Impact of the COVID-19 Pandemic on Outcomes and Perioperative Factors Associated with Posterior Cervical Fusion.

Introduction: While there is anecdotal evidence that the coronavirus disease 2019 (COVID-19) pandemic altered perioperative decision-making in patients requiring posterior cervical fusion (PCF), a national-level analysis to examine the significance of this hypothesis has not yet been conducted. This study aimed to determine the potential differences in perioperative variables and surgical outcomes of PCF performed before vs. during the COVID-19 pandemic. Methods: Adults who underwent PCF were identified in the 2019 (prepandemic) and 2020 (intrapandemic) NSQIP datasets. Differences in 30-day readmission, reoperation, and morbidity were evaluated using multivariate logistic regression. On the other hand, differences in operative time and relative value units (RVUs) were estimated using quantile regression. Furthermore, the odds ratios (OR) for length of stay (LOS) were estimated using negative binomial regression. Secondary outcomes included rates of nonhome discharge and outpatient surgery. Results: A total of 3,444 patients were included in this study (50.7% from 2020). Readmission, reoperation, morbidity, operative time, and RVUs per minute were similar between cohorts (p>0.05). The LOS (OR 1.086, p<0.001) and RVUs-per-case (coefficient +0.360, p=0.037) were significantly greater in 2020 compared to 2019. Operation year 2020 was also associated with lower rates of nonhome discharge (22.3% vs. 25.8%, p=0.017) and higher rates of outpatient surgery (4.8% vs. 3.0%, p=0.006). Conclusions: During the COVID-19 pandemic, a 28% decreased odds of nonhome discharge following PCF and a 72% increased odds of PCF being performed in an outpatient setting were observed. The readmission, reoperation, and morbidity rates remained unchanged during this period. This is notable given that patients in the 2020 group were more frail. This suggests that patients were shifted to outpatient centers possibly to make up for potentially reduced case volume, highlighting the potential to evaluate rehabilitation-discharge criteria. Further research should evaluate these findings in more detail and on a regional basis.

What is a better value for your time? Anterior cervical discectomy and fusion versus cervical disc arthroplasty.

Introduction: Compared to anterior cervical discectomy and fusion (ACDF), the motion preservation of cervical disc arthroplasty (CDA) provides an attractive alternative with similar short-term results. However, there is a paucity of the economics of performing CDA over ACDF. Study Design: This was retrospective study. Objective: The objective of this study is to evaluate relative-value-units (RVUs), operative time, and RVUs-per-minute between single-level ACDF and CDA. Secondary outcomes included 30-day readmission, reoperation, and morbidity. Methods: Adults who underwent ACDF or CDA in 2011-2019 National Surgical Quality Improvement Program database datasets. Multivariate quantile regression was utilized. Results: There were 26,595 patients (2024 CDA). ACDF patients were older, more likely to be female, discharged to inpatient rehabilitation, and have a history of obesity, smoking, diabetes, steroid use, and the American Society of Anesthesiologists-class ≥3. ACDF had greater median RVUs-per-case (41.2 vs. 24.1) and RVUs-per-minute (0.36 vs. 0.27), despite greater operative-time (109 min vs. 92 min) (P < 0.001). ACDF predicted a 16.9 unit increase in median RVUs per case (P < 0.001, confidence interval [CI]95: 16.3-17.5), an 8.81 min increase in median operative time per case (P < 0.001, CI95: 5.69-11.9), and 0.119 unit increase in median RVUs-per-minute (P < 0.001, CI95: 0.108-0.130). ACDF was associated with greater unadjusted rates of readmission (3.2% vs. 1.4%) morbidity (2.3% vs. 1.1%) (P < 0.001), but similar rates of reoperation (1.3% vs. 0.8%, P = 0.080). After adjusting for significant patient-related and procedural factors, readmission (odds ratio [OR] = 0.695, P = 0.130, CI95: 0.434-1.113) and morbidity (OR = 1.102, P = 0.688, CI95: 0.685-1.773) was similar between ACDF and CDA. Conclusions: Median RVUs-per-minute increased by 0.119 points for ACDF over CDA, or $257.7/h for each additional-hour of surgery. Adjusted 30-day outcomes were similar between procedures. Reimbursement for CDA does not appear to be in line with ACDF and may be a barrier to widespread usage.

Liposomal bupivacaine does not decrease postoperative opioid use or length of hospital stay in patients undergoing anterior cervical discectomy and fusion.

Background: Despite its widespread use, definitive data demonstrating the efficacy of liposomal bupivacaine (LB) is limited especially in patients undergoing anterior cervical discectomy and fusion (ACDF). Therefore, this investigation examined whether ACDF patients who received intra-operative LB (LB cohort) exhibited decreased post-operative opioid use and lengths of hospital stay (LOS) compared to ACDF patients who did not receive intra-operative LB (controls). Methods: Eighty-two patients who underwent primary ACDF by a single surgeon from 2016 to 2019 were identified from an institutional database. Fifty-nine patients received intra-operative LB while twenty-three did not. Patient characteristics, medical comorbidities, complications, post-operative opioid consumption, and LOS data were collected. Results: The LB cohort did not require fewer opioids on post-operative day (POD) 0, POD1, POD2, or throughout the hospital course after normalizing by LOS (total per LOS). The number of cervical vertebrae involved in surgery, but not LB use, predicted opioid consumption on POD0, POD1, and total per LOS. For every vertebral level involved, 242 additional morphine milligram equivalents (MME) were consumed on POD0, 266 additional MME were utilized on POD1, and 130 additional MME were consumed in total per LOS. Conclusions: ACDF patients who received intra-operative LB did not require fewer post-operative opioids or exhibit a decreased LOS compared to controls. Patients whose procedures involved a greater number of cervical vertebrae were associated with greater opioid consumption on POD0, POD1, and total per LOS. ACDF patients, especially those who had a high number of vertebrae involved, may require alternative analgesia to LB.

Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy.

Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology.

Cancer Supportive and Survivorship Care in Singapore: Current Challenges and Future Outlook.

Despite being a relatively young nation, Singapore has established itself as a leading multifaceted medical hub, both regionally and globally. Although Singapore continues to pursue excellence in oncology care, cancer supportive care and survivorship care remain in the infancy stage. In an effort to advance this important aspect of oncology care in Singapore, the first cancer supportive and survivorship care forum was held in December 2016, involving 74 oncology practitioners. The primary goals of this forum were to raise awareness of the importance of cancer supportive and survivorship care and to provide a platform for oncology practitioners of diverse backgrounds to converge and address the challenges associated with the delivery of cancer supportive and survivorship care in Singapore. Key challenges identified during this forum included, but were not limited to, care fragmentation in an oncologist-centric model of care, poor integration of allied health and rehabilitation services, passive engagement of community partners, lack of specialized skill sets and knowledge in supportive and survivorship care, and patient-related barriers such as poor health literacy. The survivorship care model commonly used in Singapore places an imbalanced emphasis on surveillance for cancer recurrence and second primary cancers, with little attention given to the supportive and survivorship needs of the survivors. In summary, these challenges set the stage for the development and use of a more survivor-centric model, one that focuses not only on cancer surveillance, but also on the broad and unique physical and psychosocial needs of survivors of cancer in Singapore.

Impact of Adjuvant Anthracycline-Based and Taxane-Based Chemotherapy on Plasma VEGF Levels and Cognitive Function in Breast Cancer Patients: A Longitudinal Study.

BACKGROUND: Vascular endothelial growth factor (VEGF) has been shown to induce neurogenesis in the brain and yield neuroprotective effects. It is hypothesized that chemotherapy reduces circulating VEGF levels and leads to cognitive decline among patients. This multicenter longitudinal study aimed to evaluate the impact of chemotherapy on VEGF levels and the association between VEGF levels and cognitive function. PATIENTS AND METHODS: A total of 145 early-stage breast cancer patients were recruited and assessed before chemotherapy (T1), during chemotherapy (T2), and at the end of chemotherapy (T3). At each time point, plasma VEGF levels were assessed using a multiplex immunoassay. Cognitive function was assessed using both Functional Assessment of Cancer Therapy-Cognitive Function, Version 3 (FACT-Cog), and Headminder (a computerized, web-based neuropsychologic battery). RESULTS: Generally, we observed higher-than-baseline plasma VEGF levels after the start of chemotherapy (P < .001). Among patients receiving anthracycline-based chemotherapy, the median plasma VEGF levels were significantly higher at T2 (T2: 37.3 pg/mL vs. T1: 21.3 pg/mL; P < .001) and T3 (T3: 35.5 pg/mL vs. T1: 21.3 pg/mL; P < .001) than at baseline. Plasma VEGF levels were not associated with chemotherapy-associated cognitive impairment. CONCLUSION: Breast cancer patients experience an increasing trend in plasma VEGF levels during chemotherapy, and the regimen types may have a differential effect on circulating VEGF levels. Furthermore, changes in plasma VEGF levels during chemotherapy were not associated with cognitive impairment. VEGF may play a minor role in mediating the occurrence of chemotherapy-associated cognitive impairment.

Survivorship care models for breast cancer, colorectal cancer, and adolescent and young adult (AYA) cancer survivors: a systematic review.

BACKGROUND: Well-elucidated survivorship care models are pertinent in the long-term management of cancer survivors. This review aims to update existing literature and evaluate the key components of such models with a focus on breast, colorectal, and adolescent and young adult (AYA) cancer survivors. METHODS: The PubMed electronic database were searched comprehensively for relevant publications in English through February 2017. Additional manual searches were conducted for reference lists and official guidelines published by oncology societies. Included studies addressed the correct cancer type, elaborated on each model's structure and provided patient-related outcome data to support its model's effectiveness if applicable. RESULTS: Among the 25 included studies, six articles described survivorship models applicable to all cancer types, and the remaining focused on breast cancer (n = 10), colorectal cancer (n = 3), and AYA cancer survivors (n = 6). Shared-care model was largely described for all cancer types whereas multidisciplinary model predominated for AYA cancer survivors. Upon evaluation, these models described the essential components of survivorship care fairly well except for the care coordination component. Also, the definition of time points of care was vague and noncomprehensive. CONCLUSION: The reviewed survivorship model studies were comprehensive but were limited by a lack of existing rigorous evaluation efforts to assess their effectiveness. This review further provided valuable recommendations for future methodological evaluation of such models. This review has highlighted care coordination as an area for improvement and emphasized the importance of obtaining data on the effectiveness of these survivorship models to ensure satisfactory quality of life and health outcomes.

Distinct and heterogeneous trajectories of self-perceived cognitive impairment among Asian breast cancer survivors.

OBJECTIVES: Currently, there are no studies that have established the self-perceived cognitive trajectories experienced by breast cancer patients (BCPs) post-chemotherapy. Therefore, we characterized the long-term trajectory of self-perceived cognitive function among Asian early-stage BCPs using the minimal clinically important difference of a subjective measure of cognitive function. METHODS: Early-stage BCPs who received chemotherapy were recruited and assessed at 4 time points: Before chemotherapy initiation (T1), 6 weeks post-chemotherapy initiation (T2), 12 weeks post-chemotherapy initiation (T3), and 15-months post-chemotherapy initiation (T4). All assessments were performed approximately within 2 weeks post-chemotherapy. Subjective and objective cognitive function were assessed using Functional Assessment of Cancer Therapy-Cognitive (version 3) and Headminder™. RESULTS: A total of 166 BCPs were recruited, of whom 131 completed assessment at all time points. Using the minimal clinically important difference of Functional Assessment of Cancer Therapy-Cognitive, 5 distinct cognitive trajectories were established. Of the 131 patients, 70 (53.4%) did not report any clinically significant cognitive impairment. Twenty-one (16.0%) patients reported acute cognitive changes during chemotherapy (T2 and/or T3) but not at T4. Forty patients (30.5%) reported clinically significant cognitive impairment at T4, of whom 18 did not report any cognitive impairment at earlier time points. Fifteen (11.5%) patients reported persistent cognitive impairment throughout all time points, while 7 (5.3%) patients reported intermittent cognitive impairment at T2 and T4 but not at T3. CONCLUSION: This is the first study to establish the existence of heterogeneous cognitive trajectories based on clinically significant thresholds of self-perceived cognitive impairment. The findings have important implications on the window for screening and management of post-chemotherapy cognitive impairment.

Association of mitochondrial DNA content in peripheral blood with cancer-related fatigue and chemotherapy-related cognitive impairment in early-stage breast cancer patients: a prospective cohort study.

PURPOSE: Cancer-related fatigue (CRF) and chemotherapy-related cognitive impairment (CRCI) are reported to be associated with mitochondrial dysfunction. Hence, mitochondrial DNA (mtDNA) content, a biomarker of mitochondrial dysfunction, is hypothesized to correlate with the onset of CRF and CRCI. This study aims to evaluate the association between peripheral blood mtDNA content reduction and severity of CRF and CRCI in patients receiving chemotherapy. METHODS: This was a prospective cohort study. Early-stage breast cancer patients receiving anthracycline- or taxane-based chemotherapy were recruited. CRF was assessed using MFSI-SF, and CRCI was assessed using FACT-Cog and CANTAB at two timepoints: baseline (T1; prior to treatment) and 6 weeks after initiation of treatment (T2). mtDNA content was measured at both timepoints using real-time quantitative polymerase chain reaction. Multiple logistic regression was utilized to evaluate the association between mtDNA reduction and worsening of CRF and CRCI, adjusting for age, anxiety, insomnia, plasma cytokines concentrations, and other clinically important covariates. RESULTS: A total of 108 patients (age 52.0 ± 9.2 years; 82.4% Chinese; 64.8% receiving anthracycline-based chemotherapy) were recruited. Proportions of patients with worsening of CRF increased from the lower to the upper quartiles of mtDNA reduction (22.2, 33.3, 55.6, and 63.0% in quartiles 1, 2, 3, and 4, respectively, p = 0.001 for trend). Reduction of mtDNA content was significantly greater among those with worsening of CRF and CRCI compared to those without CRF [mean reduction (± SD): 36.5 (46.1) vs. 9.4 (34.5), p < 0.001]. After adjusting for covariates, every 1-unit reduction of the mtDNA content was associated with a 4% increased risk for worsening of CRF (95% CI, 1-6%; p = 0.009). CONCLUSIONS: This is the first study to show that the reduction of mtDNA content in peripheral blood is associated with the onset of CRF in patients receiving chemotherapy. Further validation studies are required to confirm the findings.

Psychometric properties and measurement equivalence of the Multidimensional Fatigue Syndrome Inventory- Short Form (MFSI-SF) amongst breast cancer and lymphoma patients in Singapore.

BACKGROUND: Currently, several fatigue measurement instruments are available to evaluate and measure cancer-related fatigue. Amongst them, Multidimensional Fatigue Syndrome Inventory-Short Form (MFSI-SF) is a self-reported instrument and a multidimensional scale that aims to capture the global, somatic, affective, cognitive and behavioural symptoms of fatigue. This study examines the psychometric properties and measurement equivalence of the English and Chinese versions of MFSI-SF in breast cancer and lymphoma patients in Singapore. METHODS: Patients were recruited from National Cancer Centre Singapore. Validity, reliability and responsiveness of MFSI-SF were evaluated in this study. Convergent validity was evaluated by correlating total and subscales of MFSI-SF to known related constructs in EORTC QLQ-C30. Known group validity was assessed based on patients' cancer stage, pain, insomnia and depression symptoms. Reliability was evaluated by Cronbach's α. Responsiveness analyses were performed with patients who have undergone at least one cycle of chemotherapy. Multiple regression was used to compare the total and subscale scores of MSFI-SF between the two language versions. RESULTS: Data from 246 (160 English and 86 Chinese version) breast cancer and lymphoma patients were included in the study. Moderate to high correlations were observed between correlated MFSI-SF subscales and EORTC QLQ-C30 domains (|r| = 0.524 to 0.774) except for a poor correlation (r = 0.394) observed between MFSI-SF vigour subscale and EORTC QLQ-C30 role functioning subscale. Total MFSI-SF scores could differentiate between patients with higher depression, pain and insomnia status. Internal consistency of MFSI-SF was also high (α = 0.749 to 0.944). Moderate correlation was observed between change in total MFSI-SF score and change in fatigue symptom scale score and global QoL score on EORTC QLQ-C30 (|r| = 0.478 and 0.404 respectively). Poor correlations were observed between change in scores of hypothesised subscales (|r| = 0.202 to 0.361) except for a moderate correlation between change in MFSI-SF emotional fatigue score and change in EORTC QLQ-C30 emotional functioning domain score. Measurement equivalence was established for all subscales and total MFSI-SF score except for the emotional and vigour subscales. CONCLUSIONS: This study supports the use of MFSI-SF as a reasonably valid scale with good internal consistency for measuring fatigue levels in the Singapore cancer population.

Practitioners' perspectives on community-based breast cancer survivorship care in Singapore: A focus group study.

With the long-term goal of optimising the delivery of breast cancer survivorship care in Singapore, we conducted a qualitative study to gather in-depth descriptions from community practitioners (general practitioners and community pharmacists) about their perceptions of community-based cancer survivorship care in Singapore. Sixteen participants (11 general practitioners and five community pharmacists) participated in four structured focus group discussions between August and November 2016. The focus group discussions were analysed using deductive content analysis. The majority of community practitioners do not encounter breast cancer survivors in their clinical practices. Perceived barriers to community-based survivorship care include patients' lack of confidence in primary care, financial constraints and lack of empanelment. Most community practitioners concur that the success of community-based survivorship care largely depends on the co-operation and participation of survivors. Survivorship management via standardised care pathways is not fully advocated by practitioners. Survivorship care plans are identified as useful, but they should also incorporate a non-cancer-related medical history and medication list. Community practitioners in Singapore are eager to participate in the delivery of cancer survivorship care. Future studies should develop a community-based care model that involves community practitioners and evaluate the cost-effectiveness of such a care model. The current model of cancer survivorship in Singapore is not sustainable. Differences in healthcare ecosystems, cultures and resources available in an Asian context should be taken into consideration before designing a community-based cancer survivorship program in Singapore.

Minimal Clinically Important Difference of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) for Fatigue Worsening in Asian Breast Cancer Patients.

CONTEXT: The minimal clinically important difference (MCID) of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), a questionnaire that measures cancer-related fatigue, has not been established in patients with cancer. OBJECTIVES: This study aims to determine the MCID of the MFSI-SF. METHODS: Breast cancer patients completed the MFSI-SF and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) before chemotherapy and at least three weeks later. The EORTC-QLQ-C30 fatigue scale (EORTC-FA) was used as an anchor, and a receiver operating characteristic (ROC) curve was also used to identify the optimal MCID cut-off for fatigue deterioration. A distribution-based approach used one-third of the SD, half of the SD, and one SEM of the total MFSI-SF score to determine the MCID. RESULTS: A total of 201 patients were analyzed. Change scores of the MFSI-SF and EORTC-FA were moderately correlated (r = 0.47, P < 0.001). The EORTC-FA-anchored MCID was 8.69 points (95% CI: 4.03-13.34). The MCID attained from the ROC curve method was 4.50 points (sensitivity: 68.8%; specificity: 64.1%). For the distribution-based approach, the MCIDs corresponding to one-third of the SD, half of the SD, and one SEM were 5.39, 8.99, and 10.79 points, respectively. CONCLUSION: The MCID of the MFSI-SF identified by all approaches ranged from 4.50 to 10.79 points. The MCID can be used to interpret the clinical significance of fatigue deterioration in patients with breast cancer and to determine sample sizes for future clinical trials.

Evaluation of plasma brain-derived neurotrophic factor levels and self-perceived cognitive impairment post-chemotherapy: a longitudinal study.

BACKGROUND: Preliminary evidence suggests that changes in plasma brain-derived neurotrophic factor (BDNF) levels may contribute to the occurrence of chemotherapy-associated cognitive impairment (CACI), and a previous study suggested that carriers of the BDNF Met homozygous genotype are protected from CACI. METHODS: This multicenter, prospective cohort study involved chemotherapy-receiving early-stage breast cancer (ESBC) patients. Self-perceived cognitive function was longitudinally assessed using the validated FACT-Cog (ver. 3) across three time points: Prior to chemotherapy (T1), during chemotherapy (T2), and at the end of chemotherapy (T3). Plasma BDNF levels were quantified using enzyme-linked immunosorbent assay. Genotyping was performed using Sanger Sequencing. RESULTS: A total of 51 chemotherapy-receiving ESBC patients (mean age: 52.6 ± 9.5 years) were recruited, and 11 patients (21.6%) reported subjective cognitive impairment post-chemotherapy. Overall, there was a reduction in median plasma BDNF levels over time (T1: 5423.0 pg/ml; T2: 5313.6 pg/ml; T3: 4050.3 pg/ml; p < 0.01). After adjusting for confounding factors, longitudinal analysis revealed that BDNF levels were associated with self-reported concentration deficit (p = 0.032). Carriers of Val/Val (p = 0.011) and Val/Met (p = 0.003) BDNF genotypes demonstrated a significant reduction in plasma BDNF levels over time; however, plasma BDNF levels were similar across all time points among Met homozygous carriers (p = 0.107). CONCLUSION: There was a statistically significant change in BDNF levels post-chemotherapy in ESBC patients, and plasma BDNF levels were associated with self-perceived concentration deficit in patients receiving chemotherapy.

Perceptions and Barriers of Survivorship Care in Asia: Perceptions From Asian Breast Cancer Survivors.

PURPOSE: With the long-term goal to optimize post-treatment cancer care in Asia, we conducted a qualitative study to gather in-depth descriptions from multiethnic Asian breast cancer survivors on their perceptions and experiences of cancer survivorship and their perceived barriers to post-treatment follow-up. METHODS: Twenty-four breast cancer survivors in Singapore participated in six structured focus group discussions. The focus group discussions were voice recorded, transcribed verbatim, and analyzed by thematic analysis. RESULTS: Breast cancer survivors were unfamiliar with and disliked the term "survivorship," because it implies that survivors had undergone hardship during their treatment. Cognitive impairment and peripheral neuropathy were physical symptoms that bothered survivors the most, and many indicated that they experienced emotional distress during survivorship, for which they turned to religion and peers as coping strategies. Survivors indicated lack of consultation time and fear of unplanned hospitalization as main barriers to optimal survivorship care. Furthermore, survivors indicated that they preferred receipt of survivorship care at the specialty cancer center. CONCLUSION: Budding survivorship programs in Asia must take survivor perspectives into consideration to ensure that survivorship care is fully optimized within the community.

A culturally adapted survivorship programme for Asian early stage breast cancer patients in Singapore: A randomized, controlled trial.

BACKGROUND: As cancer mortality rates improve in Singapore, there is an increasing need to improve the transition to posttreatment survivorship care. This study aimed to evaluate the effectiveness of a psychoeducation group (PEG) intervention program compared with usual care to reduce distress for physical symptom and psychological aspects in Asian breast cancer survivors who have completed adjuvant chemotherapy. METHODS: This was a randomized, controlled trial comprising 72 Asian early stage breast cancer survivors who were randomized into the PEG (n = 34) or the control (n = 38) arm. The participants in the PEG arm underwent a weekly multidisciplinary PEG program delivered in a group format over 3 weeks coupled with cultural adaptation. Both arms were assessed at baseline and 2 months after intervention using the Rotterdam Symptom Checklist, Beck Anxiety Inventory, and EORTC QLQ-C30. A satisfaction questionnaire was also conducted among those survivors who have participated in the PEG program. Effective sizes were calculated using Cohen d. RESULTS: The mean age ± SD of all participants was 53.0 ± 8.9 years, with the majority being Chinese (84.7%) and Malay (6.9%), and clinical characteristics were well balanced in both arms. Compared to the control arm, the PEG arm showed a significantly greater reduction in physical symptom distress (d = 0.76, P = .01) and fatigue (d = 0.49, P = .04). The 82.4% of the participants in the intervention group responded to the satisfaction questionnaire, and the majority (92.9%) agreed that the overall duration of the PEG intervention program was appropriate. CONCLUSIONS: A culturally adapted PEG program was effective in reducing physical symptom distress in Asian breast cancer survivors. (ClinicalTrials.gov: NCT02600299).

Psychometric properties and measurement equivalence of the English and Chinese versions of the Beck Anxiety Inventory in patients with breast cancer.

BACKGROUND: There is a lack of psychometric data for both the English and Chinese versions of Beck Anxiety Inventory (BAI) to support its usage among breast cancer patients. This study examined the psychometric properties and measurement equivalence of the English and Chinese versions of BAI among breast cancer patients in Singapore. METHODS: Patients were recruited from two major cancer centers in Singapore. The criterion and construct validity of BAI was assessed by its correlation strength with (1) the emotional functioning subdomain of EORTC QLQ-C30 and (2) constructs related to anxiety, namely fatigue, dyspnea, and quality of life. The known-group validity was assessed according to the patients' breast cancer stage, religious beliefs, and emotional functioning levels. The internal consistency of the BAI domains was evaluated using Cronbach's alpha coefficient. Regression analysis was performed to compare the BAI total and domain scores between the two language versions. RESULTS: Data from 244 patients (144 English-speaking and 100 Chinese-speaking) were analyzed. For both language versions, the BAI total scores correlated moderately with the EORTC QLQ-C30 emotional functioning subdomain (r = -0.655 and -0.601). Correlations with fatigue, quality of life, and dyspnea were moderate (|r| = 0.456-0.606). Patients with poorer emotional functioning reported higher anxiety levels, establishing known-group validity. All BAI domains demonstrated satisfactory internal consistencies (α = 0.74-0.87), except for the panic domain (α = 0.57-0.61). Possible measurement equivalence between the language versions was established. CONCLUSION: Both English and Chinese versions of BAI are valid, reliable, and possibly equivalent for future use.

Impact of TNF-α (rs1800629) and IL-6 (rs1800795) Polymorphisms on Cognitive Impairment in Asian Breast Cancer Patients.

OBJECTIVE: Expression of pro-inflammatory cytokines is influenced by single nucleotide polymorphisms (SNPs) in the promoter regions of the pro-inflammatory cytokine genes, and cytokines are associated with the occurrence of post-chemotherapy cognitive impairment. Hence, the aim of this study was to evaluate the associations between two common pro-inflammatory cytokine gene polymorphisms namely, IL6-174 (rs1800795 G>C) and TNF-308 (rs1800629 G>A), and chemotherapy-associated cognitive impairment (CACI) among Asian early-stage breast cancer patients. In addition, the differential effect of these SNPs on plasma IL-6 and TNF-α levels, and the associations of plasma IL-6 and TNF-α levels with CACI were also assessed. METHODS: Asian early-stage breast cancer patients (Stage I to III) receiving chemotherapy were prospectively recruited from two cancer centers in Singapore. Patients' cognitive function was longitudinally assessed using the validated FACT-Cog (ver. 3) and an objective computerized battery, Headminder™ at three-time points. Plasma IL-6 and TNF-α levels were analyzed using the multiplex immunoassay, and genotyping was performed using Sanger sequencing. Regression analyses and generalized estimating equation were utilized for statistical analysis. RESULTS: A total of 125 patients were included (mean age: 50.3; Chinese: 80.8%; post-menopausal: 48.0%; 68.0% received anthracycline-based chemotherapy). 36.8% patients experienced self-perceived cognitive impairment, detected in memory (32.8%) and attention (34.2%) domains. Patients with higher levels of anxiety (p<0.001) and insomnia (p = 0.003) also reported more self-perceived cognitive impairment. Higher plasma concentrations of IL-6 were associated with greater severity of self-perceived cognitive impairment (p = 0.001). Polymorphisms of cytokine genes were not associated with expression of plasma cytokines. CONCLUSION: Present findings further contribute to the growing evidence that supports the role of the pro-inflammatory cytokine IL-6 in the occurrence of cognitive impairment post-chemotherapy. However, genetic polymorphism of these cytokines did not play a major role to the cytokine fluctuations as well as cognitive impairment in this cohort. With an increasing evidence to support the cytokine hypothesis, future studies should investigate the role of anti-inflammatory agents in mitigating the cognitive impairment associated with chemotherapy.

Impact of chemotherapy on cancer-related fatigue and cytokines in 1312 patients: a systematic review of quantitative studies.

PURPOSE OF REVIEW: Cancer-related fatigue (CRF) is the most common psychosomatic distress experienced by cancer patients before, during and after chemotherapy. Its impact on functional status and Health Related Quality of Life is a great concern among patients, healthcare professionals and researchers. The primary objective of this systematic review is to determine whether the different chemotherapies affect the association of CRF with individual pro- and anti-inflammatory cytokines. The PRISMA statement guideline has been followed to systematically search and screen article from PubMed and Embase. RECENT FINDINGS: This review has examined 14 studies which included a total of 1312 patients. These studies assayed 20 different kinds of cytokines. The cytokines interleukin-6, interleukin-1RA, TGF-ß and sTNF-R2 were associated with CRF in patients receiving anthracycline-based chemotherapy. However, only interleukin-13 was identified in the taxane-based chemotherapy. Similarly, different sets of cytokines were linked with CRF in patients with chemotherapy regimens containing platinum, cyclophosphamides, topotecan or bleomycin. SUMMARY: This review has identified that cytokines are differentially linked with CRF according to the various types of chemotherapy regimens.

Assessment of mental health literacy in patients with breast cancer.

INTRODUCTION: Psychosocial distress is often underdiagnosed and undertreated among breast cancer patients due to the poor recognition of the associated symptoms and inadequate knowledge of the treatments available. OBJECTIVE: To evaluate the mental health literacy of breast cancer patients by assessing (1) their ability to recognize the symptoms of anxiety, fatigue, depression, and cognitive disturbances, and (2) their knowledge of help-seeking options and professional treatments. METHODS: In this multi-center, cross-sectional study, early-stage breast cancer patients receiving chemotherapy underwent four assessments to measure their levels of anxiety, depression, fatigue, and cognitive disturbances. With the aid of cancer-specific vignettes, a questionnaire was administered to evaluate their mental health literacy. RESULTS: Fifty-four patients were recruited (77.7% Chinese, aged 52.7 ± 8.5 years). Clinically significant anxiety (15.1%), fatigue (27.8%), and cognitive disturbances (25.9%) were more prevalent than depression (5.6%). Although the majority of the patients could recognize the symptoms of fatigue accurately (75.9%), less than half could identify those of anxiety (35.2%), depression (48.1%), and cognitive disturbances (48.1%). Patients were more receptive to help from their family members (score: 3.39 out of 4.00) and oncologists (score: 3.13) than from other mental health specialists, such as psychiatrists (score: 2.26) and psychologists (score: 2.19) in the management of their psychosocial distress. Approximately half of the patients indicated that embarrassment and fear were their main barriers to seeking professional treatment (55.6%). CONCLUSIONS: Our results suggest that the mental health literacy of breast cancer patients was inadequate. Intervention and management strategies could be implemented to teach these patients about evidence-based treatments and professional help that are specific to mental disorders.

Medication use by early-stage breast cancer survivors: a 1-year longitudinal study.

PURPOSE: The aim of this study is to characterize the patterns of medication use by early-stage breast cancer (ESBC) survivors from diagnosis to 1 year post-chemotherapy. METHODS: A single-center longitudinal study was conducted with ESBC patients diagnosed between December 2011 and June 2014. Data on the medication use of individual patients were retrieved from prescription databases, supplemented by records from the National Electronic Health Records. The data covered the period from ESBC diagnosis to 1 year post-chemotherapy. Medication types were classified according to the World Health Organization's Anatomical Therapeutic Chemical classification system, and medication for chronic diseases was created by adapting a list of 20 chronic diseases provided by the U.S. Department of Human and Health Services. RESULTS: Of the 107 patients involved in the study (mean age 51.1 ± 8.4 years; 78.5 % Chinese), 46.7 % manifested non-cancer comorbidities, of which hypertension (24.3 %) was the most prevalent, followed by hyperlipidemia (13.1 %) and diabetes (5.6 %). Calcium channel blockers (12.1 %) and lipid-modifying agents (11.2 %) were the most common chronic medication types used before chemotherapy, and their use persisted during chemotherapy (10.3 and 11.2 %, respectively) and after chemotherapy (11.2 and 13.1 %, respectively). Hormonal therapy was the predominant post-chemotherapy medication (77.6 %). A statistically significant increase (p < 0.0001) was observed in the mean number of chronic disease medication classes prescribed to patients between the pre-chemotherapy (0.53 ± 1.04) and chemotherapy (0.62 ± 1.08) periods and between the chemotherapy and post-chemotherapy (1.63 ± 1.35) periods. CONCLUSIONS: There is an increase in trend of chronic medication usage in breast cancer survivors after cancer treatment. This study provides important insights into the design of medication management programs tailored to this population. Future studies should incorporate a control population to improve the interpretation of study results.