Mitochondrial DNA is a sensitive surrogate and oxidative stress target in oral cancer cells.

Cellular oxidative stress mediated by intrinsic and/or extrinsic reactive oxygen species (ROS) is associated with disease pathogenesis. Oxidative DNA damage can naturally be substituted by mitochondrial DNA (mtDNA), leading to base lesion/strand break formation, copy number changes, and mutations. In this study, we devised a single test for the sensitive quantification of acute mtDNA damage, repair, and copy number changes using supercoiling-sensitive quantitative PCR (ss-qPCR) and examined how oxidative stress-related mtDNA damage responses occur in oral cancer cells. We observed that exogenous hydrogen peroxide (H2O2) induced dynamic mtDNA damage responses, as reflected by early structural DNA damage, followed by DNA repair if damage did not exceed a particular threshold. However, high oxidative stress levels induced persistent mtDNA damage and caused a 5-30-fold depletion in mtDNA copy numbers over late responses. This dramatic depletion was associated with significant growth arrest and apoptosis, suggesting persistent functional consequences. Moreover, oral cancer cells responded differentially to oxidative injury when compared with normal cells, and different ROS species triggered different biological consequences under stress conditions. In conclusion, we developed a new method for the sensitive detection of mtDNA damage and copy number changes, with exogenous H2O2 inducing dynamic mtDNA damage responses associated with functional changes in stressed cancer cells. Finally, our method can help characterize oxidative DNA damage in cancer and other human diseases.

An evidence-based breathing exercise intervention for chronic pain management in breast cancer survivors: A phase II randomized controlled trial.

OBJECTIVE: Explore the preliminary effects of a breathing exercise (BE) intervention on chronic pain among breast cancer survivors. METHODS: This two-parallel-arm, open-label pilot randomized controlled trial recruited 72 breast cancer survivors who were randomly allocated to either the control or intervention group (n = 36 each). Both groups received usual care and a pain information booklet, while the intervention group received 4 weeks of additional BE. The primary clinical outcome was measured using the Brief Pain Inventory (BPI), with secondary clinical outcomes measured by the Hospital Anxiety and Depression Scale (HADS), Quality of Life Patient/Cancer Survivor Version in Chinese (QOLCSV-C), and Functional Assessment of Cancer Therapy- Breast (FACT-B) immediately post-intervention and at 4-week follow-up. Both adjusted and unadjusted Generalized Estimating Equation models were utilized to assess the BE's potential effects, with safety assessed through participant self-report. RESULTS: Sixty-eight participants completed the study. Statistical significance was observed in BPI in both adjusted and unadjusted models at post-intervention and follow-up (p < 0.05). BE demonstrated positive effects on anxiety, depression and quality of life improvement across all measures and timepoints in both adjusted and unadjusted models (p < 0.05). The effect sizes were smaller in the adjusted model. Three mild transient discomforts were reported associated with BE practice including dizziness, tiredness and yawning, without requirement of medical treatment. No severe adverse events occurred. CONCLUSION: This BE intervention appears effective in alleviating chronic pain, anxiety and depression, and improving quality of life for breast cancer survivors. Fully powered large-scale studies are required to confirm its effects.

Residential mobility and liver cancer risk: findings from a prospective cohort study in Chinese women.

BACKGROUND: Residential mobility is believed to influence the occurrence and development of cancer; however, the results are inconclusive. Furthermore, limited studies have been conducted on Asian populations. This study aimed to evaluate the relationship between residential mobility and liver cancer risk among Chinese women. METHODS: We enrolled 72,818 women from urban Shanghai between 1996 and 2000, and then followed them until the end of 2016. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association between residential mobility and liver cancer risk. A linear trend test was conducted by ranking variables. A sensitivity analysis was also conducted, excluding participants with follow-up times of less than 2 years, to prevent potential bias. RESULTS: During the 1,269,765 person-years of follow-up, liver cancer was newly diagnosed in 259 patients. Domestic migration (HR = 1.47, 95% CI, 1.44-1.50), especially immigration to Shanghai (HR = 1.47, 95% CI, 1.44-1.50) was associated with an increased risk of liver cancer. In addition, migration frequency, age at initial migration and first immigration to Shanghai had linear trends with an increased liver cancer risk (Ptrend <0.001). The results were similar when excluding participants with less than two years of follow-up. CONCLUSIONS: The possible association between residential mobility and a higher risk of liver cancer in women could suggest the need for effective interventions to reduce adverse environmental exposures and enhance people's health.

Effects of nonpharmacological interventions on symptom clusters in breast cancer survivors: A systematic review of randomized controlled trials.

Objective: To summarize nonpharmacological interventions and assess their effects on symptom clusters and quality of life (QoL) in breast cancer (BC) survivors. Methods: Seven English and three Chinese electronic databases and three clinical trial registries were searched from January 2001 to August 2023. A narrative approach was applied to summarize the data. The primary outcome was symptom clusters measured by any patient-reported questionnaires, and the secondary outcomes were QoL and intervention-related adverse events. Results: Six published articles, one thesis, and one ongoing trial involving 625 BC survivors were included. The fatigue-sleep disturbance-depression symptom cluster was the most frequently reported symptom cluster among BC survivors. The nonpharmacological interventions were potentially positive on symptom clusters and QoL among the BC survivors. However, some of the included studies exhibited methodological concerns (e.g., inadequate blinding and allocation concealment). The intervention protocols in only two studies were developed following a solid evidence-based approach. Adverse events related to the targeted interventions were reported in six included studies, with none performing a causality analysis. Conclusions: The nonpharmacological interventions could be promising strategies for alleviating symptom clusters in BC survivors. Future studies should adopt rigorously designed, randomized controlled trials to generate robust evidence. Systematic review registration: INPLASY202380028.

Quality appraisal and descriptive analysis of clinical practice guidelines for self-managed non-pharmacological interventions of cardiovascular diseases: a systematic review.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death around the world. Most CVDs-related death can be prevented by the optimal management of risk factors such as unhealthy diet and physical inactivity. Clinical practice guidelines (CPGs) for CVDs, provide some evidence-based recommendations which help healthcare professionals to achieve the best care for patients with CVDs. This systematic review aims to appraise the methodological quality of CPGs systematically and summarize the recommendations of self-managed non-pharmacological interventions for the prevention and management of CVDs provided by the selected guidelines. METHODS: A comprehensive electronic literature search was conducted via six databases (PubMed, Medline, The Cochrane Library, Embase, CINAHL, and Web of Science), seven professional heart association websites, and nine guideline repositories. The Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument was adopted to critically appraise the methodological quality of the selected guidelines. Content analysis was used to summarise recommended self-managed non-pharmacological interventions for CVDs. RESULTS: Twenty-three CPGs regarding different CVDs were included, in which four guidelines of CVDs, three for coronary heart diseases, seven for heart failure, two for atrial fibrillation, three for stroke, three for peripheral arterial disease, and one for hypertrophic cardiomyopathy. Twenty CPGs were appraised as high quality, and three CPGs as moderate quality. All twenty-three CPGs were recommended for use with or without modification. The domain of "Editorial Independence" had the highest standardized percentage (93.47%), whereas the domain of "Applicability" had the lowest mean domain score of 75.41%. The content analysis findings summarised some common self-managed non-pharmacological interventions, which include healthy diet, physical activity, smoking cessation, alcohol control, and weight management. Healthy diet and physical acidity are the most common and agreed on self-managed interventions for patients with CVDs. There are some inconsistencies identified in the details of recommended interventions, the intervention itself, the grade of recommendation, and the supported level of evidence. CONCLUSION: The majority of the summarized non-pharmacological interventions were strongly recommended with moderate to high-quality levels of evidence. Healthcare professionals and researchers can adopt the results of this review to design self-managed non-pharmacological interventions for patients with CVDs.

Exploring approaches to contemporary clinical incident analysis methods within acute care settings: a scoping review protocol.

OBJECTIVE: This review will explore the literature on contemporary incident analysis methods used in acute hospital settings, identifying types and characteristics of these methods and how they are used to minimize, prevent, or learn from errors and improve patient safety. INTRODUCTION: Safety is a major focus in health care; however, despite best efforts, errors and incidents still occur, leading to harm or potential harm to patients, families, carers, staff, or the organization. Incident analysis methods aim to reduce risk of harm. Traditional methods have been criticized for failing to consider the complexity of health care and the dynamic nature of acute care settings. Alternative methodologies are being sought to achieve higher levels of patient safety and care quality care in hospitals. Learning from errors and communicating with those involved in incidents are key requirements in contemporary incident analysis. INCLUSION CRITERIA: This review will consider empirical research published since 2013, reporting on the use of clinical incident analysis methods within acute care settings. The review will explore ways in which consumers or stakeholders (eg, clinicians or other hospital workers, patients, families, carers, visitors) have been included in these analysis methods and how data have been used to support changes in the service or organization. METHODS: Following JBI methods and PRISMA-ScR reporting guidance, we will search PubMed, CINAHL (EBSCOhost), Embase, Scopus, the Cochrane Library, Web of Science, and ProQuest Dissertations and Theses. Studies will be reviewed independently, with results presented in tables, figures, and narrative summaries according to the concepts of interest.

Somatic acupressure for the fatigue-sleep disturbance-depression symptom cluster in breast cancer survivors: A phase II randomized controlled trial.

OBJECTIVE: To evaluate the feasibility of the somatic acupressure (SA) for managing the fatigue-sleep disturbance-depression symptom cluster (FSDSC) among breast cancer (BC) survivors and its preliminary effects. METHODS: In this Phase II randomized controlled trial (RCT), 51 participants were randomised evenly into the true SA group, sham SA group, and usual care group. All the participants received usual care. The two SA groups performed additional true or sham self-acupressure daily for seven weeks. The primary outcomes related to the assessment of participants' recruitment and compliance with study questionnaires and interventions. Clinical outcomes assessed the preliminary effects of SA on fatigue, sleep disturbance, depression, and quality of life. Semi-structured interviews were undertaken to capture participants' experiences of participating in this study. The statistical effects of the intervention on the outcomes were modelled in repeated measures ANOVA and adjusted generalized estimating equations. RESULTS: Forty-five participants completed the SA intervention. No adverse events were reported. Over 85% of the participants could sustain for 25 days or more and 15 min or more per session, but the adherence to the intervention requirement was yet to improve. The group by time effect of the FSDSC and depression were significant (p < 0.05). Qualitative findings showed that participants positively viewed SA as a beneficial strategy for symptom management. CONCLUSIONS: The SA intervention protocol and the trial procedures were feasible. The results demonstrated signs of improvements in targeted outcomes, and a full-scale RCT is warranted to validate the effects of SA on the FSDSC.

Tn antigen promotes breast cancer metastasis via impairment of CASC4.

Breast cancer is one of the most serious and deadly cancers in women worldwide, with distant metastases being the leading cause of death. Tn antigen, a tumor-associated carbohydrate antigen, was frequently detected in breast cancer, but its exact role in breast cancer metastasis has not been well elucidated. Here we investigated the impact of Tn antigen expression on breast cancer metastasis and its underlying mechanisms. The expression of Tn antigen was induced in two breast cancer cell lines by deleting T-synthase or Cosmc, both of which are required for normal O-glycosylation. It showed that Tn-expressing cancer cells promoted epithelial-mesenchymal transition (EMT) and metastatic features as compared to Tn(-) control cells both in vitro and in vivo. Mechanistically, we found that cancer susceptibility candidate 4 (CASC4), a heavily O-glycosylated protein, was significantly downregulated in both Tn(+) cells. Overexpression of CASC4 suppressed Tn-induced activation of EMT and cancer metastasis via inhibition of Cdc42 signaling. Furthermore, we confirmed that O-glycosylation is essential for the functional role of CASC4 because defective O-glycosylated CASC4 (mutant CASC4, which lacks nine O-glycosylation sites) exerted marginal metastatic-suppressing effects in comparison with WT CASC4. Collectively, these data suggest that Tn-mediated aberrant O-glycosylation contributes to breast cancer metastasis via impairment of CASC4 expression and function.

Experiences of Chinese advanced cancer patients after attending a "four-stage" death education programme: A qualitative study.

PURPOSE: This study aimed to explore the experiences of cancer patients who participated in and completed a "four-stage" death education programme based on knowledge-attitude-practice theory. METHODS: This study employed a qualitative descriptive design. Semistructured interviews with an interview guide were used to collect data. Fifteen cancer patients who participated in and completed the "four-stage" death education programme (from November 10, 2021, to December 29, 2021) were recruited via purposive sampling. The "four-stage" death education programme model was developed based on knowledge-attitude-practice theory and included eight death education modules. Each interview was audio-recorded and transcribed verbatim. Generic analysis was used to conduct data analysis by coding, classifying, and extracting themes. RESULTS: Five themes were identified: the gradual shift of death cognition towards objective reality, a decrease in death anxiety, patients' early thoughts concerning issues related to death and preparation ahead of death, patients' improved ability to respond to death incidents, and patients' increased focus on cherishing the remainder of their lives and living in the moment. CONCLUSIONS: Cancer patients accept and respond effectively to the implementation of a "four-stage" death education programme based on knowledge-attitude-practice theory. These findings can help cancer patients improve their reasonable perception of death and reduce their doubts and confusion concerning death.

Quality of life patient/cancer survivor version in Chinese cancer survivors: A validation study.

Objective: To validate the Chinese version of the Quality of Life (QoL) Patient/Cancer Survivor Version (QOLCSV-C) for measuring QoL in Chinese cancer survivors. Methods: The study followed a seven-step research practice guideline for cross-cultural research instrument validation study including translation, adaptation, and psychometric assessment. A forward- and backward-translation procedure was approached, followed by cultural adaptation and acceptability assessment. For its psychometric properties, its concurrent validity with the Functional Assessment of Cancer Therapy-General (FACT-G) was examined with correlation analysis. The internal consistency (Cronbach's alpha) and item-total and item-subtotal correlations of the QOLCSV-C were obtained. Factor analyses were conducted. Floor and ceiling effects and the discriminant performance of the selected variables on QOLCSV-C score were also examined. Results: The QOLCSV-C was translated from the 41-item QOLCSV with four domains: psychological, physical, spiritual and social well-being. The content validity was excellent (CVI â€‹= â€‹1.00). Time spent to complete the QOLCSV-C was about 10 â€‹min. The QOLCSV-C was found easy to use, appropriate in length, and reflective of their QoL. The strong correlation between QOLCSV-C and FACT-G indicates a satisfactory concurrent validity (Spearman's rho â€‹= â€‹0.765, P â€‹< â€‹0.001, n â€‹= â€‹205). The overall internal consistency of the QOLCSV-C (Cronbach's alpha â€‹= â€‹0.888) and the split-half reliability (Spearman-Brown r â€‹= â€‹0.918) were excellent. Most of the items show moderate to strong item-total correlation. The exploratory factor analysis revealed a four-factor solution, and confirmatory factor analysis has a satisfactory model fit with indicative items. None of the total scores of QOLCSV-C reveal the floor or ceiling effect. For discriminant performance, variables demonstrating significant between-group differences include sleep quality, pain, fatigue, nausea, physical health, and financial burden. Conclusions: The QOLCSV-C is a reliable and valid instrument for measuring the QoL in Chinese cancer survivors. Future studies can explore the factor structure, gender universal or specific items, and significant predictors of QoL of cancer survivors in different cultures.

ERK inhibition aids IFN-ß promoter activation during EV71 infection by blocking CRYAB degradation in SH-SY5Y cells.

Enterovirus 71 (EV71) can cause severe hand-foot-and-mouth disease with neurological complications. It has evolved multiple mechanisms to compromise the host type I interferon (IFN-I) response. In neuronal cells, EV71-mediated IFN-I antagonism may be associated with neural precursor cell-expressed developmentally downregulated 4-like (Nedd4L), the E3 ubiquitin ligase that can interact with alphaB-crystallin (CRYAB) in the regulation of Nav1.5 stability. Here, we investigated the effect of CRYAB stability on IFN-ß promoter activity in neuronal SH-SY5Y cells infected with EV71, and its relations to Nedd4 L and extracellular signal-regulated kinases (ERK). Results showed that EV71 infection significantly caused CRYAB degradation via the Nedd4L-proteasome pathway, which required ERK-mediated phosphorylation of Serine 45 in CRYAB. Subsequently, it was observed that siRNA- or EV71-mediated CRYAB reduction limited Poly(dAT)-activated IFN-ß promoter, and CRYAB stabilisation by U0126-mediated inhibition of ERK activation remarkably enhanced the activity of IFN-ß promoter upon EV71 challenge. Collectively, we elucidate a novel mechanism by which ERK activation contributes to EV71 immune escape via CRYAB/IFN-ß axis in SH-SY5Y cells, indicating that perturbing ERK activation is desirable for anti-EV71 therapy.

Effects of somatic acupoint stimulation on anxiety and depression in cancer patients: An updated systematic review of randomized controlled trials.

OBJECTIVES: To explore the effectiveness of somatic acupoint stimulation (SAS) for cancer patients with anxiety and depression. METHODS: Thirteen electronic databases were searched systematically until August 2022. Randomized controlled trials (RCTs) investigating SAS for anxiety and/or depression in cancer patients were retrieved. Methodological quality of the included studies was assessed by utilizing the Cochrane Back Review Group Risk of Bias Assessment Criteria. Evidence level was assessed by using the approach of Grading of Recommendations, Assessment, Development and Evaluations (GRADE). Both meta-analysis and descriptive analysis were conducted for outcome assessment. RESULTS: Twenty-eight records were finally included including 22 journal articles and six ongoing registered clinical trials. The overall methodological quality and level of evidence of the included studies were suboptimal, with no high-quality evidence identified. Moderate evidence showed that SAS could significantly decrease the anxiety of cancer patients (Acupuncture: [random effect model, SMD = -0.52, 95% CI = -0.79 to -0.24, p = 0.0002] and Acupressure: [random effect model, SMD = -0.89, 95% CI = -1.25 to -0.52, p < 0.00001]. While for depression, although the data analysis indicated that SAS can decrease depression significantly (Acupuncture: [random effect model, SMD = -1.26, 95% CI = -2.08 to -0.44, p = 0.003] and Acupressure: [random effect model, SMD = -1.42, 95% CI = -2.41 to -0.42, p = 0.005]), relevant evidence was rated as low. No statistically significant difference was identified between true and sham acupoints stimulation for both anxiety and depression. CONCLUSIONS: This systematic review provides the latest research evidence to support SAS as a promising intervention for alleviating anxiety and depression in cancer patients. However, the research evidence should be interpreted prudently as methodological concerns were identified in some included studies, and some sub-group analyses were performed with a relatively small sample size. More rigorously designed large-scale RCTs with placebo-controlled comparisons are warranted to generate high-quality evidence. REGISTRATION: The systematic review protocol has been registered with PROSPERO (CRD42019133070).

Development and Validation of an Evidence-Based Breathing Exercise Intervention Protocol for Chronic Pain Management in Breast Cancer Survivors.

BACKGROUND: Breathing exercise has been utilized as a promising approach to pain management in cancer survivors. However, the development process of the breathing exercise intervention protocol was rarely reported. AIM: To develop an evidence-based breathing exercise intervention protocol for chronic pain management in breast cancer survivors and to provide a detailed account of the intervention development process. METHODS: The study design was guided by the Medical Research Council Framework for Developing and Evaluating Complex Intervention. The breathing exercise intervention development process adopted phase one of the Medical Research Council Framework for Developing and Evaluating Complex Intervention framework. The content validity index was applied to determine the consensus of the appropriateness of the breathing exercise intervention protocol among the panel experts. RESULTS: The preliminary breathing exercise intervention protocol was developed based on fight-or-flight theory and vagus nerve theory, and the best available research evidence identified from seven systematic reviews, three clinical trials, and four practice recommendations. The breathing exercise intervention was designed as slow deep pursed-lip breathing with a time ratio of inspiration to expiration 1:2-3. The intensity of the breathing exercise was determined as 3 to 5 sessions a day, 5 minutes per session, for 4 weeks. The content validity of the breathing exercise intervention protocol was excellent as consensus was achieved among all panel experts with both the item-level and scale-level CVIs reaching 1.0. CONCLUSIONS: This study developed an evidence-based breathing exercise intervention protocol for chronic pain management in breast cancer survivors. The protocol is well-supported by the relevant theories, research evidence, practice recommendations, and experts' consensus.

Breathing Exercises for Pain Management in Cancer Survivors: A Systematic Review.

OBJECTIVES: Unmanaged pain significantly affects cancer survivors' quality of life. Nurses should play a significant role in pain management through non-pharmacological interventions. This review aims to explore the efficacy and safety of breathing exercises for pain management in all cancer survivors. DESIGN: A systematic review. DATA SOURCES: Thirteen databases, including PubMed, EMBase, CENTRAL, MEDLINE, CINAHL, JBI, Science Direct, Scopus, SocINDEX, Web of Science, PsycINFO, CNKI, and Wan Fang, were searched from inception to May, 2021. REVIEW/ANALYSIS METHODS: Studies that focused on the efficacy of breathing exercises for pain management, regardless of the age of the cancer survivors, were included. Cochrane tools were used for the quality appraisal of the included studies. Because of the limited number of studies, descriptive data analysis was used to summarize the results. RESULTS: Ten studies were included. Slow pursed lip breathing showed benefits for post-surgical pain. Contradictory findings were identified in the Enhanced Recovery After Surgery for post-surgical pain. Slow deep breathing and Hey-Hu regular breathing techniques were effective for pain management in pediatric cancer patients. The Active Cycle of Breathing Technique and five-minute mindful breathing did not have any statistically significant effects on pain relief. Quality of life was measured in three studies, with some improvement. Only one study addressed adverse events and reported that no adverse events occurred. CONCLUSIONS: Breathing exercises may be a promising approach to pain relief in cancer survivors. However, more rigorously designed studies are required to establish the evidence.

Feasibility and potential effects of breathing exercise for chronic pain management in breast cancer survivors: study protocol of a phase II randomised controlled trial.

INTRODUCTION: Chronic pain is a common symptom significantly affecting the quality of life of breast cancer survivors. Despite the achievement of pharmacological interventions, the barriers associated with this approach such as inaccessibility, misuse and side effects drive research into effective non-pharmacological interventions to improve chronic pain management, quality of life, anxiety and depression. Breathing exercise (BE) can be a promising option, but research evidence is sparse. This pilot study aims to examine the feasibility and preliminary effect of using an evidence-based BE intervention for chronic pain management in breast cancer survivors. METHOD AND ANALYSIS: This study will be a two-parallel-arm, open-labelled, phase II randomised controlled trial with 1:1 allocation. Seventy-two participants will be recruited from a tertiary hospital in China and randomly allocated to either a BE intervention group (n=36) or a control group (n=36). The participants in the intervention group will receive the usual care, a pain information booklet and a 4-week self-administered BE intervention; the participants in the control group will receive the usual care and the pain information booklet only. The assessment will be conducted at three time points: baseline (week 0), immediately after the intervention completion (week 5) and 4 weeks after the intervention completion (week 9). The primary outcomes will be the acceptability and feasibility assessment of the study protocol and methodological procedures. The secondary outcomes will be the effects of BE on pain, quality of life, anxiety and depression in breast cancer survivors. Descriptive statistics will be applied to present the primary outcomes and the Generalised Estimating Equation Model will be utilised to analyse the clinical outcomes. ETHICS AND DISSEMINATION: This study has received ethical approvals from the Human Research Ethics Committee at Charles Darwin University (H21089) and the Clinical Trial Ethics Committee at the Affiliated Hospital of Southwest Medical University (KY2022107). Findings from this study will be presented at academic conferences and submitted to peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05257876.

Effects of exercise interventions on cancer-related fatigue in breast cancer patients: an overview of systematic reviews.

OBJECTIVE: This overview of systematic reviews aims to critically appraise and consolidate evidence from current systematic reviews (SRs)/meta-analyses on the effects of exercise interventions on cancer-related fatigue (CRF) in breast cancer patients. METHODS: SRs/meta-analyses that explored the effects of exercise interventions on CRF in breast cancer patients compared with the routine methods of treatment and care were retrieved from nine databases. The methodological quality of the included SRs was appraised using A MeaSurement Tool to Assess systematic Reviews II (AMSTAR II). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to calculate the grading of outcomes in the included SRs. The exercise type, frequency, duration, and inclusion/absence of supervision were further evaluated with subgroup analyses. The Stata 16.0 software was utilized for data analysis. RESULTS: Twenty-nine reviews were included. The overall methodological quality and level of evidence of the included reviews were unsatisfactory, with only three reviews rated as high methodological quality and no review identified as high-quality evidence. Moderate certainty evidence indicated that exercise could improve fatigue in breast cancer patients (SMD = - 0.40 [95%CI - 0.58, - 0.22]; P = 0.0001). Subgroup analysis based on the types of exercise showed that yoga (SMD = - 0.30 [95%CI - 0.56, - 0.05]; I2 = 28.7%) and aerobic exercise (SMD = - 0.29 [95%CI - 0.56, - 0.02]; I2 = 16%) had a significantly better effect on CRF in breast cancer patients; exercising for over 6 months (SMD = - 0.88 [95%CI - 1.59, - 0.17]; I2 = 42.7%; P = 0.0001), three times per week (SMD = - 0.77 [95%CI - 1.04, - 0.05]; I2 = 0%; P = 0.0001), and for 30 to 60 min per session (SMD = - 0.81 [95%CI - 1.15, - 0.47]; I2 = 42.3%; P = 0.0001) can contribute to a moderate improvement of CRF. Supervised exercise (SMD = - 0.48 [95%CI - 0.77, - 0.18]; I2 = 87%; P = 0.001) was shown to relieve CRF. CONCLUSION: Exercise played a favorable role in alleviating CRF in breast cancer. Yoga was recommended as a promising exercise modality for CRF management in the majority of the included studies. Exercising for at least three times per week with 30 to 60 min per session could be recommended as a suitable dosage for achieving improvement in CRF. Supervised exercise was found to be more effective in alleviating CRF than unsupervised exercise. More rigorously designed clinical studies are needed to specify the exact exercise type, duration, frequency, and intensity to have an optimal effect on CRF in breast cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: CRD42020219866.

The effect of an evidence-based Tai chi intervention on the fatigue-sleep disturbance-depression symptom cluster in breast cancer patients: A preliminary randomised controlled trial.

PURPOSE: To explore the potential effects of Tai chi on the fatigue-sleep disturbance-depression symptom cluster (FSDSC) among breast cancer (BC) patients. METHODS: This study was conducted as a preliminary randomized controlled trial among 72 BC patients (36 Tai chi and 36 control participants). All the participants were provided with routine care, while participants in the Tai chi group received an additional 8-week Tai chi intervention. Participants' fatigue, sleep disturbance and depression were assessed by the Brief Fatigue Inventory, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale-Depression. Participants' quality of life (QoL) was assessed by the Functional Assessment of Cancer Therapy-Breast. Both covariates-unadjusted and adjusted GEE models were run to assess the effects of Tai chi intervention on the FSDSC and QoL and the relevant impacts of the covariates. RESULTS: Sixty-nine participants completed this study. In the unadjusted GEE model, compared with the control group and baseline, participants in the Tai chi group showed significant reductions in fatigue (p < 0.001), sleep disturbance (p < 0.001) and depression (p = 0.006), as well as a significant improvement in QoL (p = 0.032) at immediately post-intervention and four-week follow-up. The positive regression coefficients of the adjusted GEE model showed fatigue, sleep disturbance and depression can have impacts on each other (all at p < 0.05). CONCLUSION: Tai chi as an adjuvant intervention to routine care could relieve the symptom cluster of fatigue, sleep disturbance and depression and improve QoL among BC patients.

An Evidence-Based Somatic Acupressure Intervention Protocol for Managing the Breast Cancer Fatigue-Sleep Disturbance-Depression Symptom Cluster: Development and Validation following the Medical Research Council Framework.

BACKGROUND: Somatic acupoint stimulation (SAS) has been frequently utilised as a promising intervention for individual cancer-related symptom management, such as fatigue, sleep disturbance and depression. However, research evidence regarding the role of SAS in mitigating the fatigue-sleep disturbance-depression symptom cluster (FSDSC) has been scant. This study was conducted to develop an evidence-based SAS intervention protocol that can be further implemented in a Phase II randomized controlled trial (RCT) to manage the FSDSC in breast cancer survivors. METHODS: The Medical Research Council Framework for Developing and Evaluating Complex Intervention (MRC framework) was employed to guide the development procedures of the SAS intervention protocol, including the identification of an existing evidence base, the identification of theories and practice standards, and the validation of the SAS intervention protocol. A content validity study was performed through an expert panel to assess the scientific and practical appropriateness of the SAS intervention protocol. The content validity index (CVI), including item-level CVI and protocol-level CVI, were calculated to evaluate the consensus level of the expert panel. RESULTS: Key components of the SAS protocol, including the acupoint formula, the SAS modality, technique, intensity and frequency were identified for both a true and placebo SAS intervention based on the best available research evidence retrieved from systematic reviews, clinical trials, and relevant theories, particularly regarding the inflammatory process, yin-yang theory, zang-fu organs and meridians theory, and acupressure practical standards. The true SAS intervention was determined as daily self-administered acupressure on specific acupoints for seven weeks. The placebo SAS was designed as light acupressure on non-acupoints with the same frequency and duration as the true SAS. Excellent content validity was achieved after one round of expert panel assessment, with all the key components of the true and placebo SAS protocols rated as content valid (CVI ranged from 0.86 to 1.00). CONCLUSIONS: A research-informed, theory-driven and practically feasible SAS intervention protocol for the FSDSC management in breast cancer survivors was developed following the MRC framework. The feasibility and acceptability of the SAS intervention will be further tested in breast cancer survivors through a Phase II RCT.

Prevalence and correlates of joint pain among Chinese breast cancer survivors receiving aromatase inhibitor treatment.

BACKGROUND: Aromatase inhibitor (AI)-induced joint pain is a common toxicity of AI treatment. Although many studies have been conducted to examine the occurrence and severity of AI-induced joint pain in breast cancer survivors, none of the studies focused on the Chinese population with breast cancer. Given that the differences in cultural background and the genetic structure between Asians and Caucasians may contribute to different phenotypes of joint pain, this cross-sectional study was therefore conducted to examine the prevalence of AI-induced joint pain among Chinese breast cancer survivors receiving AI treatment and the correlates of pain. METHODS: This cross-sectional study was conducted in a tertiary hospital in China. Breast cancer survivors undergoing AI treatment were recruited to complete the following questionnaires: a self-designed baseline data form, the Nordic Musculoskeletal Questionnaire (NMQ), the Brief Pain Inventory (BPI), the 36-Item Short Form Health Survey (SF-36), and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Based on the assessment results of NMQ (if the participant indicated pain in specific body parts), participants were then invited to complete other questionnaires to specifically assess the joint symptoms, including the Oxford Knee Score (OKS), the Oxford Hip Score (OHS), the Michigan Hand Outcomes Questionnaire (MHQ), and the Manchester Foot Pain Disability Questionnaire (MFPDQ). Descriptive analysis was used to analyse participants' baseline data and the prevalence of pain. Stepwise multiple regression was used to identify the correlates of pain. RESULTS: Four hundred and ten participants were analysed. According to the NMQ, 71.7% of the participants experienced joint symptoms in at least one joint, and the most frequently mentioned joint was knee (39.0%). The diagram in BPI indicated that 28.0% of the participants had the worst pain around knees. In patients with knee pain, the mean OKS score was 40.46 ± 6.19. The sub-scores of BPI for pain intensity and pain interference were 1.30 ± 1.63 and 1.24 ± 1.79, respectively. Patients' poorer physical well-being/functioning, previous use of AI treatment, presence of osteoarthritis, and receiving of physiotherapy were identified as four common correlates of greater severity of pain and pain interference (p < 0.05). CONCLUSIONS: Chinese breast cancer survivors can experience joint pain at various locations, particularly knees. In addition to increasing the use of interventions for pain alleviation, a comprehensive assessment of survivors' conditions such as physical functioning, history of AI treatment, and presence of osteoarthritis should be emphasized to identify survivors who need more attention and tailored interventions.

Self-Managed Non-Pharmacological Interventions for Breast Cancer Survivors: Systematic Quality Appraisal and Content Analysis of Clinical Practice Guidelines.

Background: A growing number of clinical practice guidelines (CPGs) regarding non-pharmacological interventions for breast cancer survivors are available. However, given the limitations in guideline development methodologies and inconsistent recommendations, it remains uncertain how best to design and implement non-pharmacological strategies to tailor interventions for breast cancer survivors with varied health conditions, healthcare needs, and preferences. Aim: To critically appraise and summarise available non-pharmacological interventions for symptom management and health promotion that can be self-managed by breast cancer survivors based on the recommendations of the CPGs. Methods: CPGs, which were published between January 2016 and September 2021 and described non-pharmacological interventions for breast cancer survivors, were systematically searched in six electronic databases, nine relevant guideline databases, and five cancer care society websites. The quality of the included CPGs was assessed by four evaluators using The Appraisal of Guidelines for Research and Evaluation, second edition tool. Content analysis was conducted to synthesise the characteristics of the non-pharmacological interventions recommended by the included CPGs, such as the intervention's form, duration and frequency, level of evidence, grade of recommendation, and source of evidence. Results: A total of 14 CPGs were included. Among which, only five were appraised as high quality. The "range and purpose" domain had the highest standardized percentage (84.61%), while the domain of "applicability" had the lowest (51.04%). Five CPGs were rated "recommended", seven were "recommended with modifications", and the other two were rated "not recommended". The content analysis findings summarised some commonly recommended self-managed non-pharmacological interventions in the 14 guidelines, including physical activity/exercise, meditation, hypnosis, yoga, music therapy, stress management, relaxation, massage and acupressure. Physical activity/exercise was the most frequently recommended approach to managing psychological and physical symptoms by the included guidelines. However, significant variations in the level of evidence and grade of recommendation were identified among the included CPGs. Conclusion: Recommendations for the self-managed non-pharmacological interventions were varied and limited among the 14 CPGs, and some were based on medium- and low-quality evidence. More rigorous methods are required to develop high-quality CPGs to guide clinicians in offering high-quality and tailored breast cancer survivorship care.