Differential effects of desvenlafaxine on hot flashes in women with breast cancer taking tamoxifen: a randomized controlled trial.

Hot flashes (HF) are a common adverse event of prolonged tamoxifen use in women with estrogen receptor-positive breast cancer, impacting psychiatric health and quality of life. While desvenlafaxine does not interact with tamoxifen, its efficacy and safety in breast cancer patients remain unstudied. This phase 3, four-week, multi-center, three-arm, parallel-group, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of desvenlafaxine for treating HF in women with breast cancer taking tamoxifen, assessing potential differential effects in patients with psychiatric and inflammatory conditions. Between December 2017 and February 2019, 57 women aged 19 or older, regularly taking tamoxifen as adjuvant therapy, experiencing moderate-to-severe HFs for more than a month, were randomized to receive desvenlafaxine 50 mg/day (D-50), desvenlafaxine 100 mg/day (D-100), or placebo for four weeks. The primary endpoint was the change rate in HF scores over four weeks, with adverse events as a secondary endpoint. Both desvenlafaxine arms demonstrated greater HF score reductions compared to placebo: D-50 (2.20 points/week, 95% CI: 0.71, 3.68) and D-100 (2.34 points/week, 95% CI: 0.92, 3.76). Notably, D-50 arm showed significantly greater efficacy in patients with depression or elevated inflammation. Desvenlafaxine offers an effective and safe treatment regimen for HF in women with breast cancer taking tamoxifen. The presence of depression and inflammation may guide optimal desvenlafaxine dosing. (Trial Registration: ClinicalTrials.gov Identifier: NCT02819921).

Differences in severity of chemotherapy-induced nausea and vomiting between neoadjuvant and adjuvant chemotherapy in patients with breast cancer: analysis of data from two prospective observational studies.

PURPOSE: We assessed the differences in chemotherapy-induced nausea and vomiting (CINV) severity in patients with breast cancer, receiving neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC). METHODS: CINV severity in patients on anthracycline-based NAC (n = 203) and AC (n = 79) was assessed at baseline (C0) and after the first and fourth chemotherapy using a 10-point Likert scale. Group-by-time interaction term was used to evaluate the effect of the group on changes in CIN (cCIN) and CIV (cCIV) from C0 to the follow-up periods (C1, C4). If insignificant, group effects were analyzed without the interaction term. Subgroup analysis was performed based on age 50. In statistical analyses, sociodemographic and clinical variables that differed between groups were adjusted for. RESULTS: The effect of group by follow-up period was not significant in cCIN and cCIV. The AC group showed a significantly higher change in the severity of cCIN compared to the NAC group (estimated mean = 1.133, 95% CI = 0.104-2.161, p = 0.031), but there was no difference in cCIV. In those ≤ 50 years, significant differences in cCIN severity (estimated mean = 1.294, 95% CI = 0.103-2.484, p = 0.033) were observed, but not in cCIV. In those > 50 years, neither cCIN nor cCIV differed significantly between groups. CONCLUSIONS: NAC in breast cancer patients showed less severe CIN than adjuvant chemotherapy AC, but not in those over 50. Clinicians should recognize that the severity of CIN may vary across different chemotherapy settings and adjust their management accordingly. TRIAL REGISTRATION: The clinical trial registration ( www. CLINICALTRIALS: gov ) numbers were NCT01887925 (the registration date is from June 20, 2013, to November 27, 2015) and NCT02011815 (the registration date is from December 10, 2013, to September 22, 2019).

The Effect of Temperament on the Association Between Pre-treatment Anxiety and Chemotherapy-Related Symptoms in Patients With Breast Cancer.

OBJECTIVE: Pre-treatment anxiety (PA) before chemotherapy increases complaints of chemotherapy-related symptoms (CRS). The results on the association have been inconsistent, and the effect of temperament remains unclear. We aimed to determine whether PA is a risk factor for CRS and the effect of differing temperaments on CRS. METHODS: This prospective study comprised 176 breast cancer patients awaiting adjuvant chemotherapy post-surgery. We assessed CRS, PA, and temperament using the MD Anderson Symptom Inventory (MDASI), the Hospital Anxiety and Depression Scale, and the short form of the Temperament and Character Inventory-Revised, respectively. The MDASI was re-administered three weeks after the first chemo-cycle. RESULTS: PA showed weak positive correlation with several CRS after the first cycle; no CRS was significantly associated with PA when pre-treatment depressive symptoms and baseline CRS were adjusted in multiple regression analysis. Moderation model analysis indicated that the PA effect on several CRS, including pain, insomnia, anorexia, dry mouth, and vomiting, was moderated by harm avoidance (HA) but not by other temperament dimensions. In particular, PA was positively associated with CRS in patients with low HA. CONCLUSION: The results in patients with low HA indicate that more attention to PA in patients with confident and optimistic temperaments is necessary.

The longitudinal effects of chronotype on chemotherapy-induced nausea and vomiting in patients with breast cancer receiving neoadjuvant chemotherapy.

OBJECTIVE: The object of this longitudinal cohort study was to investigate whether chronotype affects the incidence of chemotherapy-induced nausea and vomiting (CINV) among patients with breast cancer. METHODS: The study included a total of 203 breast cancer patients who received neoadjuvant chemotherapy using a regimen of doxorubicin and cyclophosphamide with high emetogenicity. Patients received four cycles of chemotherapy in approximately three months. Patients completed questionnaires including the Munich Chronotype Questionnaire (MCTQ) before the first chemotherapy and the Multinational Association of Supportive Care in Cancer Antiemesis Tool (MAT) after each of the four chemotherapy sessions. To confirm the effect of chronotype on CINV during the four cycles, we performed statistical analyses using a generalized estimating equation (GEE). RESULTS: CINV occurred in 108 (53.2%), 112 (55.2%), 102 (50.3%), and 62 (30.5%) patients during four cycles of treatment. In the GEE approach, late and early chronotypes (vs. intermediate chronotype) were associated with an increased risk of CINV (late chronotype: odds ratio [OR], 2.06; 95% confidence interval [CI], 1.41-2.99; p < 0.001, early chronotype: OR, 1.84; CI, 1.25-2.73; p = 0.002), which remained significant even after adjusting for age, BMI, antiemetic treatment, history of nausea and vomiting, anxiety, and sleep quality. CONCLUSION: Chronotype affected CINV across the four cycles of neoadjuvant chemotherapy in patients with breast cancer, suggesting the need to consider chronotype in predicting and managing CINV.

Morning Chronotype Decreases the Risk of Chemotherapy-Induced Peripheral Neuropathy in Women With Breast Cancer.

BACKGROUND: The purpose of this longitudinal prospective cohort study was to investigate the role of chronotype in the incidence of chemotherapy-induced peripheral neuropathy (CIPN) among women with breast cancer. METHODS: We recruited women with breast cancer awaiting adjuvant chemotherapy, including four cycles of docetaxel. Participants reported peripheral neuropathy symptoms of numbness/tingling at the baseline, and at 4weeks after completion of chemotherapy. Candidate psychiatric factors associated with CIPN were assessed at the baseline, using the Composite Scale of Morningness, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale. To examine the association between chronotype and CIPN, we built logistic regression models, adjusting for demographic, clinical, and other psychiatric variables. RESULTS: Among 48 participants, 29 participants developed CIPN. The morning chronotype was inversely associated with CIPN (odds ratio, 0.06; confidence interval, 0.01-0.74; P = 0.028) after adjusting for age, BMI, education, type of operation, alcohol use, smoking, sleep quality, depression, and anxiety. CONCLUSION: Our results suggest that the morning chronotype is a protective factor against the development of CIPN in patients with breast cancer who were treated with docetaxel. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01887925.

Psychiatric symptoms mediate the effect of resilience on health-related quality of life in patients with breast cancer: Longitudinal examination.

OBJECTIVE: Patients with breast cancer receiving neoadjuvant chemotherapy are at increased risk of poor health-related quality of life (HRQOL). This study examined clinical caseness on depression and anxiety mediate the relationship between resilience and HRQOL in patients with breast cancer. METHODS: A total of 193 patients with breast cancer undergoing neoadjuvant chemotherapy completed questionnaires including the Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Cancer Therapy-Breast before the first session (T0), before the start of the last session (T1), and 6 months after the end (T2) of chemotherapy. Mediation analyses using a bootstrapping method was performed. RESULTS: The indirect effect (IE) through T1 depression was significant (IE through depression = 0.043, 95% confidence interval [CI] [0.002-0.090]), while IE through T1 anxiety was not significant (IE through anxiety = 0.037, 95% CI [-0.010-0.097]) in the association between T0 resilience and T2 HRQOL. CONCLUSIONS: Clinical caseness on HADS depression subscale during chemotherapy was a mediating factor of the relationship between resilience before chemotherapy and HRQOL after chemotherapy in patients with breast cancer receiving neoadjuvant chemotherapy. Depression during chemotherapy in patients with breast cancer may be a target symptom of screening and intervention to maintain the HRQOL after chemotherapy. Also, patients with low resilience are more likely to develop depression during chemotherapy, and clinicians should carefully monitor whether depression occurs in these patients with low resilience.

Phenomenological examinations of delirium in advanced cancer patients: exploratory structural equation modelling and latent profile analysis.

BACKGROUND: This study examined phenomenological manifestations of delirium in advanced cancer patients by examining the factor structure of the Delirium Rating Scale-Revised-98 (DRS-R-98) and profiles of delirium symptoms. METHODS: Ninety-three patients with advanced cancer admitted to inpatient palliative care units in South Korea were examined by psychiatrists using the DRS-R-98 and the Confusion Assessment Method (CAM). The factor structure of the DRS-R-98 was examined by exploratory structural equation modelling analysis (ESEM) and profiles of delirium were examined by latent profile analysis (LPA). RESULTS: CAM-defined delirium was present in 66.6% (n = 62) of patients. Results from the ESEM analysis confirmed applicability of the core and noncore symptom factors of the DRS-R-98 to advanced cancer patients. LPA identified three distinct profiles of delirium characterizing the overall severity of delirium and its core and noncore symptoms. Class 1 (n = 55, 59.1%) showed low levels of all delirium symptoms. Class 2 (n = 17, 18.3%) showed high levels of core symptoms only, whereas Class 3 (n = 21, 22.6%) showed high levels of both core and noncore symptoms except motor retardation. CONCLUSIONS: Clinical care for delirium in advanced cancer patients may benefit from consideration of the core and noncore symptom factor structure and the three distinct phenomenological profiles of delirium observed in the present study.

Prevalence and comorbidities of adult adhd in male military conscripts in korea: Results of an epidemiological survey of mental health in korean military service.

We assessed the prevalence/comorbidities of attention deficit hyperactivity disorder (ADHD) in Korean servicemen using the Epidemiological Survey of Mental Health in Military Service in Korea. A total of 3,441 participants were assessed for adult ADHD, depression, social anxiety, generalized anxiety, somatization, insomnia, suicidality, cigarette dependence, and alcohol dependence using a self-report scale. Participants were also asked to rank their perception of their career prospects, health status, and quality of life on a Likert scale. Participants were classified as ADHD according to the WHO A-ADHD self-report scale. Firth multiple logistic regression and Cochran-Armitage trend tests were used to identify the risks of comorbidities and trends of self-perception between the two groups. ADHD (prevalence: 2.8%) was significantly associated with social anxiety (OR, 40.52; 95% CI 25.14-65.74), generalized anxiety (OR, 28.21; 95% CI 17.37-45.69), depression (OR, 16.36; 95% CI 10.50-25.52), somatization (OR, 14.47; 95% CI 9.21-22.76), suicidality (OR, 11.03; 95% CI 6.67-17.86), and insomnia (OR, 5.92; 95% CI 3.68-9.35). Servicemen with ADHD had negative perceptions (p <0.001) of their career prospects, health status, and quality of life compared to servicemen without ADHD. It is essential to revise the enlistment criteria for individuals with ADHD or to develop management programs for servicemen with ADHD.

The effect of perceived social support on chemotherapy-related symptoms in patients with breast cancer: A prospective observational study.

OBJECTIVE: Few studies have examined the effect of perceived social support (PSS) on chemotherapy-related symptoms (CRS). This study examined the effect of PSS on CRS in 184 patients with breast cancer. METHODS: Participants were consecutively enrolled from a tertiary general hospital in Seoul, South Korea. CRS were assessed eight times, from before the first neoadjuvant chemotherapy to six months after the end of neoadjuvant chemotherapy, with the MD Anderson Symptom Inventory. PSS was evaluated once, before the first neoadjuvant chemotherapy session, using the Multidimensional Scale of Perceived Social Support (MSPSS). Two groups were formed based on MSPSS scores: the low PSS group (n = 62) and the moderate-to-high PSS group (n = 122). Linear mixed model analyses were used to compare the change in CRS severity between the two groups during chemotherapy. RESULTS: Results indicated a significant group-by-time (low PSS or moderate-to-high PSS; 8 periods of chemotherapy) interaction for pain (p = .005), nausea (p = .033), insomnia (p < .001), distress (p = .003), dyspnea (p = .014), memory loss (p = .021), vomiting (p = .016), and numbness (p = .008) in which the moderate-to-high PSS group showed significantly lower levels of increase in those symptoms during chemotherapy. Moreover, the effect of PSS on CRS differed depending on the sources of PSS. CONCLUSION: Patients with moderate-to-high PSS experience less severe CRS compared with patients with low PSS during chemotherapy. The current findings indicate the potential benefits of providing social support in the management of CRS.

Morning chronotype is a protective factor against chemotherapy-induced hot flashes in premenopausal women with breast cancer.

PURPOSE: Adjuvant chemotherapy in patients with breast cancer often causes hot flashes, impairing quality of life. However, the chronobiological or psychiatric factors associated with the development of chemotherapy-induced hot flashes (CIHFs) remain undetermined. The purpose of this study was to investigate whether chronotype was associated with the incidence of CIHFs. METHODS: A total of 119 premenopausal women with non-metastatic breast cancer awaiting adjuvant chemotherapy after surgery without hot flashes were included. The presence of CIHF was defined as having moderate to severe hot flashes, as measured by the subscale of hot flashes in the Menopause Rating Scale, at 4 weeks after the completion of chemotherapy. Chronotype (Morning/Intermediate/Evening) was assessed with the Composite Scale of Morningness before adjuvant chemotherapy. To examine the association between chronotype and CIHF, we built logistic regression models, adjusting for age, body mass index, sleep quality, and radiation therapy. RESULTS: CIHF occurred in 50.4% of participants. Morning type was inversely associated with CIHF (reference: Intermediate type, odds ratio [OR], 0.37; 95% confidence interval [CI], 0.16-0.94; p = 0.040) in the univariate model, and the association remained significant (OR, 0.37; CI, 0.13-0.96; p = 0.045) after adjusting for age, body mass index, sleep quality, and radiation therapy. CONCLUSIONS: Morning chronotype is a protective factor against the development of CIHF in patients with breast cancer. Chronotypes should be assessed and considered in the prediction and management of CIHF.

Trajectory of severity of postoperative delirium symptoms and its prospective association with cognitive function in patients with gastric cancer: results from a prospective observational study.

PURPOSE: Delirium is a common neurocognitive complication in cancer. Despite this, the studies examining the trajectory of the severity of delirium symptoms and its impact on health outcome in gastric cancer is rather limited. This study examined the trajectory of delirium symptom severity (DSS) following resection surgery for gastric cancer and its prospective association with cognitive function. METHODS: A three-wave prospective observational study was conducted with 242 gastric cancer patients admitted for resection surgery at a teaching hospital in South Korea from May 2016 to November 2017. DSS was assessed by the clinical staff before and 1, 2, 3, and 7 days after surgery using the Delirium Rating Scale-Revised-98. A survey including the Functional Assessment of Cancer Therapy-Cognitive Scale (FACT-Cog) and Mini-Mental State Examination (MMSE) was administered before surgery (T0), 7 days after (T1), and 3 to 6 months after surgery (T2). RESULTS: Out of 242 participants, 48.8% (118) completed the survey at all three time points, 43.4% (105) did so for two time points, and 7.9% (19) for one time point. No cases of full delirium were observed over four postoperative time points. Latent growth curve modeling analyses indicated that DSS declined over 3 days after surgery. Age and anesthesia time were positively associated with the initial level of DSS. A medication history for memory complaints was related to a slower recovery from delirium symptoms. While the use of propofol as an anesthetic agent was associated with lower initial DSS, it predicted a slower recovery from DSS. A higher initial DSS predicted a lower T1 MMSE score. CONCLUSIONS: Severity of postoperative delirium symptoms predicts a short-term and objective cognitive function post-surgery. Monitoring and timely treatment of postoperative delirium symptoms is needed to diminish cognitive consequences in gastric cancer patients.

Delirium and its consequences in the specialized palliative care unit: Validation of the Korean version of Memorial Delirium Assessment Scale.

OBJECTIVES: Delirium is highly prevalent in patients with advanced cancer. This study aimed to investigate delirium rates and potential associated factors such as mortality in patients admitted to an acute palliative care unit (APCU). Our second aim was to validate the Korean version of the Memorial Delirium Assessment Scale (K-MDAS). METHODS: A total of 102 patients with advanced cancer, and who were admitted to the APCU, were assessed. Demographic data were collected alongside clinical diagnosis, Eastern Cooperative Oncology Group (ECOG) performance status, clinical symptoms according to the Edmonton Symptom Assessment System, history of smoking, alcohol use, hypnotic use, and daily dose of morphine were collected. The Confusion Assessment Method, the Delirium Rating Scale-Revised 98, and the K-MDAS were measured at admission and 1 week later. RESULTS: Twenty-four patients (23.52%) were diagnosed with delirium, and associated factors were old age (P = 0.007), higher ECOG (P = 0.011), and drowsiness (P < 0.001). The presence of delirium was an independent predictor of 1-month mortality; male gender, higher body mass index, and hypnotic use were also related to 1-month mortality. The K-MDAS had reliable internal consistency (α = 0.942) and showed sensitivity of 0.958 and specificity of 0.921 at the optimal cutoff score for diagnosing delirium of 9. CONCLUSIONS: Delirium was prevalent in patients admitted to the APCU and was associated with 1-month mortality. The K-MDAS showed acceptable reliability and validity and can be used to screen for delirium in a palliative care setting.

Incidence and risk factors of subsyndromal delirium after curative resection of gastric cancer.

BACKGROUND: Subsyndromal delirium, a condition in which patients exhibit some, but not all, of the symptoms of delirium, can negatively affect the outcomes of patients with cancer. However, the incidence of subsyndromal delirium in patients with gastric cancer is unknown. Here, we investigated the incidence and risk factors of subsyndromal delirium after curative resection of gastric cancer. METHODS: We recruited consecutive patients with gastric cancer who were scheduled for curative resection at a tertiary hospital. Patients' subsyndromal delirium symptoms were serially assessed preoperatively and 1, 2, 3, and 7 days postoperatively using the Delirium Rating Scale-Revised-98 (DRS-R-98). A DRS-R-98 score of 8-14 at any postoperative assessment was considered to indicate subsyndromal delirium. Sociodemographic and pre-/intra-operative clinical data were also assessed. Logistic regression analyses were used to determine the associated risk factors. RESULTS: Data were analysed from 163 out of 217 eligible patients. Postoperative delirium occurred in one patient (0.6%) and subsyndromal delirium occurred in 19 patients (11.7%). Age ≥ 70 years (odds ratio, [OR] 3.85; 95% confidence interval [CI], 1.36-10.92; p = 0.011) and education level ≤ 9 years (OR, 3.98; 95% CI, 1.39-11.41; p = 0.010) were independent risk factors of subsyndromal delirium after adjusting for preoperative cognitive function. Other pre-/intra-operative variables including anxiety/depression, poor sleep quality, and anaesthesia duration were not associated with subsyndromal delirium. CONCLUSIONS: In contrast to the low incidence of delirium among patients undergoing curative resection of gastric cancer, a substantial proportion of such patients experienced subsyndromal delirium. Considering the prognostic implications, more careful detection and management of subsyndromal delirium may be warranted in patients with gastric cancer.

Temporal trajectory of quality of life and its predictors in recipients of hematopoietic stem cell transplantation.

This prospective longitudinal study evaluated the temporal trajectory of health-related quality of life (HRQOL) and its associated factors in patients who received hematopoietic stem cell transplantation (SCT) 6 months after transplantation. Eighty-nine adult patients who were admitted to Seoul National University Hospital for SCT were consecutively included in the study. The participants completed three standardized questionnaires: Insomnia Severity Index, Hospital Anxiety and Depression Scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The participants completed the study questionnaires at three time points: before SCT (T1), immediately after SCT (T1), and 6 months after SCT (T3). Immediately after SCT, HRQOL decreased significantly (p < 0.001), followed by recovery over 6 months. The conditioning regimen for SCT showed no correlation with HRQOL at T2 (p = 0.283) or T3 (p = 0.799), with no significant difference in HRQOL between allogeneic and autologous SCT recipients at T2 (p = 0.829) or T3 (p = 0.824). Depression (p = 0.042), pain (p = 0.023), and appetite loss (p = 0.004) negatively influenced HRQOL at T1, whereas only pain (p = 0.048) remained an important factor at T2. Six months after SCT, the two most frequent symptoms, fatigue and financial problems, became major factors (p = 0.004 and p = 0.005, respectively). Depression began to play an important role in HRQOL again at T3 (p = 0.040). These findings demonstrate that SCT recipients need both psychological and medical support to achieve a better HRQOL after SCT.

Pre-treatment anxiety is associated with persistent chemotherapy-induced peripheral neuropathy in women treated with neoadjuvant chemotherapy for breast cancer.

OBJECTIVE: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse reaction caused by chemotherapeutic agents, especially the taxanes. CIPN can persist from months to years after completion of chemotherapy, decreasing quality of life for cancer survivors. The aim of this study was to explore the incidence and risk factors of persistent CIPN among women with breast cancer receiving neoadjuvant chemotherapy. METHODS: In this prospective study, we recruited women with breast cancer receiving neoadjuvant chemotherapy, including four cycles of docetaxel. Participants reported neuropathic symptoms of tingling/numbness at baseline, at the end of chemotherapy treatment, and at 8 months after completion of chemotherapy. Candidate factors associated with CIPN were assessed before chemotherapy. RESULTS: Among 111 participants, 50 (45.0%) experienced CIPN during chemotherapy, and 21 (18.9%) reported persistent CIPN after chemotherapy. Univariate logistic regression analysis revealed that development of CIPN was significantly associated with pre-treatment numbness (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.09-7.40; p = .033), and persistent CIPN was significantly associated with pre-treatment numbness (OR, 3.60; 95% CI, 1.12-11.61; p = .032) and pre-treatment anxiety (OR, 5.02; 95% CI, 1.84-13.70; p = .002). Multivariate analysis indicated that pre-treatment anxiety remained significantly associated with persistent CIPN (OR, 4.01; 95% CI, 1.25-12.87; p = .020). CONCLUSION: Our results suggested that pre-treatment anxiety might be related to a patient's risk for persistent CIPN in women with breast cancer undergoing neoadjuvant chemotherapy. Further research is required to investigate if interventions targeting pre-treatment anxiety could provide prevention and management for persistent CIPN.