health Questionnaire depression scores (mean [SD] difference, -0.63 [3.99]; 95% CI, -1.23 to -0.028; P = .04 for the intervention group and 1.67 [5.49]; 95% CI, 0.95 to 2.37; P = .01 for the control group). Patients in the intervention group compared with patients in the control group had fewer mean (SD) inpatient visits (0.54 [0.77]; 95% CI, 0.47-0.61 vs 0.72 [1.12]; 95% CI, 0.61-0.83; P = .04) and emergency department visits (0.43 [0.76]; 95% CI, 0.36-0.50 vs 0.57 [1.00]; 95% CI, 0.48-0.67; P = .002) per 1000 patients per year and lower total costs (median, $17 869 [interquartile range, $6865-$32 540] vs median, $18 473 [interquartile range, $6415-$37 910]; P = .02). A total of 180 patients in the intervention group and 189 patients in the control group died within 12 months. Among those who died, patients in the intervention group had greater hospice use (125 of 180 [69.4%] vs 79 of 189 [41.8%]; odds ratio, 3.16; 95% CI, 2.13-4.69; P < .001), fewer mean (SD) emergency department and hospital visits (emergency department: 0.10 [0.30]; 95% CI, 0.06-0.14 vs 0.30 [0.46]; 95% CI, 0.24-0.38; P = .001; hospital: 0.27 [0.44]; 95% CI, 0.21-0.34 vs 0.43 [0.82]; 95% CI, 0.32-0.55; P = .02), and lower costs (median, $3602 [interquartile range, $1076-$9436] vs median, $12 726 [interquartile range, $5259-$22 170]; P = .002), but there was no significant difference in inpatient deaths (18 of 180 [10.0%] vs 30 of 189 [15.9%]; P = .14). Conclusions and Relevance:This study suggests that a lay health worker-led intervention may be one way to improve burdensome and costly care. 10.1001/jamanetworkopen.2020.1023
    Symptom Experience, Management, and Outcomes According to Race and Social Determinants Including Genomics, Epigenomics, and Metabolomics (SEMOARS + GEM): an Explanatory Model for Breast Cancer Treatment Disparity. McCall Maura K,Connolly Mary,Nugent Bethany,Conley Yvette P,Bender Catherine M,Rosenzweig Margaret Q Journal of cancer education : the official journal of the American Association for Cancer Education Even after controlling for stage, comorbidity, age, and insurance status, black women with breast cancer (BC) in the USA have the lowest 5-year survival as compared with all other races for stage-matched disease. One potential cause of this survival difference is the disparity in cancer treatment, evident in many population clinical trials. Specifically, during BC chemotherapy, black women receive less relative dose intensity with more dose reductions and early chemotherapy cessation compared with white women. Symptom incidence, cancer-related distress, and ineffective communication, including the disparity in patient-centeredness of care surrounding patient symptom reporting and clinician assessment, are important factors contributing to racial disparity in dose reduction and early therapy termination. We present an evidence-based overview and an explanatory model for racial disparity in the symptom experience during BC chemotherapy that may lead to a reduction in dose intensity and a subsequent disparity in outcomes. This explanatory model, the Symptom Experience, Management, Outcomes and Adherence according to Race and Social determinants + Genomics Epigenomics and Metabolomics (SEMOARS + GEM), considers essential factors such as social determinants of health, clinician communication, symptoms and symptom management, genomics, epigenomics, and pharmacologic metabolism as contributory factors. 10.1007/s13187-019-01571-w
    Risk factors for clinician-reported symptom clusters in patients with advanced head and neck cancer in a phase 3 randomized clinical trial: RTOG 0129. Xiao Canhua,Hanlon Alexandra,Zhang Qiang,Movsas Benjamin,Ang Kian,Rosenthal David I,Nguyen-Tan P Félix,Kim Harold,Le Quynh,Bruner Deborah Watkins Cancer BACKGROUND:Chemoradiotherapy has become the standard of care for head and neck squamous cell carcinoma; however, those patients often experience multiple treatment-related symptoms or symptom clusters. Two symptom clusters have been identified for this population. Little is known about the risk factors of these symptom clusters. METHODS:Subjects comprised 684 patients who were treated with concurrent chemoradiotherapy in a phase 3 randomized clinical trial. This trial compared standard fractionation radiotherapy to accelerated fractionation radiotherapy. Symptom clusters were evaluated at the end of the first and the second cycle of chemotherapy, and 3 months after the start of radiotherapy. Mixed-effect modeling was used to observe risk factors for symptom clusters. RESULTS:Race and education were independent predictors for the head and neck cluster, whereas sex and history of tobacco use were independent predictors for the gastrointestinal cluster. Primary cancer site was only significant for the head and neck cluster when other factors were not controlled: patients with oropharyngeal cancer had more severe symptoms in the head and neck clusters than did patients with laryngeal cancer. In addition, patients receiving accelerated fractionation radiotherapy experienced more symptoms of radiomucositis, pain, and nausea at 3 months after the start of radiotherapy than those receiving standard fractionation radiotherapy. CONCLUSIONS:Demographic characteristics were more predictive to symptom clusters, whereas clinical characteristics, such as cancer site and treatment arms, were more significant for individual symptoms. Knowing the risk factors will enhance the capability of clinicians to evaluate patients' risk of severe symptom clusters and to personalize management strategies. 10.1002/cncr.28500
    Engaging high-risk groups in early lung cancer diagnosis: a qualitative study of symptom presentation and intervention preferences among the UK's most deprived communities. McCutchan Grace,Hiscock Julia,Hood Kerenza,Murchie Peter,Neal Richard D,Newton Gareth,Thomas Sara,Thomas Ann Maria,Brain Kate BMJ open OBJECTIVES:People at high-risk for lung cancer-current/former smokers, aged 40+ years, with serious lung comorbidity (ie, chronic obstructive pulmonary disease) and living in highly deprived areas-are more likely to delay symptom presentation. This qualitative study aimed to understand the influences on early presentation with lung cancer symptoms in high-risk individuals and intervention preferences. METHODS:Semi-structured qualitative interviews with 37 high-risk individuals (without a cancer diagnosis), identified through seven GP practices in socioeconomically deprived areas of England, Scotland and Wales (most deprived 20%). A symptom attribution task was used to explore lung symptom perception and help seeking, developed using Leventhal's Common Sense Model. Four focus groups with 16 high-risk individuals and 12 local stakeholders (healthcare professionals and community partners) were conducted to explore preferences for an intervention to promote early lung cancer symptom presentation. Data were synthesised using Framework analysis. RESULTS:Individual and area level indicators of deprivation confirmed that interview participants were highly deprived. Preoccupation with managing 'treatable' short-term conditions (chest infections), led to avoidance of acting on 'inevitable and incurable' long-term conditions (lung cancer). Feeling judged and unworthy of medical help because of their perceived social standing or lifestyle deterred medical help seeking, particularly when difficult life circumstances and traumatic events led to tobacco and alcohol addiction. . Participants recommended multifaceted interventions in community venues, with information about lung cancer symptoms and the benefits of early diagnosis, led by a trained and non-judgemental facilitator. CONCLUSIONS:This study was novel in engaging a high-risk population to gain an in-depth understanding of the broader contextual influences on lung cancer symptom presentation. Perceived lack of health service entitlement and complex lives facilitated avoidance of recognising and presenting with lung cancer symptoms. Community-based interventions have the potential to empower disadvantaged populations to seek medical help for lung symptoms. 10.1136/bmjopen-2018-025902
    Telephone interventions for symptom management in adults with cancer. Ream Emma,Hughes Amanda Euesden,Cox Anna,Skarparis Katy,Richardson Alison,Pedersen Vibe H,Wiseman Theresa,Forbes Angus,Bryant Andrew The Cochrane database of systematic reviews BACKGROUND:People with cancer experience a variety of symptoms as a result of their disease and the therapies involved in its management. Inadequate symptom management has implications for patient outcomes including functioning, psychological well-being, and quality of life (QoL). Attempts to reduce the incidence and severity of cancer symptoms have involved the development and testing of psycho-educational interventions to enhance patients' symptom self-management. With the trend for care to be provided nearer patients' homes, telephone-delivered psycho-educational interventions have evolved to provide support for the management of a range of cancer symptoms. Early indications suggest that these can reduce symptom severity and distress through enhanced symptom self-management. OBJECTIVES:To assess the effectiveness of telephone-delivered interventions for reducing symptoms associated with cancer and its treatment. To determine which symptoms are most responsive to telephone interventions. To determine whether certain configurations (e.g. with/without additional support such as face-to-face, printed or electronic resources) and duration/frequency of intervention calls mediate observed cancer symptom outcome effects. SEARCH METHODS:We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1); MEDLINE via OVID (1946 to January 2019); Embase via OVID (1980 to January 2019); (CINAHL) via Athens (1982 to January 2019); British Nursing Index (1984 to January 2019); and PsycINFO (1989 to January 2019). We searched conference proceedings to identify published abstracts, as well as SIGLE and trial registers for unpublished studies. We searched the reference lists of all included articles for additional relevant studies. Finally, we handsearched the following journals: Cancer, Journal of Clinical Oncology, Psycho-oncology, Cancer Practice, Cancer Nursing, Oncology Nursing Forum, Journal of Pain and Symptom Management, and Palliative Medicine. We restricted our search to publications published in English. SELECTION CRITERIA:We included randomised controlled trials (RCTs) and quasi-RCTs that compared one or more telephone interventions with one other, or with other types of interventions (e.g. a face-to-face intervention) and/or usual care, with the stated aim of addressing any physical or psychological symptoms of cancer and its treatment, which recruited adults (over 18 years) with a clinical diagnosis of cancer, regardless of tumour type, stage of cancer, type of treatment, and time of recruitment (e.g. before, during, or after treatment). DATA COLLECTION AND ANALYSIS:We used Cochrane methods for trial selection, data extraction and analysis. When possible, anxiety, depressive symptoms, fatigue, emotional distress, pain, uncertainty, sexually-related and lung cancer symptoms as well as secondary outcomes are reported as standardised mean differences (SMDs) with 95% confidence intervals (CIs), and we presented a descriptive synthesis of study findings. We reported on findings according to symptoms addressed and intervention types (e.g. telephone only, telephone combined with other elements). As many studies included small samples, and because baseline scores for study outcomes often varied for intervention and control groups, we used change scores and associated standard deviations. The certainty of the evidence for each outcome was interpreted using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS:Thirty-two studies were eligible for inclusion; most had moderate risk of bias,often related to blinding. Collectively, researchers recruited 6250 people and studied interventions in people with a variety of cancer types and across the disease trajectory, although many participants had breast cancer or early-stage cancer and/or were starting treatment. Studies measured symptoms of anxiety, depression, emotional distress, uncertainty, fatigue, and pain, as well as sexually-related symptoms and general symptom intensity and/or distress. Interventions were primarily delivered by nurses (n = 24), most of whom (n = 16) had a background in oncology, research, or psychiatry. Ten interventions were delivered solely by telephone; the rest combined telephone with additional elements (i.e. face-to-face consultations and digital/online/printed resources). The number of calls delivered ranged from 1 to 18; most interventions provided three or four calls. Twenty-one studies provided evidence on effectiveness of telephone-delivered interventions and the majority appeared to reduce symptoms of depression compared to control. Nine studies contributed quantitative change scores (CSs) and associated standard deviation results (or these could be calculated). Likewise, many telephone interventions appeared effective when compared to control in reducing anxiety (16 studies; 5 contributed quantitative CS results); fatigue (9 studies; 6 contributed to quantitative CS results); and emotional distress (7 studies; 5 contributed quantitative CS results). Due to significant clinical heterogeneity with regards to interventions introduced, study participants recruited, and outcomes measured, meta-analysis was not conducted. For other symptoms (uncertainty, pain, sexually-related symptoms, dyspnoea, and general symptom experience), evidence was limited; similarly meta-analysis was not possible, and results from individual studies were largely conflicting, making conclusions about their management through telephone-delivered interventions difficult to draw. Heterogeneity was considerable across all trials for all outcomes. Overall, the certainty of evidence was very low for all outcomes in the review. Outcomes were all downgraded due to concerns about overall risk of bias profiles being frequently unclear, uncertainty in effect estimates and due to some inconsistencies in results and general heterogeneity. Unsubstantiated evidence suggests that telephone interventions in some capacity may have a place in symptom management for adults with cancer. However, in the absence of reliable and homogeneous evidence, caution is needed in interpreting the narrative synthesis. Further, there were no clear patterns across studies regarding which forms of interventions (telephone alone versus augmented with other elements) are most effective. It is impossible to conclude with any certainty which forms of telephone intervention are most effective in managing the range of cancer-related symptoms that people with cancer experience. AUTHORS' CONCLUSIONS:Telephone interventions provide a convenient way of supporting self-management of cancer-related symptoms for adults with cancer. These interventions are becoming more important with the shift of care closer to patients' homes, the need for resource/cost containment, and the potential for voluntary sector providers to deliver healthcare interventions. Some evidence supports the use of telephone-delivered interventions for symptom management for adults with cancer; most evidence relates to four commonly experienced symptoms - depression, anxiety, emotional distress, and fatigue. Some telephone-delivered interventions were augmented by combining them with face-to-face meetings and provision of printed or digital materials. Review authors were unable to determine whether telephone alone or in combination with other elements provides optimal reduction in symptoms; it appears most likely that this will vary by symptom. It is noteworthy that, despite the potential for telephone interventions to deliver cost savings, none of the studies reviewed included any form of health economic evaluation. Further robust and adequately reported trials are needed across all cancer-related symptoms, as the certainty of evidence generated in studies within this review was very low, and reporting was of variable quality. Researchers must strive to reduce variability between studies in the future. Studies in this review are characterised by clinical and methodological diversity; the level of this diversity hindered comparison across studies. At the very least, efforts should be made to standardise outcome measures. Finally, studies were compromised by inclusion of small samples, inadequate concealment of group allocation, lack of observer blinding, and short length of follow-up. Consequently, conclusions related to symptoms most amenable to management by telephone-delivered interventions are tentative. 10.1002/14651858.CD007568.pub2
    Cancer symptom awareness in the US: Sociodemographic differences in a population-based survey of adults. Sarma Elizabeth A,Rendle Katharine A,Kobrin Sarah C Preventive medicine Symptom awareness may improve cancer outcomes by prompting timely help-seeking and diagnosis. Research in the UK has shown lower symptom awareness among sociodemographic groups at higher risk of poor cancer outcomes; however, no population-based surveys in the US have assessed whether cancer symptom awareness varies across sociodemographic groups. We therefore examined associations between sociodemographic factors and recognition of 11 cancer symptoms using a novel population-based survey of US adults. We conducted telephone interviews in 2014 with a population-representative sample of English-speaking adults (aged 50 and older) in the US (N = 1425) using an adapted Awareness and Beliefs about Cancer (ABC) survey. Socioeconomic status (SES) was indexed by education. Additional sociodemographic factors included gender, age, marital status, and race. We used multivariable logistic regression models to examine the association between sociodemographic factors and recognition of each symptom, adjusting for cancer experience. Participants recognized an average of 8.43 symptoms as potential signs of cancer. In multivariable analyses, less education consistently predicted lower recognition across the symptoms. As socioeconomic inequalities in cancer mortality widen, it is increasingly important to understand factors that may contribute to these disparities. Our results suggest that US adults of lower SES have lower cancer symptom awareness across symptoms, findings that echo results from other developed countries. With low rates of cancer screening, another approach to reducing cancer burden and disparities may be through greater symptom awareness for symptoms with lower awareness, though additional work is needed to identify mechanisms through which awareness may have its effects on cancer outcomes. 10.1016/j.ypmed.2020.106005
    [Effects of oxidative stress on cognitive impairment in first episode schizophrenia]. Wang Y P,Zhang P F,Yuan X X,Liu Y F,Li H H,Tao Q,Li X,Pang L J,Song X Q Zhonghua yi xue za zhi To observe the relationship between serum oxidative stress as well as brain-derived neurotrophic factor (BDNF) and cognitive function in first-episode drug-free schizophrenics, and to explore the possible effect of oxidative stress in cognitive impairment of first-episode schizophrenia. A total of 125 first-episode drug-free schizophrenics (schizophrenia group) from the First Affiliated Hospital of Zhengzhou University and 80 healthy individuals (control group) were enrolled. The serum concentration of oxidized glutathione (GSSG) was measured by the Microenzyme method the serum concentration of nitric oxide (NO) was measured by one-step method, the BDNF level was measured by enzyme linked immunosorbent assay and Matrics Consensus Cognitive Battery(MCCB) was used to evaluate the cognitive function. (1)The serum level of BDNF in schizophrenia group (2 763±1 728 pg/ml) was significantly lower than that in control group (4 165±1 299 pg/ml)(0.001). And the serum levels of GSSG and NO in schizophrenia group ((36±9), (81±65) μmol/L) were significantly higher than that in control group ((27±11), (24±16) μmol/L) (0.001). In comparison with the control group scores were significantly lower in the seven domains of cognitive function in the schizophrenia group (all 0.001). (2)After controlling the confounding factors like age, gender, cultural differences and course of disease by partial correlation analysis, the correlation analysis showed that: serum level of BDNF in schizophrenia group had positive correlation with Information processing rate T points, attentional facilitating T points, working memory T points and Reasoning and problem solving T points (0.417, 0.206, 0.247, 0.318, all 0.05). In schizophrenia group the serum level of GSSG had a negative correlation with information processing rate T points and reasoning and problem solving T points (-0.321, -0.231, all 0.05). The serum level of NO was negatively related to Information processing rate T points working memory T points Verbal learning T points(-0.201, -0.193, -0.237, all 0.05). Oxidative stress may be involved in the cognitive impairment of schizophrenia Oxidation products are risk factors for cognitive impairment of schizophrenia and BDNF is a protective factor of cognitive function. 10.3760/cma.j.issn.0376-2491.2019.01.003
    Deferoxamine regulates neuroinflammation and oxidative stress in rats with diabetes-induced cognitive dysfunction. Zeinivand Motahareh,Nahavandi Arezo,Zare Mahdie Inflammopharmacology Diabetic encephalopathy, a major complication of diabetes, is characterized by cognitive impairment and structural and neurochemical abnormalities. Neuroinflammation following impairment of iron homeostasis is a remarkable feature of several neurological disorders. In the present study, we investigated the role of deferoxamine (DFO), as a clinical iron chelator, in improvement of type 1 diabetes-induced cognitive dysfunction. Streptozotocin was utilized to induce type 1 diabetic in rat model. Animals were categorized into four groups: control, diabetic, diabetic + Iron and diabetic + DFO. Hence, DFO was administered at a dose of 100 mg/kg S.C and iron was administered at a dose of 12 mg/kg P.O for 8 weeks. Finally, Y-maze and passive avoidance were performed. Measurement of IL-6, ferritin, and the brain-derived neurotrophic factor (BDNF) expression was carried out using ELISA. Our results showed significant increased levels of ferritin (P < 0.001), IL-6 (P < 0.001), MDA (P < 0.01), as well as decreased levels of BDNF (P < 0.001) in the diabetic and iron groups compared to control. Post-treatment with DFO for 8 weeks after the induction of diabetes, markedly reduced levels of ferritin (P < 0.001), IL-6 (P < 0.01), and MDA (P < 0.001), as well as increased levels of BDNF (P < 0.01) compared to the diabetic and iron groups was observed. Collectively, these findings demonstrate the validity of DFO as a good candidate to attenuate cognitive dysfunction following diabetes by targeting oxidative stress, neuroinflammation, and modulation of iron homeostasis. 10.1007/s10787-019-00665-7
    Oxidative stress-induced cognitive impairment in obesity can be reversed by vitamin D administration in rats. Hajiluian Ghazaleh,Abbasalizad Farhangi Mahdieh,Nameni Ghazaleh,Shahabi Parviz,Megari-Abbasi Mehran Nutritional neuroscience BACKGROUND:There is evidence that obesity leads to cognitive impairments via several markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase and malondialdehyde (MDA) in the hippocampus. Increased inflammatory markers in the brain have obesity triggering effects. In the current study we aimed to investigate the effects of vitamin D on cognitive function, nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α concentration and markers of oxidative stress in the hippocampus of high-fat diet-induced obese rats. METHODS AND MATERIALS:Forty male Wistar rats were divided into two groups: control diet (CD) and high-fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: CD, CD + vitamin D, HFD and HFD + vitamin D. Vitamin D was administered at 500 IU/kg dosage for 5 weeks. Four weeks after supplementation, Morris water maze test was performed. NF-κB and TNF-α concentration in the hippocampus were determined using ELISA kits. Moreover, oxidative stress markers in the hippocampus including GPx, SOD, MDA and CAT concentrations were measured by spectrophotometry methods. RESULTS:HFD significantly increased TNF-α (P = 0.04) and NF-κB (P = 0.01) concentrations in the hippocampus compared with CD. Vitamin D treatment led to a significant reduction in hippocampus NF-κB concentrations in HFD + vitamin D group (P = 0.001); however, vitamin D had no effect on TNF-α concentrations. Moreover, HFD significantly induced oxidative stress by reducing GPx, SOD and increasing MDA concentrations in the hippocampus. Vitamin D supplementation in HFD group also significantly increased GPx, SOD and reduced MDA concentrations. CONCLUSION:Vitamin D improved hippocampus oxidative stress and inflammatory markers in HFD-induced obese rats and improved cognitive performance. Further studies are needed to better clarify the underlying mechanisms. 10.1080/1028415X.2017.1348436
    The Role of Oxidative Stress in Etiopathogenesis of Chemotherapy Induced Cognitive Impairment (CICI)-"Chemobrain". Gaman Amelia Maria,Uzoni Adriana,Popa-Wagner Aurel,Andrei Anghel,Petcu Eugen-Bogdan Aging and disease Chemobrain or chemotherapy induced cognitive impairment (CICI) represents a new clinical syndrome characterised by memory, learning and motor function impairment. As numerous patients with cancer are long-term survivors, CICI represent a significant factor which may interfere with their quality of life. However, this entity CICI must be distinguished from other cognitive syndromes and addressed accordingly. At the present time, experimental and clinical research suggests that CICI could be induced by numerous factors including oxidative stress. This type of CNS injury has been previously described in cancer patients treated with common anti-neoplastic drugs such as doxorubicine, carmustine, methotrexate and cyclophosphamide. It seems that all these pharmacological factors promote neuronal death through a final common pathway represented by TNF alpha (tumour necrosis factor). However, as cancer in general is diagnosed more commonly in the aging population, the elderly oncological patient must be treated with great care since aging per se is also impacted by oxidative stress and potentiually by TNF alpha deleterious action on brain parenchyma. In this context, some patients may develop cognitive dysfunction well before the appearance of CICI. In addition, chemotherapy may worsen their cognitive function. Therefore, at the present time, there is an acute need for development of effective therapeutic methods to prevent CICI as well as new methods of early CICI diagnosis. 10.14336/AD.2015.1022
    Plausible biochemical mechanisms of chemotherapy-induced cognitive impairment ("chemobrain"), a condition that significantly impairs the quality of life of many cancer survivors. Ren Xiaojia,Boriero Diana,Chaiswing Luksana,Bondada Subbarao,St Clair Daret K,Butterfield D Allan Biochimica et biophysica acta. Molecular basis of disease Increasing numbers of cancer patients survive and live longer than five years after therapy, but very often side effects of cancer treatment arise at same time. One of the side effects, chemotherapy-induced cognitive impairment (CICI), also called "chemobrain" or "chemofog" by patients, brings enormous challenges to cancer survivors following successful chemotherapeutic treatment. Decreased abilities of learning, memory, attention, executive function and processing speed in cancer survivors with CICI, are some of the challenges that greatly impair survivors' quality of life. The molecular mechanisms of CICI involve very complicated processes, which have been the subject of investigation over the past decades. Many mechanistic candidates have been studied including disruption of the blood-brain barrier (BBB), DNA damage, telomere shortening, oxidative stress and associated inflammatory response, gene polymorphism of neural repair, altered neurotransmission, and hormone changes. Oxidative stress is considered as a vital mechanism, since over 50% of FDA-approved anti-cancer drugs can generate reactive oxygen species (ROS) or reactive nitrogen species (RNS), which lead to neuronal death. In this review paper, we discuss these important candidate mechanisms, in particular oxidative stress and the cytokine, TNF-alpha and their potential roles in CICI. 10.1016/j.bbadis.2019.02.007
    Chemotherapy-Induced Cognitive Impairment Is Associated with Increased Inflammation and Oxidative Damage in the Hippocampus. Bagnall-Moreau Ciara,Chaudhry Sovira,Salas-Ramirez Kaliris,Ahles Tim,Hubbard Karen Molecular neurobiology Increasing evidence indicates that chemotherapy results in long-term effects on cognitive dysfunction in some cancer survivors. While many studies have established the domains of cognition and corresponding regions in the brain most affected, little is revealed about the potential molecular mechanisms that mediate these adverse changes after treatment. The effects of chemotherapy on the brain are likely attributed to various mechanisms, including oxidative stress and immune dysregulation, features that are also reminiscent of cognitive aging. We have investigated the cognitive effects of a cocktail composed of doxorubicin and cyclophosphamide (AC-chemo) in a surgical ovariectomized rodent model. In this study, we address whether the levels of pro-inflammatory cytokines and oxidative stress-responsive gene markers are altered in the CNS of rats treated with systemic AC-chemo. We further evaluated the levels of nucleic acids modified by oxidative stress in the hippocampus using both immunohistochemical and Northern blotting techniques with a monoclonal antibody against 8-hydroxyguanosine (8-OHG) and 8-OHdG base lesions. We demonstrate that ERK 1/2 and JNK/SAPK signaling activities are elevated in the hippocampus of AC-chemo rats. The levels of pro-inflammatory, oxidative stress-responsive, and RNA/DNA damage markers were also higher in drug-injected animals relative to saline controls. The results indicate that the effects of AC chemotherapy are associated with oxidative damage and a global stress response in the hippocampus. These alterations in the molecular signature of the brain may underlie the processes that contribute to cognitive impairment after treatment. 10.1007/s12035-019-1589-z
    Chemotherapy-induced cognitive impairment: focus on the intersection of oxidative stress and TNFα. Rummel Nicole G,Chaiswing Luksana,Bondada Subbarao,St Clair Daret K,Butterfield D Allan Cellular and molecular life sciences : CMLS Chemotherapy-induced cognitive impairment (CICI) has been observed in a large fraction of cancer survivors. Although many of the chemotherapeutic drugs do not cross the blood-brain barrier, following treatment, the structure and function of the brain are altered and cognitive dysfunction occurs in a significant number of cancer survivors. The means by which CICI occurs is becoming better understood, but there still remain unsolved questions of the mechanisms involved. The hypotheses to explain CICI are numerous. More than 50% of FDA-approved cancer chemotherapy agents are associated with reactive oxygen species (ROS) that lead to oxidative stress and activate a myriad of pathways as well as inhibit pathways necessary for proper brain function. Oxidative stress triggers the activation of different proteins, one in particular is tumor necrosis factor alpha (TNFα). Following treatment with various chemotherapy agents, this pro-inflammatory cytokine binds to its receptors at the blood-brain barrier and translocates to the parenchyma via receptor-mediated endocytosis. Once in brain, TNFα initiates pathways that may eventually lead to neuronal death and ultimately cognitive impairment. TNFα activation of the c-jun N-terminal kinases (JNK) and Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathways may contribute to both memory decline and loss of higher executive functions reported in patients after chemotherapy treatment. Chemotherapy also affects the brain's antioxidant capacity, allowing for accumulation of ROS. This review expands on these topics to provide insights into the possible mechanisms by which the intersection of oxidative stress and TNFΑ are involved in chemotherapy-induced cognitive impairment. 10.1007/s00018-021-03925-4
    C-phycocyanin Mitigates Cognitive Impairment in Doxorubicin-Induced Chemobrain: Impact on Neuroinflammation, Oxidative Stress, and Brain Mitochondrial and Synaptic Alterations. Wang Chenying,Zhao Yuhang,Wang Lewei,Pan Shunji,Liu Yumei,Li Sanqiang,Wang Dongmei Neurochemical research Chemotherapy-induced cognitive impairment (CICI) is a common detrimental effect of cancer treatment, occurring in up to 75% of cancer patients. The widely utilized chemotherapeutic agent doxorubicin (DOX) has been implicated in cognitive decline, mostly via cytokine-induced neuroinflammatory and oxidative and mitochondrial damage to brain tissues. C-phycocyanin (CP) has previously been shown to have potent anti-inflammatory, antioxidant, and mitochondrial protective properties. Therefore, this present study was aimed to investigate the neuroprotective effects of CP against DOX-elicited cognitive impairment and explore the underlying mechanisms. CP treatment (50 mg/kg) significantly improved behavioral deficits in DOX-treated mice. Furthermore, CP suppressed DOX-induced neuroinflammation and oxidative stress, mitigated mitochondrial abnormalities, rescued dendritic spine loss, and increased synaptic density in the hippocampus of DOX-treated mice. Our results suggested that CP improves established DOX-induced cognitive deficits, which could be explained at least partly by inhibition of neuroinflammatory and oxidant stress and attenuation of mitochondrial and synaptic dysfunction. 10.1007/s11064-020-03164-2
    Nomogram-based parameters to predict overall survival in a real-world advanced cancer population undergoing palliative care. Zhao Weiwei,He Zhiyong,Li Yintao,Jia Huixun,Chen Menglei,Gu Xiaoli,Liu Minghui,Zhang Zhe,Wu Zhenyu,Cheng Wenwu BMC palliative care BACKGROUND:Although palliative care has been accepted throughout the cancer trajectory, accurate survival prediction for advanced cancer patients is still a challenge. The aim of this study is to identify pre-palliative care predictors and develop a prognostic nomogram for overall survival (OS) in mixed advanced cancer patients. METHODS:A total of 378 consecutive advanced cancer patients were retrospectively recruited from July 2013 to October 2015 in one palliative care unit in China. Twenty-three clinical and laboratory characters were collected for analysis. Prognostic factors were identified to construct a nomogram in a training cohort (n = 247) and validated in a testing cohort (n = 131) from the setting. RESULTS:The median survival time was 48.0 (95% CI: 38.1-57.9) days for the training cohort and 52.0 (95% CI: 34.6-69.3) days for the validation cohort. Among pre-palliative care factors, sex, age, tumor stage, Karnofsky performance status, neutrophil count, hemoglobin, lactate dehydrogenase, albumin, uric acid, and cystatin-C were identified as independent prognostic factors for OS. Based on the 10 factors, an easily obtained nomogram predicting 90-day probability of mortality was developed. The predictive nomogram had good discrimination and calibration, with a high C-index of 0.76 (95% CI: 0.73-0.80) in the development set. The strong discriminative ability was externally conformed in the validation cohort with a C-index of 0.75. CONCLUSIONS:A validated prognostic nomogram has been developed to quantify the risk of mortality for advanced cancer patients undergoing palliative care. This tool may be useful in optimizing therapeutic approaches and preparing for clinical courses individually. 10.1186/s12904-019-0432-7
    Reducing Cancer Costs Through Symptom Management and Triage Pathways. Barkley Ronald,Soobader Mah-Jabeen,Wang Jun,Blau Sibel,Page Ray D Journal of oncology practice PURPOSE:Value-based care infers care that is high quality at a comparatively low total cost. A key strategy for value-based oncology care is to avoid unnecessary emergency room (ER) visits and associated hospitalizations of patients receiving treatment for cancer. Early experience with this strategy showed that symptom management in patients with cancer can result in the reduction of ER events and hospitalizations. However, quantifying the actual savings achieved has been elusive. In this article, we present the impact of symptom management and triage pathways programs deployed at two midsize community oncology practices. We then quantify the actual dollar saving in their Medicare and commercial populations. METHODS:Symptom management records generated through the ER triage programs at the two practices were screened to identify avoided ER events. This approach was validated with an independent analysis using Medicare claim data from the Oncology Care Model program in which both practices participate. Bootstrap simulations were used to test for statistical significance of the ER event rate changes before and after the launch of the program. Average event and annual total cost savings from avoided ER incidents and ER-related hospitalizations were then calculated. RESULTS:Two hundred twenty-two avoided ER events were identified, for an estimated net annualized savings generated by the two practices of $3.85 million. Although the ER rate reduction was not statistically significant, these findings are consistent with the observed reduction of ER event rates among a subset of Oncology Care Model beneficiaries at the two practices. CONCLUSION:ER events and associated hospitalizations can be avoided as well as quantified as a result of the deployment of a practice-level integrated platform that incorporates physician-scripted symptom management protocols and telephone triage pathways. 10.1200/JOP.18.00082
    Palliative Care and the Management of Common Distressing Symptoms in Advanced Cancer: Pain, Breathlessness, Nausea and Vomiting, and Fatigue. Henson Lesley A,Maddocks Matthew,Evans Catherine,Davidson Martin,Hicks Stephanie,Higginson Irene J Journal of clinical oncology : official journal of the American Society of Clinical Oncology Good symptom management in oncology is associated with improved patient and family quality of life, greater treatment compliance, and may even offer survival advantages. With population growth and aging, the proportion of patients with multiple symptoms-both related and unrelated to their cancer-is anticipated to increase, supporting calls for a more routine and integrated approach to symptom management. This article presents a summary of the literature for the use of symptom assessment tools and reviews the management of four common and distressing symptoms commonly experienced by people with advanced cancer: pain, breathlessness, nausea and vomiting, and fatigue. We also discuss the role of palliative care in supporting a holistic approach to symptom management throughout the cancer trajectory. 10.1200/JCO.19.00470
    Polysymptomatology in Pediatric Patients Receiving Palliative Care Based on Parent-Reported Data. Feudtner Chris,Nye Russell,Hill Douglas L,Hall Matt,Hinds Pam,Johnston Emily E,Friebert Sarah,Hays Ross,Kang Tammy I,Wolfe Joanne, JAMA network open Importance:Pediatric palliative care treats patients with a wide variety of advanced illness conditions, often with substantial levels of pain and other symptoms. Clinical and research advancements regarding symptom management for these patients are hampered by the scarcity of data on symptoms as well as an overreliance on clinician report. Objective:To provide a detailed description of the symptoms among patients receiving pediatric palliative care based on parental report via a validated, structured symptom assessment measure. Design, Setting, and Participants:Baseline data for this cross-sectional analysis were collected between April 10, 2017, and February 5, 2020, from pediatric palliative care programs in 7 children's hospitals located in Akron, Ohio; Boston, Massachusetts; Birmingham, Alabama; Houston, Texas; Minneapolis, Minnesota; Philadelphia, Pennsylvania; and Seattle, Washington. Data were collected in the hospital, outpatient, and home setting from patients 30 years of age or younger who were receiving pediatric palliative care at 1 of the study sites. Exposures:Analyses were stratified by patients' demographic characteristics, including age, and by whether the patients had received a diagnosis of any of 10 non-mutually exclusive complex chronic condition categories. Main Outcomes and Measures:Twenty symptoms measured via the modified Memorial Symptom Assessment Scale, which scores the frequency and severity of any symptom that is present and provides a total symptom score. Results:Among the first 501 patients enrolled, the median age was 4.1 years (interquartile range, 0.8-12.9 years), 267 (53.3%) were male, and 356 (71.1%) were White. The most prevalent complex chronic conditions included gastrointestinal (357 [71.3%]), neurologic (289 [57.7%]), and cardiovascular (310 [61.9%]) conditions; 438 patients (87.4%) were technology dependent. Parents reported a mean (SD) of 6.7 (3.4) symptoms per patient and a median of 7 symptoms (interquartile range, 4-9 symptoms). A total of 367 patients (73.3%) had 5 or more symptoms. The 5 most prevalent symptoms were pain (319 [63.7%]; 95% CI, 59.4%-67.8%), lack of energy (295 [58.9%]; 95% CI, 54.5%-63.1%), irritability (280 [55.9%]; 95% CI, 51.5%-60.2%), drowsiness (247 [49.3%]; 95% CI, 44.9%-53.7%), and shortness of breath (232 [46.3%]; 95% CI, 41.9%-50.7%). Although older patients were reported by parents as having experienced more symptoms and having higher total symptom scores, variation across condition categories was relatively minor. Patients in the upper 10th percentile of total symptom scores had a median of 12.0 symptoms (interquartile range, 11-13). Conclusions and Relevance:In this cross-sectional study, most children receiving palliative care were experiencing polysymptomatology. An important subgroup of patients frequently experienced numerous severe symptoms. Assessment and management of patients with polysymptomatology are critical aspects of pediatric palliative care. 10.1001/jamanetworkopen.2021.19730
    Web and mobile-based symptom management interventions for physical symptoms of people with advanced cancer: A systematic review and meta-analysis. Saeidzadeh Seyedehtanaz,Kamalumpundi Vijayvardhan,Chi Nai-Ching,Nair Rajeshwari,Gilbertson-White Stephanie Palliative medicine BACKGROUND:Symptom management is a critical aspect of comprehensive palliative care for people with advanced cancer. Web and mobile-based applications are promising e-Health modalities that can facilitate timely access to symptom management interventions for this population. AIM:To evaluate the efficacy of web and mobile-based symptom management interventions in alleviating physical symptom burden in people with advanced cancer. DESIGN:A systematic review and meta-analysis was conducted. PROSPERO ID = CRD42020155295. DATA SOURCES:We searched databases including PubMed, PsycINFO, and CINAHL from 1991 until 2019. Inclusion criteria were: adults with advanced cancer, web or mobile-based interventions targeting symptom management, and report of physical symptom data. Risk of bias was assessed using the ROBINS-I and RoB2. Using RevMan, standardized mean difference (SMD) and 95% confidence intervals were calculated. Heterogeneity was assessed using the statistic. An assessment of interventions was conducted by evaluating the delivery mode, duration, and evaluation of application feature and theoretical elements. RESULTS:A total of 19 studies are included in the systematic review and 18 in the meta-analysis. Majority of the studies were deemed to have high risk of bias. Most of the interventions used a web-application for delivering their education ( = 17). While the interventions varied regarding duration and content, they were mainly guided by a symptom management theory. Web and mobile-based interventions significantly improved the overall physical symptom burden (SMD = -0.18; 95% CI = -0.28 to -0.09;  = 0%;  = 0.0002). CONCLUSIONS:Web and mobile-based intervention are efficacious in decreasing the overall physical symptom burden in people with advanced cancer. 10.1177/02692163211006317
    Vitamin C alleviates LPS-induced cognitive impairment in mice by suppressing neuroinflammation and oxidative stress. Zhang Xiao-Ying,Xu Zhi-Peng,Wang Wei,Cao Jiang-Bei,Fu Qiang,Zhao Wei-Xing,Li Yang,Huo Xiu-Lin,Zhang Li-Ming,Li Yun-Feng,Mi Wei-Dong International immunopharmacology Neuroinflammation is believed to be one of the primary causes of cognitive impairment. Previous studies showed that the antioxidant vitamin C (Vit C) performs many beneficial functions such as immunostimulant and anti-inflammatory actions, but its role in inflammatory cognitive impairment is unclear. In the current study, we investigated the effect and possible mechanism of action of Vit C in lipopolysaccharide (LPS)-induced cognitive impairment. Intracerebroventricular LPS-induced memory impairment was used as the model for neuroinflammatory cognitive dysfunction. Vit C was administered by intracerebroventricular microinjection 30 min prior to LPS exposure. It was found that Vit C significantly protected animals from LPS-induced memory impairment as evidenced by improved performance in the Morris water maze and novel object recognition tests without changes in spontaneous locomotor activity. Vit C pretreatment inhibited the activation of microglia and the production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Furthermore, Vit C pretreatment markedly decreased the malondialdehyde (MDA) level, increased superoxide dismutase (SOD) activity, and modulated the Bax/Bcl-2 ratio and p-p38 MAPK activation in the hippocampus of LPS-treated mice. Together, these results suggest that vitamin C pretreatment could protect mice from LPS-induced cognitive impairment, possibly through the modulation of oxidative stress and inflammatory responses. 10.1016/j.intimp.2018.10.020
    Association of Cerebrospinal Fluid Neurofilament Light Protein With Risk of Mild Cognitive Impairment Among Individuals Without Cognitive Impairment. Kern Silke,Syrjanen Jeremy A,Blennow Kaj,Zetterberg Henrik,Skoog Ingmar,Waern Margda,Hagen Clinton E,van Harten Argonde C,Knopman David S,Jack Clifford R,Petersen Ronald C,Mielke Michelle M JAMA neurology Importance:Accumulating data suggest that elevated cerebrospinal fluid (CSF) neurofilament light (NfL) and neurogranin (Ng) levels are associated with cognitive decline and may be useful markers of neurodegeneration. However, to our knowledge, previous studies have not assessed these CSF markers in the community, evaluated them with regards to risk of mild cognitive impairment (MCI), or compared their prognostic value with CSF total tau (T-tau) or phosphorylated tau (P-tau). Objective:To determine (1) whether CSF NfL and Ng levels were associated with risk of MCI, (2) the effect size of these markers compared with CSF T-tau or P-tau for risk of MCI, and (3) whether CSF amyloid-β (Aβ42) modified these associations. Design, Setting and Participants:The analyses included 648 participants without cognitive impairment who were enrolled into the prospective population-based Mayo Clinic Study of Aging between January 2004 and December 2015 with available CSF data and at least 1 follow-up visit. Participants were followed up for a median of 3.8 years (interquartile range, 2.6-5.4 years). The CSF NfL and Ng levels were measured using an in-house sandwich enzyme-linked immunosorbent assay. The CSF Aβ42, T-tau, and P-tau levels were measured with automated electrochemiluminescence immunoassays. Cox proportional hazards models, with age as the timescale, were used to assess the association between CSF NfL, Ng, Aβ42, T-tau, or P-tau with risk of MCI after adjusting for sex, education, apolipoprotein E genotype, and the Charlson comorbidity index. To examine CSF Aβ42 as an effect modifier, it was categorized into tertiles; the bottom tertile was defined as having elevated brain amyloid. Main Outcomes and Measures:Risk of MCI. Results:At baseline, the median age of the 648 participants without cognitive impairment was 72.3 years (range, 50.7-95.3 years) and 366 (56.5%) were men; 96 (14.8%) developed incident MCI. Compared with the bottom quartile, the top quartile of CSF NfL was associated with a 3.1-fold increased risk of MCI (hazard ratio, 3.13; 95% CI, 1.36-7.18) in multivariate models. Neither CSF T-tau, P-tau, nor Ng was associated with risk of MCI. There was no interaction between Aβ42 and CSF NfL for risk of MCI. Conclusions and Relevance:Elevated CSF NfL levels but not CSF T-tau, P-tau or Ng are a risk factor for MCI in a community population and are independent of brain amyloid. 10.1001/jamaneurol.2018.3459
    Profile of cognitive impairment and underlying pathology in multiple system atrophy. Koga Shunsuke,Parks Adam,Uitti Ryan J,van Gerpen Jay A,Cheshire William P,Wszolek Zbigniew K,Dickson Dennis W Movement disorders : official journal of the Movement Disorder Society BACKGROUND:The objectives of this study were to elucidate any potential association between α-synuclein pathology and cognitive impairment and to determine the profile of cognitive impairment in multiple system atrophy (MSA) patients. To do this, we analyzed the clinical and pathologic features in autopsy-confirmed MSA patients. METHODS:We retrospectively reviewed medical records, including neuropsychological test data, in 102 patients with autopsy-confirmed MSA in the Mayo Clinic brain bank. The burden of glial cytoplasmic inclusions and neuronal cytoplasmic inclusions were semiquantitatively scored in the limbic regions and middle frontal gyrus. We also assessed concurrent pathologies potentially causing dementia including Alzheimer's disease, hippocampal sclerosis, and cerebrovascular pathology. RESULTS:Of 102 patients, 33 (32%) were documented to have cognitive impairment. Those that received objective testing, deficits primarily in processing speed and attention/executive functions were identified, which suggests a frontal-subcortical pattern of dysfunction. Of these 33 patients with cognitive impairment, 8 patients had concurrent pathologies of dementia. MSA patients with cognitive impairment had a greater burden of neuronal cytoplasmic inclusions in the dentate gyrus than patients without cognitive impairment, both including and excluding patients with concurrent pathologies of dementia. CONCLUSIONS:The cognitive deficits observed in this study were more evident on neuropsychological assessment than with cognitive screens. Based on these findings, we recommend that clinicians consider more in-depth neuropsychological assessments if patients with MSA present with cognitive complaints. Although we did not identify the correlation between cognitive deficits and responsible neuroanatomical regions, a greater burden of neuronal cytoplasmic inclusions in the limbic regions was associated with cognitive impairment in MSA. © 2016 International Parkinson and Movement Disorder Society. 10.1002/mds.26874
    Chronic acrylamide exposure induced glia cell activation, NLRP3 infl-ammasome upregulation and cognitive impairment. Liu Ying,Zhang Xing,Yan Dandan,Wang Yiqi,Wang Na,Liu Yufan,Tan Aijun,Chen Xiaoyi,Yan Hong Toxicology and applied pharmacology Acrylamide (ACR), a potential neurotoxin, is present in diet and drinking water. Dietary exposure contributes to cognitive impairment, but relevant mechanism information is limited. Neuroinflammation plays important roles in neurodegenerative disorders. This study aimed to explore whether chronic acrylamide exposure induced neuronal lesions, microglial activation, NLRP3 inflammasome-mediated neuroinflammation and cognitive impairment. For this purpose, 36 Sprague-Dawley (SD) rats were randomly divided into three groups (n = 12/group) and maintained on treated drinking water providing dosages of 0, 0.5, or 5 mg/kg/day ACR for 12 months. Chronic exposure to ACR caused gait abnormality and cognitive dysfunction, which was associated with neuronal lesions, decrease in synapse associated proteins including synapsin I (SYN1), synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), neurogenesis suppression as shown by reduced brain derived neurotrophic factor (BDNF) and doublecortin (DCX) in the hippocampus and frontal cortex. ACR stimulated glial proliferation and microglial activation by increasing GFAP, Iba-1, Iba-1CD68 positive cells. ACR markedly upregulated the protein levels of NLRP3 inflammasome constituents NLRP3, caspase-1 and increased pro-IL-1β and IL-1β. ACR elevated the protein P62 to suppress NLPR3 inflammasome cleavage. Inflammatory cytokines including TNF-α, IL-6 and Cox-2 were also significantly increased after NF-κB pathway activation, which aggravated neuronal lesions and caused memory deficits. This work helped to propose the possible mechanism of chronic exposure of ACR-induced neurotoxicity. 10.1016/j.taap.2020.114949
    MMP-9-BDNF pathway is implicated in cognitive impairment of male individuals with methamphetamine addiction during early withdrawal. Cheng Mei,Liu Qiang,Wang Yan,Hao Yuling,Jing Pengcheng,Jiao Shaoli,Ma Lin,Pan Chenmin,Wu Yulong Behavioural brain research Cognitive impairment is often concomitant with current and abstinent methamphetamine (METH) misuse. However, the mechanism underlying the pathogenesis of cognitive impairment induced by METH remains unclear. As evidence indicates that brain-derived neurotrophic factor (BDNF) is associated with METH addiction, the present study aimed to investigate whether BDNF and the proteins regulating the BDNF signaling pathway might be implicated in the cognitive impairment of the METH abusers during early withdrawal. A total of 171 male subjects were recruited, including 85 METH abstainers and 86 healthy controls. Cognitive function was evaluated with the Montreal Cognitive Assessment (MoCA) screening tool. The levels of serum proteins that regulate the BDNF signaling pathway were measured using enzyme-linked immunosorbent assay kits. 61.18% METH abstainers were determined to have cognitive impairment (MoCA<26). The serum levels of mBDNF, proBDNF, and MMP-9, as well as the ratio of the mBDNF/proBDNF (M/P) were significantly decreased in the cognition-impaired METH abstainers than in the cognition-unimpaired METH abstainers. mBDNF, proBDNF, TrkB, MMP-9, MMP-9 activity, and M/P were significantly correlated with the MoCA score in the METH abstainers. The combination of mBDNF, TrkB, MMP-9, and MMP-9 activity demonstrated excellent diagnostic potential for cognitive impairment of METH abusers during early withdrawal (AUC = 0.978). The results provide the prospective evidence that the MMP-9-BDNF pathway may underlie the pathogenesis of cognitive impairment in METH abusers during early withdrawal. 10.1016/j.bbr.2019.03.020
    Protective effects of tauroursodeoxycholic acid on lipopolysaccharide-induced cognitive impairment and neurotoxicity in mice. Wu Xian,Liu Caihong,Chen Liang,Du Yi-Feng,Hu Mei,Reed Miranda N,Long Yan,Suppiramaniam Vishnu,Hong Hao,Tang Su-Su International immunopharmacology Accumulating evidence has shown that tauroursodeoxycholic acid (TUDCA) is neuroprotective in different animal models of neurological diseases. However, whether TGR5 agonist TUDCA can improve lipopolysaccharide (LPS)-induced cognitive impairment in mice is less clear. Using a model of cognitive impairment with LPS (2.0 μg) we investigated the effects of TUDCA (200 or 400 μg) on cognitive dysfunction and neurotoxicity in mice. Both Morris water maze and Y-maze avoidance tests showed that TUDCA treatment significantly alleviated LPS-induced behavioral impairments. More importantly, we found that TUDCA treatment reversed TGR5 down-regulation, prevented neuroinflammation via inhibiting NF-κB signaling in the hippocampus of LPS-treated mice. Additionally, TUDCA treatment decreased LPS-induced apoptosis through decreasing TUNEL-positive cells and the overexpression of caspase-3, increasing the ratio of Bcl-2/Bax. TUDCA treatment also ameliorated synaptic plasticity impairments by increasing the ratio of mBDNF/proBDNF, the number of dendritic spines and the expression of synapse-associated proteins in the hippocampus. Our results indicated that TUDCA can improve cognitive impairment and neurotoxicity induced by LPS in mice, which is involved in TGR5-mediated NF-κB signaling. 10.1016/j.intimp.2019.03.065
    A Novel Angiotensin-(1-7) Glycosylated Mas Receptor Agonist for Treating Vascular Cognitive Impairment and Inflammation-Related Memory Dysfunction. Hay Meredith,Polt Robin,Heien Michael L,Vanderah Todd W,Largent-Milnes Tally M,Rodgers Kathleen,Falk Torsten,Bartlett Mitchell J,Doyle Kristian P,Konhilas John P The Journal of pharmacology and experimental therapeutics Increasing evidence indicates that decreased brain blood flow, increased reactive oxygen species (ROS) production, and proinflammatory mechanisms accelerate neurodegenerative disease progression such as that seen in vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer's disease and related dementias. There is a critical clinical need for safe and effective therapies for the treatment and prevention of cognitive impairment known to occur in patients with VCID and chronic inflammatory diseases such as heart failure (HF), hypertension, and diabetes. This study used our mouse model of VCID/HF to test our novel glycosylated angiotensin-(1-7) peptide Ang-1-6-O-Ser-Glc-NH2 (PNA5) as a therapy to treat VCID and to investigate circulating inflammatory biomarkers that may be involved. We demonstrate that PNA5 has greater brain penetration compared with the native angiotensin-(1-7) peptide. Moreover, after treatment with 1.0/mg/kg, s.c., for 21 days, PNA5 exhibits up to 10 days of sustained cognitive protective effects in our VCID/HF mice that last beyond the peptide half-life. PNA5 reversed object recognition impairment in VCID/HF mice and rescued spatial memory impairment. PNA5 activation of the Mas receptor results in a dose-dependent inhibition of ROS in human endothelial cells. Last, PNA5 treatment decreased VCID/HF-induced activation of brain microglia/macrophages and inhibited circulating tumor necrosis factor , interleukin (IL)-7, and granulocyte cell-stimulating factor serum levels while increasing that of the anti-inflammatory cytokine IL-10. These results suggest that PNA5 is an excellent candidate and "first-in-class" therapy for treating VCID and other inflammation-related brain diseases. 10.1124/jpet.118.254854
    The triangle of death of neurons: Oxidative damage, mitochondrial dysfunction, and loss of choline-containing biomolecules in brains of mice treated with doxorubicin. Advanced insights into mechanisms of chemotherapy induced cognitive impairment ("chemobrain") involving TNF-α. Ren Xiaojia,Keeney Jeriel T R,Miriyala Sumitra,Noel Teresa,Powell David K,Chaiswing Luksana,Bondada Subbarao,St Clair Daret K,Butterfield D Allan Free radical biology & medicine Cancer treatments are developing fast and the number of cancer survivors could arise to 20 million in United State by 2025. However, a large fraction of cancer survivors demonstrate cognitive dysfunction and associated decreased quality of life both shortly, and often long-term, after chemotherapy treatment. The etiologies of chemotherapy induced cognitive impairment (CICI) are complicated, made more so by the fact that many anti-cancer drugs cannot cross the blood-brain barrier (BBB). Multiple related factors and confounders lead to difficulties in determining the underlying mechanisms. Chemotherapy induced, oxidative stress-mediated tumor necrosis factor-alpha (TNF-α) elevation was considered as one of the main candidate mechanisms underlying CICI. Doxorubicin (Dox) is a prototypical reactive oxygen species (ROS)-generating chemotherapeutic agent used to treat solid tumors and lymphomas as part of multi-drug chemotherapeutic regimens. We previously reported that peripheral Dox-administration leads to plasma protein damage and elevation of TNF-α in plasma and brain of mice. In the present study, we used TNF-α null (TNFKO) mice to investigate the role of TNF-α in Dox-induced, oxidative stress-mediated alterations in brain. We report that Dox-induced oxidative stress in brain is ameliorated and brain mitochondrial function assessed by the Seahorse-determined oxygen consumption rate (OCR) is preserved in brains of TNFKO mice. Further, we show that Dox-decreased the level of hippocampal choline-containing compounds and brain phospholipases activity are partially protected in TNFKO group in MRS study. Our results provide strong evidence that Dox-targeted mitochondrial damage and levels of brain choline-containing metabolites, as well as phospholipases changes decreased in the CNS are associated with oxidative stress mediated by TNF-α. These results are consistent with the notion that oxidative stress and elevated TNF-α in brain underlie the damage to mitochondria and other pathological changes that lead to CICI. The results are discussed with reference to our identifying a potential therapeutic target to protect against cognitive problems after chemotherapy. 10.1016/j.freeradbiomed.2018.12.029
    A mechanistic cohort study evaluating cognitive impairment in women treated for breast cancer. Vardy Janette L,Stouten-Kemperman Myrle M,Pond Gregory,Booth Christopher M,Rourke Sean B,Dhillon Haryana M,Dodd Anna,Crawley Adrian,Tannock Ian F Brain imaging and behavior Some women report cognitive impairment after adjuvant chemotherapy (CTh) for breast cancer. Here we explore cognitive function, and underlying mechanisms with blood tests and functional magnetic resonance imaging (fMRI). Women treated for early breast cancer were recruited to three groups based on self-reported cognitive symptoms (CS) using FACT-Cog scores. CTh + CS+ (n = 44) had received chemotherapy and self-reported cognitive symptoms; CTh + CS- (n = 52) had chemotherapy but did not report cognitive problems; CTh- (n = 30) had not received chemotherapy. Clinical and computer-based neuropsychological tests were performed. Blood tests included 10 cytokines, sex hormones, coagulation factors, and apolipoprotein-E genotype. fMRI (n = 101) was performed while subjects performed an n-back memory task. Participants had median age 50 (range: 29-60) years and were a median of 17 months post-diagnosis. On clinical neuropsychological tests 19% had cognitive impairment using Global Deficit Score, and 36% using International Cancer and Cognition Task Force criteria with no significant differences in cognitive impairment rates between groups. CTh + CS+ had significantly more fatigue, anxiety/depression and poorer quality-of-life than other groups. There was no association between FACT-Cog and neuropsychological scores. There were significant differences in frontal and parietal regions on fMRI scans: CTh- showed hyperactivation compared to chemotherapy-treated groups, CTh + CS+ had more frontal activation than CTh + CS-. Elevated IL-1, IL-2 were associated weakly and IL-8 more strongly with neuropsychological impairment (rho > 0.20). There were no differences in global cognitive impairment between groups. Cognitive symptoms were associated with fatigue and anxiety/depression, but not with objective cognitive impairment. fMRI scans differed among the three groups. 10.1007/s11682-017-9728-5
    [A Structural Model for Chemotherapy Related Cognitive Impairment and Quality of Life in Breast Cancer Patients]. Lee Jung Ran,Oh Pok Ja Journal of Korean Academy of Nursing PURPOSE:This study aimed to develop and test a structural model for chemotherapy-related cognitive impairment of breast cancer patients based on a literature review and Hess and Insel's chemotherapy-related cognitive change model. METHODS:The Participants consisted of 250 patients who were ≥19 years of age. The assessment tools included the Menopause Rating Scale, Symptom Experience Scale, Hospital Anxiety and Depression Scale, Everyday Cognition, and Functional Assessment of Cancer Therapy-Breast Cancer. Data were analyzed using the SPSS 21.0 and AMOS 21.0 programs. RESULTS:The modified model was a good fit for the data. The model fit indices were χ²=423.18 (<.001), χ²/df=3.38, CFI=.91, NFI=.91, TLI=.89, SRMR=.05, RMSEA=.09, and AIC=515.18. Chemotherapy-related cognitive impairment was directly influenced by menopausal symptoms (β=.38, =.002), depression and anxiety (β=.25, =.002), and symptom experiences (β=.19, =.012). These predictors explained 47.7% of the variance in chemotherapy-related cognitive impairment. Depression and anxiety mediated the relations among menopausal symptoms, symptom experiences, and with chemotherapy related cognitive impairment. Depression and anxiety (β=-.51, =.001), symptom experiences (β=-.27, =.001), menopausal symptoms (β=-.22, =.008), and chemotherapy-related cognitive impairment (β=-.15, =.024) had direct effects on the quality of life and these variables explained 91.3%. CONCLUSION:These results suggest that chemotherapy-related toxicity is highly associated with cognitive decline and quality of life in women with breast cancer. Depression and anxiety increased vulnerability to cognitive impairment after chemotherapy. Nursing intervention is needed to relieve chemotherapy-related toxicity and psychological factor as well as cognitive decline for quality of life in patients undergoing chemotherapy. 10.4040/jkan.2019.49.4.375
    Cancer-related cognitive impairment: an update on state of the art, detection, and management strategies in cancer survivors. Lange M,Joly F,Vardy J,Ahles T,Dubois M,Tron L,Winocur G,De Ruiter M B,Castel H Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Advances in diagnostic and therapeutic strategies in oncology have significantly increased the chance of survival of cancer patients, even those with metastatic disease. However, cancer-related cognitive impairment (CRCI) is frequently reported in patients treated for non-central nervous system cancers, particularly during and after chemotherapy. DESIGN:This review provides an update of the state of the art based on PubMed searches between 2012 and March 2019 on 'cognition', 'cancer', 'antineoplastic agents' or 'chemotherapy'. It includes the most recent clinical, imaging and pre-clinical data and reports management strategies of CRCI. RESULTS:Evidence obtained primarily from studies on breast cancer patients highlight memory, processing speed, attention and executive functions as the most cognitive domains impaired post-chemotherapy. Recent investigations established that other cancer treatments, such as hormone therapies and targeted therapies, can also induce cognitive deficits. Knowledge regarding predisposing factors, biological markers or brain functions associated with CRCI has improved. Factors such as age and genetic polymorphisms of apolipoprotein E, catechol-O-methyltransferase and BDNF may predispose individuals to a higher risk of cognitive impairment. Poor performance on neuropsychological tests were associated with volume reduction in grey matter, less connectivity and activation after chemotherapy. In animals, hippocampus-based memory and executive functions, mediated by the frontal lobes, were shown to be particularly susceptible to the effects of chemotherapy. It involves altered neurogenesis, mitochondrial dysfunction or brain cytokine response. An important next step is to identify strategies for managing cognitive difficulties, with primary studies to assess cognitive training and physical exercise regimens. CONCLUSIONS:CRCI is not limited to chemotherapy. A multidisciplinary approach has improved our knowledge of the complex mechanisms involved. Nowadays, studies evaluating cognitive rehabilitation programmes are encouraged to help patients cope with cognitive difficulties and improve quality of life during and after cancer. 10.1093/annonc/mdz410
    Neuronal autoantibodies associated with cognitive impairment in melanoma patients. Bartels F,Strönisch T,Farmer K,Rentzsch K,Kiecker F,Finke C Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Cancer-related cognitive impairment is an important complication in cancer patients, yet the underlying mechanisms remain unknown. Over the last decade, the field of paraneoplastic neurological syndromes has been dramatically changed by the discovery of new neuronal autoantibodies, some of them associated with cognitive impairment. We aimed to assess the prevalence of neuronal autoantibodies in melanoma patients and their association with neurological and cognitive dysfunction. PATIENTS AND METHODS:A total of 157 consecutive melanoma patients with a median age of 63 years were recruited at the Department of Dermatology, Charité-Universitätsmedizin Berlin and tested for neuronal autoantibodies. A comprehensive neuropsychological assessment was carried out in a selected subgroup of 84 patients after exclusion of patients with confounding factors for a cognitive dysfunction, including brain metastases, relevant medication, and neurological disorders. RESULTS:Neuronal autoantibodies were found in 22.3% of melanoma patients. The most frequent antibodies were IgA/IgM anti-NMDAR antibodies. Applying the International Cognition and Cancer Task Force criteria, 36.9% had cognitive impairment, however, with a threefold higher odds in antibody-positive compared with antibody-negative patients (57.1% versus 30.2%, OR = 3.1, 95% CI: 1.1 to 8.6; P = 0.037). In patients with anti-NMDAR antibodies, this impairment increased with higher antibody titers (P = 0.007). Antibody-positive patients had a significantly impaired overall cognitive performance (z-value: -0.38 ± 0.69 versus 0.00 ± 0.56; P = 0.014) as well as significant impairments in tests of memory, attention, and executive function. In a multiple linear regression analysis, autoantibodies were an independent risk factor for cognitive impairment (B = -0.282; 95% CI: -0.492 to -0.071; P = 0.009). Autoantibody seropositivity was associated with immune checkpoint inhibitor treatment and a history of autoimmune diseases. CONCLUSIONS:A large number of melanoma patients harbor neuronal autoantibodies that are associated with significant cognitive impairment affecting memory, attention, and executive function. Neuronal autoantibodies might represent a pathophysiological factor and possible biomarker in the development of cancer-related cognitive impairment. 10.1093/annonc/mdz083
    Associations between inflammatory markers and cognitive function in breast cancer patients receiving chemotherapy. Williams AnnaLynn M,Shah Raven,Shayne Michelle,Huston Alissa J,Krebs Marcia,Murray Nicole,Thompson Bryan D,Doyle Kassandra,Korotkin Jenna,van Wijngaarden Edwin,Hyland Sharon,Moynihan Jan A,Cory-Slechta Deborah A,Janelsins Michelle C Journal of neuroimmunology BACKGROUND:Cancer-related cognitive impairment (CRCI) is often related to chemotherapy. Increased chronic inflammation is believed to play a key role in the development of CRCI related to chemotherapy but studies assessing this hypothesis specifically in patients receiving chemotherapy are rare. METHODS:We assessed several cognitive domains using the Cambridge Neuropsychological Test Automated Battery (CANTAB) in twenty-two breast cancer patients currently receiving chemotherapy. We also measured inflammatory cytokine and receptor (MCP-1, TNF-α, sTNFRI, sTNFRII) concentrations in patient sera using Luminex assays. These concentrations were log-transformed to obtain a normal distribution. Associations between log-transformed cytokines and cognition were evaluated using Pearson correlations and linear regression, taking into account relevant covariates. RESULTS:Increased concentrations of sTNFRI and sTNFRII were associated with poorer performance on the CANTAB Delayed Matching to Sample (DMS, tests visual memory). Increasing sTNFRI levels were negatively correlated with DMS percent correct (r=-0.47, p=0.029) and DMS percent correct after a 12 second (s) delay (r=-0.65, p=0.001). Increasing levels of sTNFRII negatively correlated with DMS percent correct after 12s delay (r=-0.57, p=0.006). After controlling for relevant demographic (i.e. age, education) and clinical variables (i.e. disease stage, regimen type), we found that increased sTNFRI remained significantly related to decline on the DMS at the 12s delay (p=0.018). CONCLUSION:This preliminary study shows a significant association between higher sTNFRI and lower scores on the short-term visual memory delayed match to sample test in breast cancer patients receiving chemotherapy, supporting the hypothesis that sTNFRI is involved in CRCI. 10.1016/j.jneuroim.2017.10.005
    Effect of dexmedetomidine on the cognitive function of patients undergoing gastric cancer surgery by regulating the PI3K/AKT signaling pathway. Wang Zhiyuan,Shen Zijin,Wang Haibin,Zhang Lin,Dong Rong Oncology letters Effect of dexmedetomidine on the cognitive function of patients undergoing gastric cancer surgery by regulating the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway was investigated. A total of 110 patients who were diagnosed and underwent radical gastrectomy in Ruijin Hospital North, Shanghai Jiaotong University School of Medicine from July 2016 to July 2018 were selected. In the experimental group, 60 patients were treated with dexmedetomidine infusion. In the control group, 50 patients were injected with 0.9% sodium chloride injection during the same period. The expression levels of serum inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), PI3K and AKT of patients were compared between the two groups before and after surgery for 1 day. The number of adverse reactions in the two groups was compared. The correlation between mini-mental state examination (MMSE) score and the expression levels of serum IL-6, PI3K and AKT was compared. The levels of serum TNF-α, IL-6, PI3K and AKT after operation for 1 day of patients in the two groups were significantly higher than those before operation (P<0.05), and were lower in the experimental than in the control group (P<0.05). The number of postoperative cognitive dysfunction of patients in the experimental group was lower than that of patients in the control group (P<0.05). The total number of adverse reactions in the control group was higher than that of patients in the experimental group (P<0.05). The MMSE scores of the two groups were decreased at 1 day after operation and were significantly lower in the control group than in the experimental group (P<0.05). The MMSE score was negatively correlated with the expression levels of serum TNF-α, IL-6, PI3K and AKT (P<0.001). Dexmedetomidine can effectively reduce the expression levels of postoperative inflammatory factors in patients undergoing gastric cancer surgery, improve the postoperative cognitive function by regulating PI3K-Akt signaling pathway and promotes the recovery of postoperative cognitive function. 10.3892/ol.2019.11224
    Influence of combined epidural anesthesia on cognitive function, inflammation and stress response in elderly liver cancer patients undergoing surgery. Su Yang,Pu Yanan,Zhao Zhengnan,Yang Xianglong Oncology letters Effects of combined epidural anesthesia on the cognitive function, inflammation and stress response in the elderly liver cancer patients undergoing surgery were explored. Elderly liver cancer patients (n=100) undergoing surgery in the Second Affiliated Hospital of Dalian Medical University from January 2015 to December 2018 were enrolled and randomly divided into observation group (n=50) and control group (n=50). In control group only conventional anesthesia was performed using 2 µg/kg fentanyl, 1.5 mg/kg propofol and 0.2 mg/kg atracurium, in addition to the procedures in the control group, combined epidural anesthesia was administered using 0.5% bupivacaine for 15 sec and maintained via 0.25% bupivacaine in the observation group. The anesthetic effect was observed and the arterial oxygen saturation (SaO), heart rate (HR), mean arterial pressure (MAP) and mini-mental state examination (MMSE) and cognitive function scores by cognitive abilities screening instrument (CASI) were evaluated in the patients, and their blood was drawn to detect the inflammatory factors interleukin (IL)-6, IL-1 and tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), norepinephrine and epinephrine. The observation group exhibited a better anesthetic effect and obviously smaller decreases in the SaO and MAP and increase in HR than the control group (P<0.05). The MMSE and CASI scores, and the content of IL-1, IL-6, TNF-α, MDA, CAT, norepinephrine and epinephrine in the observation group was obviously lower than that in the control group (P<0.05), while the content of SOD was evidently higher than that in the control group (P<0.05). Overall postoperative conditions in the observation group was superior to the control group (P<0.05), with the incidence rate of cognitive disorder lower than that in the control group (P<0.05). Combined epidural anesthesia dramatically improves the postoperative conditions and cognitive function and relieve inflammatory and stress responses in the patients with a better anesthetic effect, thus holding promise for application. 10.3892/ol.2020.11395
    Assessment of cognitive function in patients with metastatic cancer: Are we using the right tools? Kurita Geana Paula,Sandvad Marlene,Lundorff Lena,De Mattos-Pimenta Cibele Andrucioli,Højsted Jette,Sjøgren Per Palliative & supportive care OBJECTIVE:This study aimed at analyzing the validity and reliability of the continuous reaction time (CRT) test, the finger-tapping test (FTT), the Digit Span Test (DST), the Trail Making Test - part B (TMTB), and the Mini-Mental State Examination (MMSE) in patients with metastatic cancer. METHOD:Eighty adult patients and 81 healthy controls were assessed between July of 2010 and November of 2015. The neuropsychological tests were analyzed regarding construct/discriminant/criterion validity and reliability. RESULTS:In terms of construct validity, it was not possible to estimate a model for the MMSE because of a skewed response distribution. For discriminant validity, patients were slower on two measures of the CRT (p = 0.00483, p = 0.00030) and FTT dominant hand (p = 0.00306). Regarding sensitivity and specificity, only the DST and TMTB seemed to predict cognitive deficit; however, the ROC curve areas were ≤ 0.73. In terms of criterion validity, there were few significant correlations between the tests and the sociodemographic and clinical variables, and for the most part were very weak. Reliability was deemed to be adequate for the TMTB, DST, and FTT. SIGNIFICANCE OF RESULTS:The findings of the full validation analyses were not clear-cut. However, CRT test, DST, FTT, and TMTB demonstrated partial positive results, indicating that these tests have good potential for use in clinical settings and require further study. 10.1017/S1478951517000694
    Cognitive function and fatigue after diagnosis of colorectal cancer. Vardy J,Dhillon H M,Pond G R,Rourke S B,Xu W,Dodd A,Renton C,Park A,Bekele T,Ringash J,Zhang H,Burkes R,Clarke S J,Tannock I F Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Cognitive impairment and fatigue have been associated with cancer and its treatment. We present baseline data from a large longitudinal study that evaluates cognitive function, fatigue, and potential underlying mechanisms following diagnosis of colorectal cancer (CRC). PATIENTS AND METHODS:We evaluated CRC patients with stage I-III disease before or after surgery, participants with limited metastatic disease and healthy controls (HC). Neuropsychological evaluation included clinical and computerised tests. Participants completed questionnaires for fatigue and quality of life (QOL)-(FACT-F), anxiety/depression, and cognitive symptoms (FACT-Cog). Ten cytokines, clotting factors, sex hormones, carcinoembryonic antigen (CEA), and apolipoprotein E genotype were evaluated. Primary end points were cognitive function on clinical tests evaluated by a Global Deficit score (GDS) and fatigue. Associations between test results, demographic, and disease related factors were explored. RESULTS:We assessed 291 participants with early-stage disease [median age 59 (23-75) years, 63% men], 72 with metastatic disease, and 72 HC. Using GDS, 45% (126/281) of participants with early-stage CRC had cognitive impairment versus 15% (11/72) of HC (odds ratio 4.51, 95% confidence interval 2.28-8.93; P < 0.001), with complex processing speed, attention/working memory, and verbal learning efficiency being most affected. Women with early-stage CRC had greater cognitive impairment than men [55/105 (52%) versus 71/176 (40%), P < 0.050]. Cognitive symptoms were self-reported by 21% (59/286) of early-stage patients versus 17% (12/72) of HC; fatigue by 52% (149/287) of early-stage patients and 26% (19/72) of HC (P < 0.0001). Women reported more fatigue than men (P = 0.003). Fatigue, QOL, anxiety/depression, and cognitive symptoms were associated with each other (r = 0.43-0.71), but not with neuropsychological performance. Most cytokines were elevated in cancer patients. Cognitive function was not associated with cytokines, sex hormones, clotting factors, CEA, or apolipoprotein E genotype. CONCLUSIONS:The incidence of cognitive impairment was three to five times higher in CRC patients than HC, with women having higher impairment rates than men. The cognitive impairment profile suggests dysfunction primarily in fronto-subcortical brain systems. TRIAL REGISTRATION:NCT00188331. 10.1093/annonc/mdu448
    Role of stress, age and adjuvant therapy in the cognitive function of patients with breast cancer. Papanastasiou Artemis,Seliniotaki Theodora,Rizos Emmanouil,Kampoli Katerina,Ntavatzikos Anastasios,Arkadopoulos Nikolaos,Tsionou Christina,Spandidos Demetrios A,Koumarianou Anna Oncology letters According to data largely obtained from retrospective studies, it has been postulated that chemotherapy exerts an aggravating effect on the cognitive function of patients with breast cancer. Potential individual factors related to the effects of chemotherapy on cognitive function have been indicated, such as age-related cognitive dysfunction and stress. Elderly patients differ from non-elderly patients as regards higher cognitive related comorbidities, such as dementia, as well as regarding lower stress levels, indicating that 'chemobrain' may differentially affect these two age groups. The aim of this review was to discuss the effects of stress and chemotherapy on cognitive dysfunction and identify any potential age-related differences in patients with breast cancer treated with adjuvant chemotherapy. For this purpose, a systematic review of the literature was carried out on the PubMed, Scopus and Web of Science databases. The inclusion criteria were original articles published in peer-reviewed journals, elderly and non-elderly patients with breast cancer, reporting on stress and at least one cognitive parameter pre- and/or post-treatment. Eight studies met the preset criteria and were further analyzed. In total, the data of 1,253 women were included, of whom 800 patients with breast cancer were treated with surgery only, systemic treatment only, or both. Although all the studies included a non-elderly breast cancer patient subpopulation, only two of the studies included patients over 65 years of age. All studies indicated a statistically significant association of stress with various domains of cognitive dysfunction in patients, as shown by either self-completed questionnaires, neuropsychological testing or both. An age over 60 years was linked to fewer cognitive difficulties mediated by lower levels of stress. Thus, the evidence supports the association of stress with cognitive deficits in patients with breast cancer, regardless of the type of cancer-related treatment. Therefore, stress should be appropriately addressed. However, further research is required to investigate the association of stress with cognitive function in elderly patients with breast cancer. 10.3892/ol.2019.10361
    Remifentanil on T lymphocytes, cognitive function and inflammatory cytokines of patients undergoing radical surgery for cervical cancer. Lu X-Y,Chen M,Chen D-H,Li Y,Liu P-T,Liu Y European review for medical and pharmacological sciences OBJECTIVE:To explore the effects of remifentanil on cognitive function, T lymphocyte subsets and inflammatory cytokines of patients undergoing radical surgery for cervical cancer. PATIENTS AND METHODS:A total of 70 patients undergoing radical surgery for cervical cancer in our hospital from August 2014 to January 2017 were selected. They were divided into control group (n=35) and experimental group (n=35). The patients in the control group received intravenous drip of fentanyl, while those in the experimental group received intravenous drip of remifentanil in the surgery. All the patients returned to the wards after surgery. The eye-opening time, extubation time and awaking time of the patients were collected and recorded by specialized surgical nurses. Moreover, the cognitive function of the patients was assessed at the beginning of the surgery and 3 h, 6 h, 12 h, and 24 h after surgery. Blood was drawn at 24 h after surgery, and quantitative analysis of T lymphocyte subsets and inflammatory cytokines of the patients was conducted. RESULTS:The eye-opening time, extubation time, and awaking time in the remifentanil group were significantly earlier than those in the fentanyl group after surgery (p<0.05). At the same time after surgery, the score of mini-mental state examination (MMSE) in the remifentanil group was higher than that in the fentanyl group. The difference was statistically significant (p<0.05). The patients in the experimental group had a relatively low occurrence of cognitive disorder after surgery (p<0.05). The impacts of remifentanil on each type of T lymphocytes and inflammatory cytokines of the patients after surgery were smaller than those of fentanyl. The differences were statistically significant (p<0.05). CONCLUSIONS:Remifentanil can wake patients up early after surgery. Meanwhile, it results in small inflammatory response and stress response, and low occurrence of postoperative cognitive dysfunction in patients. Therefore, it is worthy of being vigorously promoted for clinical application. 10.26355/eurrev_201805_14987
    Cognitive Function in Patients With Colorectal Cancer Who Do and Do Not Receive Chemotherapy: A Prospective, Longitudinal, Controlled Study. Vardy Janette L,Dhillon Haryana M,Pond Gregory R,Rourke Sean B,Bekele Tsegaye,Renton Corrinne,Dodd Anna,Zhang Haibo,Beale Philip,Clarke Stephen,Tannock Ian F Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:Cognitive dysfunction is reported in people with cancer. Therefore, we evaluated longitudinal changes in cognitive function and underlying mechanisms in people with colorectal cancer (CRC) and healthy controls (HCs). PATIENTS AND METHODS:Participants completed cognitive assessments and questionnaires reporting cognitive symptoms, fatigue, quality of life, and anxiety/depression at baseline (before chemotherapy, if given) and 6, 12, and 24 months. Blood tests included cytokines, clotting factors, apolipoprotein E genotype, and sex hormones. Primary end point was overall cognitive function measured by the Global Deficit Score at 12 months. RESULTS:We recruited 289 patients with localized CRC (173 received chemotherapy; median age, 59 years; 63% male), 73 patients with limited metastatic/recurrent CRC, and 72 HCs. Cognitive impairment was more frequent in patients with localized CRC than HCs at baseline (43% v 15%, respectively; P < .001) and 12 months (46% v 13%, respectively; P < .001), with no significant effect of chemotherapy. Attention/working memory, verbal learning/memory, and complex processing speed were most affected. Cognitive impairment was similar in patients with localized and metastatic CRC. Cytokine levels were elevated in patients with CRC compared with HCs. There was no association between overall cognitive function and fatigue, quality of life, anxiety/depression, or any blood test. Cognitive symptoms at 12 months were reported in 25% of patients with localized CRC versus 17% of HCs (P = .19). More participants who received chemotherapy had cognitive symptoms at 6 months (32%) versus those who did not (16%; P = .007), with no significant difference at 12 months (29% v 21%, respectively; P = .19). Objective cognitive function was only weakly associated with cognitive symptoms. CONCLUSION:Patients with CRC had substantially more cognitive impairment at every assessment than HCs, with no significant added effect of chemotherapy. Mechanisms of cognitive impairment remain unknown. 10.1200/JCO.2015.63.0905
    Predicting Patient Reported Outcomes of Cognitive Function Using Connectome-Based Predictive Modeling in Breast Cancer. Henneghan Ashley M,Gibbons Chris,Harrison Rebecca A,Edwards Melissa L,Rao Vikram,Blayney Douglas W,Palesh Oxana,Kesler Shelli R Brain topography Being able to predict who will likely experience cancer related cognitive impairment (CRCI) could enhance patient care and potentially reduce economic and human costs associated with this adverse event. We aimed to determine if post-treatment patient reported CRCI could also be predicted from baseline resting state fMRI in patients with breast cancer. 76 newly diagnosed patients (n = 42 planned for chemotherapy; n = 34 not planned for chemotherapy) and 50 healthy female controls were assessed at 3 times points [T1 (prior to treatment); T2 (1 month post chemotherapy); T3 (1 year after T2)], and at yoked intervals for controls. Data collection included self-reported executive dysfunction, memory function, and psychological distress and resting state fMRI data converted to connectome matrices for each participant. Statistical analyses included linear mixed modeling, independent t tests, and connectome-based predictive modeling (CPM). Executive dysfunction increased over time in the chemotherapy group and was stable in the other two groups (p < 0.001). Memory function decreased over time in both patient groups compared to controls (p < 0.001). CPM models successfully predicted executive dysfunction and memory function scores (r > 0.31, p < 0.002). Support vector regression with a radial basis function (SVR RBF) showed the highest performance for executive dysfunction and memory function (r = 0.68; r = 0.44, p's < 0.001). Baseline neuroimaging may be useful for predicting patient reported cognitive outcomes which could assist in identifying patients in need of surveillance and/or early intervention for treatment-related cognitive effects. 10.1007/s10548-019-00746-4
    Sevoflurane Effect on Cognitive Function and the Expression of Oxidative Stress Response Proteins in Elderly Patients undergoing Radical Surgery for Lung Cancer. Qin Yang,Ni Jinping,Kang Li,Zhong Zhidong,Wang Liren,Yin Shuzhou Journal of the College of Physicians and Surgeons--Pakistan : JCPSP OBJECTIVE:To investigate the effects of sustained inhalation of sevoflurane on cognitive function and the expression of oxidative stress response proteins such as NADPH oxidase subunits NOX2 and NOX4 in elderly patients undergoing radical surgery for lung cancer. STUDY DESIGN:An experimental study. PLACE AND DURATION OF STUDY:Department of Anesthesiology, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, China, from February 2016 to October 2017. METHODOLOGY:Elderly patients who underwent radical surgery for lung cancer were divided into the sevoflurane group and the propofol group, with 52 cases in each group. Sustained inhalation of sevoflurane and propofol was administered to maintain anesthesia in the respective groups. Cognitive function and lung function parameters were compared between the two groups. Serum S100 &beta; levels and expression of NOX2 and NOX4 proteins in peripheral blood mononuclear cells of the two groups were determined. RESULTS:At 24 hours after surgery, the lung function indices of the sevoflurane group such as FEV1, FVC and VC were higher than those of the propofol group (p<0.001, p=0.008 and p=0.002, respectively). At the end of the surgery and at 24 hours after surgery, the MMSE scores of the sevoflurane group were higher than the propofol group (all p<0.001). S100 levels were lower than the propofol group (p=0.003 and p<0.001, respectively). Levels of NADPH oxidase subunits NOX2 and NOX4 proteins in peripheral blood mononuclear cells of the sevoflurane group were lower than the propofol group (p=0.033, p<0.001, p<0.001and p<0.001, respectively). CONCLUSION:Compared with intravenous anesthesia with propofol, general anesthesia with sevoflurane inhalation has little effect on the short-term cognitive function in elderly patients undergoing radical surgery for lung cancer, and can effectively improve lung function. The mechanism may be related to the reduction of the expression of NOX2 and NOX4 proteins. 10.29271/jcpsp.2019.01.12
    Potential Effect of Immunotherapy Agents on Cognitive Function in Cancer Patients. Joly Florence,Castel Hélène,Tron Laure,Lange Marie,Vardy Janette Journal of the National Cancer Institute A paradigm shift is occurring in cancer therapy, where instead of targeting tumor cells, immunotherapy agents (IA) target the immune system to overcome cancer tolerance and to stimulate an antitumor immune response. IA using immune checkpoint inhibitors (CPI) or chimeric antigen receptor T-cells have emerged as the most encouraging approaches to treat cancer patients. CPI are reported to induce moderate-to-severe neurologic immune-related adverse events in less than 1% of patients, whereas chimeric antigen receptor T-cell therapy is associated with frequent neurological toxicities that can be severe or even fatal. Cognitive difficulties have been described following chemotherapy and targeted therapy, but not specifically explored in patients receiving IA. The aim of this review is to establish a picture of the first published studies suggesting some biological and physiopathological effects of IA on cognitive functions among cancer patients. The first results originate from a preclinical study evaluating the role of CPI associated with peripheral radiation on cognitive dysfunction and the recent discovery of the central nervous lymphatic system allowing leukocytes to penetrate the central nervous system. Evaluating possible side effects of IA on cognitive function will be an important challenge for future clinical trials and for better understanding the underlying mechanisms through preclinical animal models. 10.1093/jnci/djz168
    The Role of Inflammation in the Pain, Fatigue, and Sleep Disturbance Symptom Cluster in Advanced Cancer. Kwekkeboom Kristine L,Tostrud Lauren,Costanzo Erin,Coe Christopher L,Serlin Ronald C,Ward Sandra E,Zhang Yingzi Journal of pain and symptom management CONTEXT:Symptom researchers have proposed a model of inflammatory cytokine activity and dysregulation in cancer to explain co-occurring symptoms including pain, fatigue, and sleep disturbance. OBJECTIVES:We tested the hypothesis that psychological stress accentuates inflammation and that stress and inflammation contribute to one's experience of the pain, fatigue, and sleep disturbance symptom cluster (symptom cluster severity, symptom cluster distress) and its impact (symptom cluster interference with daily life, quality of life). METHODS:We used baseline data from a symptom cluster management trial. Adult participants (N = 158) receiving chemotherapy for advanced cancer reported pain, fatigue, and sleep disturbance on enrollment. Before intervention, participants completed measures of demographics, perceived stress, symptom cluster severity, symptom cluster distress, symptom cluster interference with daily life, and quality of life and provided a blood sample for four inflammatory biomarkers (interleukin-1β, interleukin-6, tumor necrosis factor-α, and C-reactive protein). RESULTS:Stress was not directly related to any inflammatory biomarker. Stress and tumor necrosis factor-α were positively related to symptom cluster distress, although not symptom cluster severity. Tumor necrosis factor-α was indirectly related to symptom cluster interference with daily life, through its effect on symptom cluster distress. Stress was positively associated with symptom cluster interference with daily life and inversely with quality of life. Stress also had indirect effects on symptom cluster interference with daily life, through its effect on symptom cluster distress. CONCLUSION:The proposed inflammatory model of symptoms was partially supported. Investigators should test interventions that target stress as a contributing factor in co-occurring pain, fatigue, and sleep disturbance and explore other factors that may influence inflammatory biomarker levels within the context of an advanced cancer diagnosis and treatment. 10.1016/j.jpainsymman.2018.01.008
    Tumor-Associated Fatigue in Cancer Patients Develops Independently of IL1 Signaling. Grossberg Aaron J,Vichaya Elisabeth G,Christian Diana L,Molkentine Jessica M,Vermeer Daniel W,Gross Phillip S,Vermeer Paola D,Lee John H,Dantzer Robert Cancer research Fatigue is the most common symptom of cancer at diagnosis, yet causes and effective treatments remain elusive. As tumors can be highly inflammatory, it is generally accepted that inflammation mediates cancer-related fatigue. However, evidence to support this assertion is mostly correlational. In this study, we directly tested the hypothesis that fatigue results from propagation of tumor-induced inflammation to the brain and activation of the central proinflammatory cytokine, IL1. The heterotopic syngeneic murine head and neck cancer model (mEER) caused systemic inflammation and increased expression of in the brain while inducing fatigue-like behaviors characterized by decreased voluntary wheel running and exploratory activity. Expression of in the brain was not associated with any alterations in motivation, measured by responding in a progressive ratio schedule of food reinforcement, depression-like behaviors, or energy balance. Decreased wheel running occurred prior to detection in the brain, when systemic inflammation was minimal. Furthermore, mice null for two components of IL1β signaling, the type 1 IL1 receptor or the receptor adapter protein MyD88, were not protected from tumor-induced decreases in wheel running, despite attenuated cytokine action and expression. Behavioral and inflammatory analysis of four additional syngeneic tumor models revealed that tumors can induce fatigue regardless of their systemic or central nervous system inflammatory potential. Together, our results show that brain IL1 signaling is not necessary for tumor-related fatigue, dissociating this type of cancer sequela from systemic cytokine expression. These findings challenge the current understanding of fatigue in cancer patients, the most common and debilitating sequela associated with malignancy. . 10.1158/0008-5472.CAN-17-2168
    Sleep disturbance and cancer-related fatigue symptom cluster in breast cancer patients undergoing chemotherapy. Fox Rina S,Ancoli-Israel Sonia,Roesch Scott C,Merz Erin L,Mills Sarah D,Wells Kristen J,Sadler Georgia Robins,Malcarne Vanessa L Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:Sleep disturbance and cancer-related fatigue (CRF) are among the most commonly reported symptoms associated with breast cancer and its treatment. This study identified symptom cluster groups of breast cancer patients based on multidimensional assessment of sleep disturbance and CRF prior to and during chemotherapy. METHODS:Participants were 152 women with stage I-IIIA breast cancer. Data were collected before chemotherapy (T1) and during the final week of the fourth chemotherapy cycle (T2). Latent profile analysis was used to derive groups of patients at each timepoint who scored similarly on percent of the day/night asleep per actigraphy, the Pittsburgh Sleep Quality Index global score, and the five subscales of the Multidimensional Fatigue Symptom Inventory-Short Form. Bivariate logistic regression evaluated if sociodemographic/medical characteristics at T1 were associated with group membership at each timepoint. RESULTS:Three groups (Fatigued with sleep complaints, Average, Minimal symptoms) were identified at T1, and five groups (Severely fatigued with poor sleep, Emotionally fatigued with average sleep, Physically fatigued with average sleep, Average, Minimal symptoms) at T2. The majority of individuals in a group characterized by more severe symptoms at T1 were also in a more severe symptom group at T2. Sociodemographic/medical variables at T1 were significantly associated with group membership at T1 and T2. CONCLUSIONS:This study identified groups of breast cancer patients with differentially severe sleep disturbance and CRF symptom profiles prior to and during chemotherapy. Identifying groups with different symptom management needs and distinguishing groups by baseline sociodemographic/medical variables can identify patients at risk for greater symptom burden. 10.1007/s00520-019-04834-w
    Cognitive and motor aspects of cancer-related fatigue. Feng Li Rebekah,Regan Jeniece,Shrader Joseph A,Liwang Josephine,Ross Alexander,Kumar Saloni,Saligan Leorey N Cancer medicine BACKGROUND:Cancer-related fatigue (CRF) is a debilitating symptom frequently reported by patients during and after treatment for cancer. CRF is a multidimensional experience and is often solely assessed by self-report measures. The goal of the study is to examine the physical and cognitive aspects of self-reported CRF using a cognitive function test and a physical fatigue index in order to provide objective measures that can characterize the CRF phenotype. METHODS:A total of 59 subjects with nonmetastatic prostate cancer receiving external beam radiation therapy were included in the study. Fatigue was measured using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire. Cognitive characteristics of CRF was measured using the Stroop Color-Word Interference computerized test and the motor aspect of fatigue was measured using the static fatigue test using a handgrip dynamometer. FINDINGS:Functional Assessment of Cancer Therapy-Fatigue scores significantly correlated with the Stroop Interference score, but not performance accuracy in all test conditions. Fatigued subjects exhibited a more rapid decline to 50% of maximal strength and increased static fatigue index in the handgrip test, whereas maximal grip strength was not affected. CONCLUSIONS:The results suggest that CRF exhibits both cognitive and physical characteristics. Subjective fatigue was associated with increased time required to overcome cognitive interference, but not cognitive performance accuracy. Fatigued patients exhibited decreased physical endurance and the ability to sustain maximal strength over time. These objective measures may serve as valuable tools for clinicians to detect cognitive and physical impairment associated with CRF. 10.1002/cam4.2490
    Effects of an Exercise Intervention on Cancer-Related Fatigue and Its Relationship to Markers of Oxidative Stress. Repka Chris P,Hayward Reid Integrative cancer therapies BACKGROUND:Although the underlying mechanisms of cancer-related fatigue (CRF) are not fully characterized, treatment-associated oxidative stress may play a role. The purpose of this study was to determine the effect of an exercise intervention on the relationship between CRF and oxidative stress. METHODS:Upon cessation of radiation or chemotherapy, 8 cancer patients participated in a 10-week exercise intervention (EX), while 7 continued standard care (CON). Blood draws and fatigue questionnaires were administered to cancer patients before and after the intervention as well as to 7 age-matched individuals with no cancer history. Changes in plasma 8-hydroxy-deoxyguanosine (8-OHdG), protein carbonyls, antioxidant capacity, and fatigue were compared between groups. Correlations between CRF and oxidative stress were evaluated. RESULTS:Mean total fatigue scores decreased significantly (5.0 ± 2.2 to 2.6 ± 1.5, P < .05) in EX, but not in CON. Antioxidant capacity significantly increased (+41%; P < .05) and protein carbonyls significantly decreased (-36%; P < .05) in EX, but not in CON. Increases in antioxidant capacity were significantly correlated with reductions in affective ( r = -.49), sensory ( r = -.47), and cognitive fatigue ( r = -.58). Changes in total ( r = .46) and affective ( r = .47) fatigue exhibited significant correlations with changes in 8-OHdG over time, while behavioral ( r = .46) and sensory ( r = .47) fatigue changes were significantly correlated with protein carbonyls. CONCLUSIONS:Oxidative stress may be implicated in CRF, while improved antioxidant capacity following an exercise intervention may play a role in mitigating CRF in cancer survivors. 10.1177/1534735418766402
    Inflammation- and angiogenesis-related biomarkers are correlated with cancer-related fatigue in colorectal cancer patients: Results from the ColoCare Study. Himbert Caroline,Ose Jennifer,Lin Tengda,Warby Christy A,Gigic Biljana,Steindorf Karen,Schrotz-King Petra,Abbenhardt-Martin Clare,Zielske Lin,Boehm Juergen,Ulrich Cornelia M European journal of cancer care Cancer-related fatigue is one of the most common side effects of colorectal cancer treatment and is affected by biomedical factors. We investigated the association of inflammation- and angiogenesis-related biomarkers with cancer-related fatigue. Pre-surgery (baseline) serum samples were obtained from n = 236 newly diagnosed colorectal cancer patients. Meso Scale Discovery assays were performed to measure levels of biomarkers for inflammation and angiogenesis (CRP, SAA, IL-6, IL-8, MCP-1, sICAM-1, sVCAM-1, TNFα, VEGFA and VEGFD). Cancer-related fatigue was assessed with the EORTC QLQ-30 questionnaire at baseline and 6 and 12 months post-surgery. We tested associations using Spearman's partial correlations and logistic regression analyses, adjusting for age, sex and body mass index. sICAM-1 and VEGFD showed a significant positive correlation with cancer-related fatigue at baseline and 6-, and 12-month follow-up (sICAM-1: r = 0.19, p = 0.010; r = 0.24, p = 0.004; r = 0.25, p = 0.006; VEGFD: r = 0.20, p = 0.006; r = 0.15, p = 0.06; r = 0.23, p = 0.01 respectively). Biomarkers of inflammation and angiogenesis measured prior to surgery are associated with cancer-related fatigue in colorectal cancer patients throughout various time points. Our results suggest the involvement of overexpressed sICAM-1 and VEGFD in the development of fatigue. 10.1111/ecc.13055
    The role of neuro-immune interactions in cancer-related fatigue: Biobehavioral risk factors and mechanisms. Bower Julienne E Cancer Fatigue is a common and distressing symptom in both patients with cancer and cancer survivors. There is substantial variation in the severity and persistence of cancer-related fatigue that may be driven by individual differences in host factors, including characteristics that predate the cancer experience as well as responses to cancer and its treatment. This review examines biobehavioral risk factors linked to fatigue and the mechanisms through which they influence fatigue across the cancer continuum, with a focus on neuro-immune processes. Among psychosocial risk factors, childhood adversity is a strong and consistent predictor of cancer-related fatigue; other risk factors include history of depression, catastrophizing, lack of physical activity, and sleep disturbance, with compelling preliminary evidence for loneliness and trait anxiety. Among biologic systems, initial work suggests that alterations in immune, neuroendocrine, and neural processes are associated with fatigue. The identification of key risk factors and underlying mechanisms is critical for the development and deployment of targeted interventions to reduce the burden of fatigue in the growing population of cancer survivors. Given the multidimensional nature of fatigue, interventions that influence multiple systems may be most effective. 10.1002/cncr.31790
    Molecular epidemiology, cancer-related symptoms, and cytokines pathway. Reyes-Gibby Cielito C,Wu Xifeng,Spitz Margaret,Kurzrock Razelle,Fisch Michael,Bruera Eduardo,Shete Sanjay The Lancet. Oncology The Human Genome Project and HapMap have led to a better appreciation of the importance of common genetic variation in determining cancer risk, created potential for predicting response to therapy, and made possible the development of targeted prevention and therapeutic interventions. Advances in molecular epidemiology can be used to explore the role of genetic variation in modulating the risk for severe and persistent symptoms, such as pain, depression, and fatigue, in patients with cancer. The same genes that are implicated in cancer risk might also be involved in the modulation of therapeutic outcomes. For example, polymorphisms in several cytokine genes are potential markers for genetic susceptibility both for cancer risk and for cancer-related symptoms. These genetic polymorphisms are stable markers and easily and reliably assayed to explore the extent to which genetic variation might prove useful in identifying patients with cancer at high-risk of symptom development. Likewise, they could identify subgroups who might benefit most from symptom intervention, and contribute to developing personalized and more effective therapies for persistent symptoms. 10.1016/S1470-2045(08)70197-9
    Fatigue and sleep quality are associated with changes in inflammatory markers in breast cancer patients undergoing chemotherapy. Liu Lianqi,Mills Paul J,Rissling Michelle,Fiorentino Lavinia,Natarajan Loki,Dimsdale Joel E,Sadler Georgia Robins,Parker Barbara A,Ancoli-Israel Sonia Brain, behavior, and immunity Fatigue and sleep disturbances are two of the most common and distressing symptoms reported by cancer patients. Fatigue and sleep are also correlated with each other. While fatigue has been reported to be associated with some inflammatory markers, data about the relationship between cancer-related sleep disturbances and inflammatory markers are limited. This study examined the relationship between fatigue and sleep, measured both subjectively and objectively, and inflammatory markers in a sample of breast cancer patients before and during chemotherapy. Fifty-three women with newly diagnosed stage I-III breast cancer scheduled to receive at least four 3-week cycles of chemotherapy participated in this longitudinal study. Fatigue was assessed with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and objective sleep was measured with actigraphy. Three inflammatory markers were examined: Interleukin-6 (IL-6), Interleukin-1 receptor antagonist (IL-1RA) and C-reactive protein (CRP). Data were collected before (baseline) and during cycle 1 and cycle 4 of chemotherapy. Compared to baseline, more fatigue was reported, levels of IL-6 increased and IL-1RA decreased during chemotherapy. Reports of sleep quality remained poor. Mixed model analyses examining changes from baseline to each treatment time point revealed overall positive relationships between changes in total MFSI-SF scores and IL-6, between changes in total PSQI scores and IL-6 and IL-1RA, and between total wake time at night and CRP (all p's<0.05). These relationships suggest that cancer-related fatigue and sleep disturbances may share common underlying biochemical mechanisms. 10.1016/j.bbi.2012.02.001
    Exploring Relationships Among Peripheral Amyloid Beta, Tau, Cytokines, Cognitive Function, and Psychosomatic Symptoms in Breast Cancer Survivors. Henneghan Ashley,Haley Andreana P,Kesler Shelli Biological research for nursing OBJECTIVE:Accelerated brain aging has been proposed to explain cancer-related cognitive impairment, but empirical evidence for this relationship is lacking. The purpose of this study was to evaluate amyloid beta (Aβ) and tau, biomarkers of neurodegeneration, in relation to cognition in breast cancer survivors (BCSs). We explored relationships among peripheral concentrations of Aβ42, Aβ-40, tau, and cytokines; cognitive function; and psychosomatic symptoms in a cohort of BCSs post-chemotherapy. METHODS:This secondary analysis of a cross-sectional study was conducted with 65 BCSs. Serum total Aβ-42, Aβ-40, and tau levels were measured with single molecule array technology. Cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, granulocyte-macrophage colony-stimulating factor [GM-CSF], interferon [IFN]-g, IL-10, IL-12, IL-13, IL1-b, IL-2, IL-4, IL-5, IL-7, and IL-8) were simultaneously measured in serum using multiplex assays. Cognitive function was measured with five standardized neuropsychological tests and psychosomatic symptoms (stress, loneliness, anxiety, depressive symptoms, fatigue, sleep quality, and daytime sleepiness) with self-report questionnaires. Data analyses included correlations and random forest regression (RFR). RESULTS:Significant correlations were identified among hip-to-waste ratio, number of treatment modalities, Aβ-42, Aβ-40, and tau levels (s = .27-.35, s < .05). RFR modeling including Aβ-42, Aβ-40, tau, and cytokines as features explained significant variance in cognitive function ( = .71, = 9.01, < .0001) and psychosomatic symptoms ( = .74, = 10.22, < .0001). CONCLUSIONS:This study suggests that neurodegenerative biomarkers interact with cytokines to influence cognitive functioning and psychosomatic symptoms in BCSs following chemotherapy, but additional research is needed. 10.1177/1099800419887230
    C-reactive protein predicts fatigue independently of depression in breast cancer patients prior to chemotherapy. Pertl Maria M,Hevey David,Boyle Noreen T,Hughes Martina M,Collier Sonya,O'Dwyer Anne-Marie,Harkin Andrew,Kennedy M John,Connor Thomas J Brain, behavior, and immunity Heightened inflammatory activity has been proposed as a mechanism for the development of cancer-related fatigue (CRF), a common and distressing condition that can negatively affect quality of life. Inflammation is also implicated in the pathogenesis of depression, and depression is a strong predictor of CRF. Thus, the role of the pro-inflammatory cytokine network in CRF may be mediated by depression or both conditions may share similar underlying physiological processes. The current study investigated associations between fatigue, depression and inflammatory cytokine (IFN-γ, IL-6, TNF-α) and CRP concentrations, as well as kynurenine pathway (KP) activation, in 61 breast cancer patients prior to chemotherapy. Changes in inflammatory markers and KP activation over time were also explored, and associations with changes in fatigue and depression were examined. Higher levels of CRP were significantly correlated with fatigue and depression before chemotherapy; nevertheless, CRP predicted fatigue independently of depression. Although greater kynurenine concentrations were associated with increased immune activation, there was no evidence that the KP played a role in fatigue or depression. Furthermore, no relationships emerged between either fatigue or depression and IFN-γ, IL-6, or TNF-α before chemotherapy. Nevertheless, kynurenine levels pre- and post-treatment significantly predicted changes in depression, suggesting that heightened KP activation may contribute to depressive symptoms in patients treated for cancer. In addition, IL-6 significantly covaried with fatigue. These preliminary findings provide some support for the idea that low-grade inflammation contributes to the development of CRF, independently of depression; however, there was no evidence that this is mediated by KP activity. 10.1016/j.bbi.2013.07.177
    The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure. Lacourt Tamara E,Vichaya Elisabeth G,Chiu Gabriel S,Dantzer Robert,Heijnen Cobi J Frontiers in behavioral neuroscience Chronic or persistent fatigue is a common, debilitating symptom of several diseases. Persistent fatigue has been associated with low-grade inflammation in several models of fatigue, including cancer-related fatigue and chronic fatigue syndrome. However, it is unclear how low-grade inflammation leads to the experience of fatigue. We here propose a model of an imbalance in energy availability and energy expenditure as a consequence of low-grade inflammation. In this narrative review, we discuss how chronic low-grade inflammation can lead to reduced cellular-energy availability. Low-grade inflammation induces a metabolic switch from energy-efficient oxidative phosphorylation to fast-acting, but less efficient, aerobic glycolytic energy production; increases reactive oxygen species; and reduces insulin sensitivity. These effects result in reduced glucose availability and, thereby, reduced cellular energy. In addition, emerging evidence suggests that chronic low-grade inflammation is associated with increased willingness to exert effort under specific circumstances. Circadian-rhythm changes and sleep disturbances might mediate the effects of inflammation on cellular-energy availability and non-adaptive energy expenditure. In the second part of the review, we present evidence for these metabolic pathways in models of persistent fatigue, focusing on chronic fatigue syndrome and cancer-related fatigue. Most evidence for reduced cellular-energy availability in relation to fatigue comes from studies on chronic fatigue syndrome. While the mechanistic evidence from the cancer-related fatigue literature is still limited, the sparse results point to reduced cellular-energy availability as well. There is also mounting evidence that behavioral-energy expenditure exceeds the reduced cellular-energy availability in patients with persistent fatigue. This suggests that an inability to adjust energy expenditure to available resources might be one mechanism underlying persistent fatigue. 10.3389/fnbeh.2018.00078
    Interleukin 6-independent metabolic reprogramming as a driver of cancer-related fatigue. Grossberg Aaron J,Vichaya Elisabeth G,Gross Phillip S,Ford Bianca G,Scott Kiersten A,Estrada Darlene,Vermeer Daniel W,Vermeer Paola,Dantzer Robert Brain, behavior, and immunity Fatigue is a common and debilitating symptom of cancer with few effective interventions. Cancer-related fatigue (CRF) is often associated with increases in inflammatory cytokines, however inflammation may not be requisite for this symptom, suggesting other biological mediators also play a role. Because tumors are highly metabolically active and can amplify their energetic toll via effects on distant organs, we sought to determine whether CRF could be explained by metabolic competition exacted by the tumor. We used a highly metabolically active murine E6/E7/hRas model of head and neck cancer for this purpose. Mice with or without tumors were submitted to metabolic constraints in the form of voluntary wheel running or acute overnight fasting and their adaptive behavioral (home cage activity and fasting-induced wheel running) and metabolic responses (blood glucose, ketones, and liver metabolic gene expression) were monitored. We found that the addition of running wheel was necessary to measure activity loss, used as a surrogate for fatigue in this study. Tumor-bearing mice engaged in wheel running showed a decrease in blood glucose levels and an increase in lactate accumulation in the skeletal muscle, consistent with inhibition of the Cori cycle. These changes were associated with gene expression changes in the livers consistent with increased glycolysis and suppressed gluconeogenesis. Fasting also decreased blood glucose in tumor-bearing mice, without impairing glucose or insulin tolerance. Fasting-induced increases in wheel running and ketogenesis were suppressed by tumors, which was again associated with a shift from gluconeogenic to glycolytic metabolism in the liver. Blockade of IL-6 signaling with a neutralizing antibody failed to recover any of the behavioral or metabolic outcomes. Taken together, these data indicate that metabolic competition between the tumor and the rest of the organism is an important component of fatigue and support the hypothesis of a central role for IL-6-independent hepatic metabolic reprogramming in the pathophysiology of CRF. 10.1016/j.bbi.2020.05.043
    Perceived cognitive impairment in people with colorectal cancer who do and do not receive chemotherapy. Dhillon Haryana M,Tannock Ian F,Pond Gregory R,Renton Corrinne,Rourke Sean B,Vardy Janette L Journal of cancer survivorship : research and practice PURPOSE:Cognitive symptoms are common after cancer, but poorly associated with neuropsychological results. We previously reported colorectal cancer (CRC) patients had more cognitive impairment than controls. Here, we explore relationships between cognitive symptoms and neuropsychological domains. METHODS:Subjects with CRC (N = 362) and 72 healthy controls completed neuropsychological assessments and Functional Assessment of Cancer Therapy-Cognition (FACT-COG) at baseline (pre-chemotherapy) and 6, 12, and 24 months. Associations between neuropsychological and FACT-COG scores were explored: perceived cognitive impairment (PCI), perceived cognitive ability (PCA), impact of PCI on quality of life (CogQOL). RESULTS:Of 362 CRC subjects, 289 had loco-regional disease and 173 received chemotherapy (CTh+). At baseline, groups did not differ on total FACT-COG, PCI, or PCA scores. All scores, except PCA, were worse at 6 months in CTh+. CRC patients not receiving chemotherapy did not differ from controls on FACT-COG domains. PCA associated weakly (r = 0.28-0.34) with attention/executive function, visual memory, and global deficit score. There was no association between PCI and neuropsychological domains. Fatigue, anxiety/depression, and poorer quality of life were associated with PCI and CogQOL (r = 0.44-0.51) in CRC patients. CONCLUSIONS:No association was seen between total FACT-COG or PCI, and neuropsychological domains. A weak-moderate association was found between PCA and attention/executive function and visual memory. TRIAL REGISTRATION:The study was registered with clinicaltrials.gov (trial registration: NCT00188331). IMPLICATIONS FOR CANCER SURVIVORS:Cognitive symptoms are associated with fatigue, anxiety/depression, and poorer quality of life, and do not appear to be related to actual cognitive performance. Rates were lower than that reported in breast cancer survivors. Cognitive symptoms were greatest in those who received chemotherapy, with no significant difference between the non-chemotherapy survivors and healthy controls. 10.1007/s11764-017-0656-6
    Cognitive Dysfunction and Its Predictors in Adult Patients With Cancer Receiving Chemotherapy: A Cross-Sectional Correlational Study. Wazqar Dhuha Youssef The journal of nursing research : JNR BACKGROUND:Chemotherapy-related cognitive dysfunction, one of the most frequently reported symptoms in patients with cancer, has a negative impact on the daily lives of patients. No research has examined cognitive dysfunction and its potential predictors in adult patients with cancer receiving chemotherapy in Saudi Arabia. PURPOSE:The purpose of this study was to examine the sociodemographic, clinical, and psychological factors associated with cognitive dysfunction in adult patients with cancer receiving chemotherapy. METHODS:A cross-sectional correlational study was carried out with a convenience sample of 100 adult patients with cancer receiving chemotherapy at a university teaching hospital in Saudi Arabia. The Montreal Cognitive Assessment, the Hospital Anxiety and Depression Scale, and sociodemographic and clinical surveys were completed by participants. Descriptive statistics and linear regression were used to analyze the data. RESULTS:The data showed that the participants experienced moderate-to-severe cognitive dysfunction. Participants performed poorly in the divided attention and memory cognitive domains. Age, educational level, and depression factors were found to be significant predictors of cognitive dysfunction. CONCLUSIONS/IMPLICATIONS FOR PRACTICE:Cognitive dysfunction is commonly seen in patients with cancer receiving chemotherapy. Chemotherapy, age, and psychological factors increase susceptibility to cognitive dysfunction in adult patients with cancer. Oncology nurses should be aware that patients with cancer may be extremely vulnerable to cognitive dysfunction. Furthermore, age and psychological factors must be considered when developing symptom management and supportive care intervention programs to reduce the incidence of negative cognitive outcomes in this population. 10.1097/jnr.0000000000000340
    Chemotherapy-related cognitive impairment: mechanisms, clinical features and research perspectives. Cascella Marco,Di Napoli Raffaela,Carbone Domenico,Cuomo Gaia Francesca,Bimonte Sabrina,Muzio Maria Rosaria Recenti progressi in medicina The term chemotherapy-related cognitive impairment (CRCI), or cognitive dysfunction, or chemo fog, or chemo brain, is referred to a decline in a variety of neuropsychological tasks after chemotherapy, or following other anticancer treatments such as radiation therapy or surgery, in patients with non-central nervous system cancers. Furthermore, several pieces of evidence suggest that clinical manifestations of cognitive impairment may occur in cancer patients, prior to chemotherapy or in those not treated with cancer therapies. In these circumstances, it should be more appropriate to use the term cancer-related cognitive dysfunction. Because there is no consensus about its definition and diagnostic criteria, no specific test for CRCI diagnose exists. Whatever the cause, this manifestation of central nervous system toxicity is of increasing concern as the survival rates for cancer have improved steadily and, in turn, cognitive dysfunction can negatively impact the patients and cancer survivors' quality of life. The aim of this work is to offer an overview of the topic and recommendations for future research. 10.1701/3031.30289
    Age- and gender-dependent changes in circulating concentrations of tumor necrosis factor-α, soluble tumor necrosis factor receptor-1 and sulfated glycosaminoglycan in healthy people. Komosinska-Vassev Katarzyna,Olczyk Pawel,Winsz-Szczotka Katarzyna,Klimek Katarzyna,Olczyk Krystyna Clinical chemistry and laboratory medicine BACKGROUND:In this study, the effect of gender and physiological ageing on circulating concentrations of plasma sulfated glycosaminoglycans (sGAG) as well as molecules involved in pro- (tumor necrosis factor-α; TNF-α) and anti-inflammatory responses (soluble tumor necrosis factor receptor-1, sTNF-RI) were assessed. The relationships between sGAG and molecules involved in age-dependent extracellular matrix (ECM) remodeling during physiological ageing were also investigated. METHODS:Circulating TNF-α and sTNF-RI were measured in 91 healthy volunteers using enzyme-linked immunosorbent assays. sGAG were quantified using an Alcian blue-binding assay. RESULTS:A linear age-related decline in plasma sGAG was found during the first five decades of life (r=-0.61, p<0.05), followed by an increase occurring only in females (r=0.46, p<0.05). Circulating TNF-α concentrations were inversely correlated with age (r=-0.24, p<0.05) over the lifetime. For TNF-α, the observed changes were gender specific. Serum sTNF-RI concentrations were not affected by age in either men or women. A significant positive correlation was found between the concentrations of TNF-α and both sGAG (r=0.22, p<0.05) and sTNF-RI (r=0.21, p<0.05). CONCLUSIONS:Our data demonstrate that physiological ageing is associated with ECM remodeling, reflected by plasma sGAGs concentrations. Changes in the ECM metabolism during the ageing process were influenced by circulating TNF-α. Furthermore, serum concentrations of biomolecules involved in pro- and anti-inflammatory responses are not increased in healthy elderly subjects. 10.1515/CCLM.2011.007
    Symptom clusters in patients with breast cancer receiving radiation therapy. Chow Selina,Wan Bo Angela,Pidduck William,Zhang Liying,DeAngelis Carlo,Chan Stephanie,Yee Caitlin,Drost Leah,Leung Eric,Sousa Philomena,Lewis Donna,Lam Henry,Chow Ronald,Lock Michael,Chow Edward European journal of oncology nursing : the official journal of European Oncology Nursing Society PURPOSE:Symptoms experienced by breast cancer patients often cluster together in groups known as "symptom clusters". The aim was to determine the symptom clusters in women with non-metastatic breast cancer treated by radiation therapy (RT). METHODS:Edmonton Symptom Assessment Scale (ESAS) scores were taken from breast cancer patients receiving RT before, at completion of RT, and after RT. Exploratory factor analysis (EFA), principal component analysis (PCA), and hierarchical cluster analysis (HCA) were used to identify symptom clusters among the nine ESAS items at all three time points. RESULTS:This study included 1224 patients. The PCA and EFA identified the same two symptom clusters before the start of RT: 1) pain, tiredness, nausea, drowsiness, appetite, and dyspnea; 2) depression, anxiety, and wellbeing. The HCA further split the symptoms into three clusters. Wellbeing, depression, and anxiety consistently clustered together. Among the ESAS scores collected at the end of and after RT, each statistical method identified different symptom clusters. For the symptom clusters experienced at the end of RT, the following symptoms were always in the same cluster: wellbeing, depression, and anxiety; nausea and appetite; drowsiness and dyspnea. Following RT, depression and anxiety consistently clustered together, with nausea and appetite in a second cluster. CONCLUSION:Among the symptom clusters derived before, at the end of RT, and after RT, the following symptoms consistently presented together: depression and anxiety, nausea and appetite, pain and tiredness, and drowsiness, dyspnea, and tiredness. Understanding symptom clusters in this population can improve management of symptoms. 10.1016/j.ejon.2019.07.004