Search

Background Given that CRF is characterized by a lack of energy, it is postulated that mitochondrial dysfunction may contribute to its etiology. Using mitochondrial DNA (mtDNA) copy number and displacement-loop (D-loop) mutation status, this study aims to evaluate mtDNA content between fatigue subclasses, over the course of chemotherapy. Methods In a prospective cohort study, early-stage breast patients’ fatigue levels were assessed using the validated Multi-Dimensional Fatigue Symptom Inventory–Short Form (MFSI-SF) and their blood was drawn before, during and after treatment. Relative mtDNA copy number was determined via real-time quantitative polymerase chain reaction while mitochondrial genome was sequenced directly for D-loop mutations at nucleotide positions 303, 489 and 514. Subclasses of extent of fatigue was derived using latent class analysis, based on magnitude of change in sub-domain scores after treatment, with respect to baseline. Clinically relevant factors that differentiate the identified subclasses were then compared between the fatigued groups. Results A total of 133 patients (mean age ± SD: 51.2 ± 8.8 years, median mtDNA: 71.0) were classified into two fatigue subclasses: mild fatigue (75.2%) and fatigued group (24.8%) respectively. Based on mtDNA trajectory, patients who are predisposed to CRF started off with lower baseline values and experienced slower recovery. Median mtDNA content was reduced over 12 weeks after initiation of chemotherapy (p Conclusions mtDNA content and D-loop mutation status do not sufficiently differentiate fatigue subclasses, suggesting that future research may be needed to study the differential expression of mitochondrial dysfunction-related genes and the pathways they may perturb. Legal entity responsible for the study National University of Singapore. Funding National Medical Research Council. Disclosure All authors have declared no conflicts of interest.

Men receiving androgen deprivation therapy (ADT) for prostate cancer (PCa) are likely to develop metabolic conditions such as diabetes, cardiovascular disease, abdominal obesity and osteoporosis. Other treatment-related side effects adversely influence quality of life (QoL) including vasomotor distress, depression, anxiety, mood swings, poor sleep quality and compromised sexual function. The objective of this study was to systematically review the nature and effects of dietary and exercise interventions on QoL, androgen deprivation symptoms and metabolic risk factors in men with PCa undergoing ADT. An electronic search of CINAHL, CENTRAL, Medline, PsychINFO and reference lists was performed to identify peer-reviewed articles published between January 2004 and December 2014 in English. Eligible study designs included randomised controlled trials (RCTs) with pre- and post-intervention data. Data extraction and assessment of methodological quality with the Cochrane approach was conducted by two independent reviewers. Seven exercise studies were identified. Exercise significantly improved QoL, but showed no effect on metabolic risk factors (weight, waist circumference, lean or fat mass, blood pressure and lipid profile). Two dietary studies were identified, both of which tested soy supplements. Soy supplementation did not improve any outcomes. No dietary counselling studies were identified. No studies evaluated androgen-deficiency symptoms (libido, erectile function, sleep quality, mood swings, depression, anxiety and bone mineral density). Evidence from RCTs indicates that exercise enhances health- and disease-specific QoL in men with PCa undergoing ADT. Further studies are required to evaluate the effect of exercise and dietary interventions on QoL, androgen deprivation symptoms and metabolic risk factors in this cohort.

Introduction Previous literature revealed an association between low income and depression. Despite the availability of effective treatments, depression is often underdiagnosed and undertreated. This study was designed to evaluate the prevalence of depressive symptoms and their impact on health-related quality of life (HRQoL) in a low-income population in Macao. Methods This cross-sectional study targeted the adult beneficiaries of local food bank program. The program was established to provide food assistance to the residents who had low income but were ineligible for government financial assistance. All data were collected through interview and questionnaires. The Patient Health Questionnaire (PHQ-9) was used for assessing depressive symptoms. Information about depression diagnosis was obtained by the self-report method. HRQoL levels were measured by the 12-item Short-Form Health Survey, Version 2.0. Results A total of 272 study participants were included for analysis. Based on the PHQ-9 scores, 27.6% of the participants suffered from moderate to severe depressive symptoms. Among them, 76% were not diagnosed with depression. Those with moderate to severe depressive symptoms had significantly lower levels of HRQoL (P

This is one of the largest multicentered, cohort studies conducted to evaluate the proinflammatory biomarkers associated with cognitive impairment in breast cancer patients. While elevated interleukin (IL)-6 and IL-1β were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment., Background Existing evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients. Patients and methods Chemotherapy-receiving breast cancer patients (stages I–III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte–macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder™) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain. Results Ninety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1β was associated with poorer response speed performance (estimate: −0.78; 95% confidence interval (CI) −1.34 to −0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1β and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022). Conclusions While elevated concentrations of IL-6 and IL-1β were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes.

Purpose Cognitive alterations are reported in breast cancer patients receiving chemotherapy. This has adverse effects on patients’ quality of life and function. This systematic review investigates the effectiveness of pharmacologic and non-pharmacologic interventions to manage cognitive alterations associated with breast cancer treatment. Methods Medline via EBSCOhost, CINAHL and Cochrane CENTRAL were searched for the period January 1999 to May 2014 for prospective randomized controlled trials related to the management of chemotherapy-associated cognitive alterations. Included studies investigated the management of chemotherapy-associated cognitive alterations and used subjective or objective measures in patients with breast cancer during or after chemotherapy. Two authors independently extracted data and assessed the risk of bias. Results Thirteen studies involving 1138 participants were included. Overall, the risk of bias for the 13 studies were either high (n=11) or unclear (n=2). Pharmacologic interventions included psychostimulants (n=4), epoetin alfa (n=1), and Ginkgo biloba (n=1). Non-pharmacologic interventions were cognitive training (n=5) and physical activity (n=2). Pharmacologic agents were ineffective except for self-reported cognitive function in an epoetin alfa study. Cognitive training interventions demonstrated benefits in self-reported cognitive function, memory, verbal function and language and orientation/attention. Physical activity interventions were effective in improving executive function and self-reported concentration. Conclusion Current evidence does not favor the pharmacologic management of cognitive alterations associated with breast cancer treatment. Cognitive training and physical activity interventions appear promising, but additional studies are required to establish their efficacy. Further research is needed to overcome methodological shortfalls such as heterogeneity in participant characteristics and non-standardized neuropsychological outcome measures.

PurposeDermatologic adverse events (dAEs) in cancer treatment are frequent with the use of targeted therapies. These dAEs have been shown to have significant impact on health-related quality of life (HRQoL). While standardized assessment tools have been developed for physicians to assess severity of dAEs, there is a discord between objective and subjective measures. The identification of patient-reported outcome (PRO) instruments useful in the context of targeted cancer therapies is therefore important in both the clinical and research settings for the overall evaluation of dAEs and their impact on HRQoL.MethodsA comprehensive, systematic literature search of published articles was conducted by two independent reviewers in order to identify PRO instruments previously utilized in patient populations with dAEs from targeted cancer therapies. The identified PRO instruments were studied to determine which HRQoL issues relevant to dAEs were addressed, as well as the process of development and validation of these instruments.ResultsThirteen articles identifying six PRO instruments met the inclusion criteria. Four instruments were general dermatology (Skindex-16©, Skindex-29©, Dermatology Life Quality Index (DLQI), and DIELH-24) and two were symptom-specific (functional assessment of cancer therapy-epidermal growth factor receptor inhibitor-18 (FACT-EGFRI-18) and hand-foot syndrome 14 (HFS-14)).ConclusionsWhile there are several PRO instruments that have been tested in the context of targeted cancer therapy, additional work is needed to develop new instruments and to further validate the instruments identified in this study in patients receiving targeted therapies.

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.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).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.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.

BackgroundPreliminary 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.MethodsThis 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.ResultsA total of 51 chemotherapy-receiving ESBC patients (mean age: 52.6 ± 9.5years) 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: 5423.0pg/ml; T2: 5313.6pg/ml; T3: 4050.3pg/ml; p

Since few studies have investigated whether the Distress Thermometer (DT) in Asian adolescent and young adult (AYA) cancer patients (between 15 and 39 years), we investigated the appropriateness of the DT as a screening tool for psychological symptom burden in these AYA patients and to evaluate AYA patients’ distress across a trajectory of three time points longitudinally over a 6-month period. This was a prospective, longitudinal study. Recruited Asian AYA patients were diagnosed with lymphomas, sarcomas, primary brain malignancies, or germ cell tumors. Patients completed the DT, PedsQL Generic Core Scales, and the Rotterdam Symptom Checklist. Data were analyzed using STATA version 15. Approximately half of the patients experienced clinically significant DT distress (distress score ≥ 4) early in their cancer journey with 43.1% patients presenting with distress at time of diagnosis and 47.7% patients 1 month after diagnosis. Among AYA patients > 24 years old, worry (68.3%), insurance/financial issues (61%), treatment decisions (43.9%), work/school issues (41.5%), nervousness (41.5%), and sadness (41.5%) were the top five identified problems. On the other hand, the top five identified problems among AYA ≤ 24 years were worry (54.2%), nervousness (41.7%), bathing/dressing problems (37.5%), work/school issues (33.3%), and fatigue (33.3%). DT scores were significantly associated with certain psychological symptom burden items such as worry (p

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. 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. 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

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. 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. 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. 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.

Background Breast cancer is the third leading cause of death from cancer among females in Macao, but little is known about local practice of breast cancer screening. The study aims to evaluate breast cancer screening behaviors and to identify the predictors of insufficient knowledge and attitudes towards breast cancer and its screening among female residents. Methods This was a cross-sectional study conducted from April to June 2016 in Macao. Quota sampling of women completed the modified Chinese Breast Cancer Screening Beliefs questionnaire (CBCSB) to assess their breast cancer-related perceptions, screening attitudes and behaviors. Univariate and multivariate logistic regressions were performed to identify the predictors of poor-screening practices, attitudes, knowledge and perceived barriers to mammography. Result A total of 417 women (mean age±SD: 50.5±5.7) completed surveys, with 160 (38.4%), 196 (47.0%) and 103 (24.7%) women received breast self-examination, clinical breast examination and mammography as recommended, respectively. Nulliparity (OR=2.56, 95% CI = 1.14-5.73) and low education (OR = 1.72, 95% CI = 1.04-2.84) were significantly associated with negative attitude towards health check-ups. Women did not know anyone with breast cancer (OR = 2.30, 95% CI = 1.50-3.55) were more likely to have insufficient knowledge about breast cancer. Low education (OR = 1.95, 95% CI = 1.25-3.04) and not knowing anyone with breast cancer (OR = 2.02, 95% CI = 1.31-3.13) were identified as predictors for perceived barriers to mammography. Conclusion Recommendations for breast cancer screening are poorly followed by the residents in Macao, and a culturally tailored educational program is urgently needed to raise the public's awareness of the disease and the screening practices.

Clinical prediction models promise a future of precision drug therapy. However, very few models are used in practice. Although models can eliminate unwanted clinical guesswork, several barriers hinder model implementation in practice. Here we discuss the less well-recognized barriers hindering model implementation for precision prescribing, highlighting areas that warrant attention, primarily relating to ethical and regulatory considerations that are requisite in paving the way towards a future of precision pharmacotherapy.

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.

Febrile neutropenia (FN) is a common and serious complication among cancer patients undergoing myelosuppressive chemotherapy. FN should be treated as a medical emergency because it can lead to life-threatening complications if appropriate treatment is not initiated immediately. This study provides a critical review on the current management of FN and identifies possible directions to optimize FN management.

Background Stratifying patients according to 15-day readmission risk would be useful in identifying those who may benefit from targeted interventions during and/or following hospital discharge that are designed to reduce the likelihood of readmission. Methods A prediction model was derived via a case-control analysis of patients discharged from a tertiary hospital in Singapore using multivariate logistic regression. The model was validated in two independent external cohorts separated temporally and geographically. Model discrimination was assessed using the C-statistic while calibration was assessed using the Hosmer-Lemeshow χ2 and the Brier score statistics. Results A total of 1291 patients were included with 670, 101, and 520 patients in the derivation, temporal, and geographical validation cohorts, respectively. Age (OR: 1.02, 95% CI: 1.01 – 1.03, p = 0.008), anemia (OR: 2.08, 95% CI: 1.15 – 8.05, p = 0.015), malignancy (OR: 3.37, 95% CI: 1.16 – 9.80, p = 0.026), peptic ulcer disease (OR: 3.05, 95% CI: 1.12 – 8.26, p = 0.029), chronic obstructive pulmonary disease (OR: 3.16, 95% CI: 1.24 – 8.05, p = 0.016), number of discharge medications (OR: 1.06, 95% CI: 1.01 – 1.12, p = 0.026), discharge to nursing homes (OR: 3.57, 95% CI: 1.57 – 8.34, p = 0.003), and premature discharge against medical advice (OR: 5.05, 95% C.I: 1.20 – 21.23, p = 0.027) were independent predictors of 15-day readmission risk. The model demonstrated reasonable discrimination on the temporal and geographical validation cohorts with C-statistic of 0.65 and 0.64, respectively. Model miscalibration was observed in both validation cohorts. Conclusion A 15-day readmission risk prediction model is proposed and externally validated. The model facilitates the targeting of interventions for patients who are at high risk of an early readmission. This article is protected by copyright. All rights reserved.

Limited data are available on how symptom burden affects health-related quality of life (HRQoL) in patients with sarcoma. This study aims to describe the symptom burden, HRQoL, and medication use in adult sarcoma patients. A single-center, cross-sectional study was conducted, and 79 patients were evaluated using three tools: the Rotterdam Symptom Checklist (RSCL), the Beck Anxiety Inventory (BAI), and the Functional Assessment of Cancer Therapy scale—General (FACT-G). Patients’ demographic and clinical information, medication history, and use of concomitant medications were recorded. The proportion of patients with clinically significant RSCL score for a particular symptom was compared with the percentage of patients receiving medication for that symptom. The mean age was 57.3 ± 15.2 years, with majority of the patients diagnosed with stromal tumor (46.8 %), leiomyosarcoma (15.2 %), and liposarcoma (10.1 %). The most prevalent physical symptoms experienced were tiredness (2.38 ± 1.00), lack of energy (2.04 ± 1.02), and difficulty sleeping (2.00 ± 1.15). The most common psychological symptoms experienced were irritability (1.92 ± 1.01), worrying (1.86 ± 0.90), and anxiety (1.68 ± 0.74). Few (6.3 %) patients received hypnotics while 33.0 % of patients reported difficulty sleeping. A proportion of patients (27.9 %) reported experiencing lack of appetite with only 1.3 % received appetite stimulants. Adult sarcoma patients experience significant physiological and psychological symptom burden, which has a strong negative impact on HRQoL, with a number of physiological symptoms undertreated with pharmacotherapy.

Some patients experience nausea and/or vomiting (NV) before receipt of chemotherapy. Our objective was to evaluate the impact of prior chemotherapy-induced NV (CINV) on the incidence of anticipatory NV in later cycles.This multicenter, prospective non-interventional study enrolled chemotherapy-naïve adults scheduled to receive highly or moderately emetogenic chemotherapy (HEC/MEC) for cancer in six Asia Pacific countries, excluding those with emesis within 24 h before cycle 1 chemotherapy. On day 1 before chemotherapy, patients answered four questions regarding emesis in the past 24 h, nausea, expectation of post-chemotherapy nausea, and anxiety in the past 24 h, the latter three scored from 0-10 (none-maximum). Multivariate logistic regression was used to assess the impact of prior CINV on anticipatory NV in cycles 2 and 3.Five hundred ninety-eight patients (59% female) were evaluable in cycle 2 (49% HEC, 51% MEC). The incidence of anticipatory emesis was low before cycles 2 and 3 (1.5-2.3%). The incidence of clinically significant anticipatory nausea (score of ≥3) was 4.8, 7.9, and 8.3% before cycles 1, 2, and 3, respectively, with adjusted odds ratio (OR), 3.95 (95% confidence interval (CI), 2.23-7.00; p 0.001) for patients with clinically significant nausea in prior cycles, compared with none. The adjusted ORs for other anticipatory NV endpoints ranged from 4.54-4.74 for patients with prior CINV. The occurrence of clinically significant anxiety in the prior cycle also resulted in a significantly increased likelihood of anticipatory nausea.These findings highlight the importance of preventing CINV in cycle 1 to reduce anticipatory NV in subsequent cycles.

Preventing and managing chemotherapy-induced nausea and vomiting (CINV) remain important goals. The objective of the Pan Australasian chemotherapy-induced emesis burden of illness (PrACTICE) study was to describe the incidence of CINV after highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer in current clinical practice in Australia and five Asian countries (China, India, Singapore, South Korea, and Taiwan). This prospective, observational study of CINV was conducted at 31 sites in these six countries from August 2011 through September 2012 and enrolled male and female adult patients (≥18 years of age) naive to HEC and MEC who were scheduled to receive at least two cycles of single-day chemotherapy. The primary effectiveness endpoint was complete response, defined as no vomiting or use of rescue therapy, during chemotherapy cycle 1 in the overall phase (0–120 h), acute phase (0–24 h), and delayed phase (>24–120 h). Study outcomes were analyzed descriptively. Primary outcomes, CINV incidence, and treatment patterns (chemotherapy, CINV prophylaxis, rescue medication prescription, and rescue medication use) were assessed by phase (overall, acute, delayed), by cycle (as appropriate), within and across countries, and by level of chemotherapy emetogenicity (HEC vs MEC). The impact of CINV in cycle 1 on CINV in cycle 2 was analyzed for all patients with evaluable data for cycle 2. No site-specific analyses were performed. The remainder of this special series of papers reports on the results of this study.

Background The purpose of this study was to analyze the trajectory of and risk factors for chemotherapy-induced nausea and vomiting in Asian patients with head and neck cancer. Methods Adult patients with head and neck cancer scheduled to receive cisplatin-based chemotherapy were recruited for the study. Clinical events were collated from standardized diaries. Results Two hundred thirty-five patients were included in the analyses. The majority (75.7%) was men, Chinese (81.7%), and manifested nasopharyngeal cancer (83.4%). The overall incidence of significant nausea and vomiting was 73.7% and 24.7%, respectively, with single-day cisplatin regimens of 48.9% and 28.9%, respectively, with the multiple-day cisplatin regimen. Patients using complementary alternative medicine were less likely than others to achieve a complete response to antiemetics. Conclusion Although postchemotherapy vomiting is relatively well controlled in Asian patients with head and neck cancer, postchemotherapy nausea remains problematic in this population. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1349–1357, 2015

To identify the technological preferences of aging cancer patients with regard to the delivery services and devices for preventing/solving three common drug-related problems (DRPs): medication nonadherence, lack of knowledge in medications, and side effects management. A survey was conducted at a cancer center from May to August 2011. Delivery services included in the interviewer-administered questionnaire included voice-activated dispensing, voice reminders, electronic messages, helplines, and mobile phone applications, among others. Three devices were proposed—watches, bracelets, and mobile phones. Descriptive statistics and chi-square tests were performed. A total of 361 surveys were analyzed. Median age of respondents was 61 years. The majority of respondents were female (57.3 %), Chinese (88.9 %), and 65 years and younger (73.4 %). More than half (59.0–63.2 %) were receptive to the use of the delivery services. Patients preferred voice reminder alerts (28.0 %) and electronic messages (17.7 %) to help with their medication nonadherence, and helplines for medications (52.6 %) and side effects management (47.4 %). Higher educated patients were more likely to want delivery services to improve their medication adherence (p = 0.045) and knowledge in medications management (p = 0.050). Middle age patients (age 50–65) were also more likely to want delivery services for the latter DRP (p = 0.009). Among those who wanted delivery services, most preferred mobile phones. Middle age and elderly cancer patients are accepting of delivery services to help them with their DRPs. With middle aged patients being more receptive of the delivery services, technology can potentially play an important role in minimizing DRPs.

The American College of Clinical Pharmacy 2013 Educational Affairs Committee was charged with developing recommendations for the minimum qualifications required for clinical pharmacy practice faculty in United States colleges and schools of pharmacy with respect to education, postgraduate training, board certification, and other experiences. From a review of the literature, the committee recommends that clinical pharmacy practice faculty possess the following minimum qualifications, noting that, for some positions, additional qualifications may be necessary. Clinical pharmacy practice faculty should possess the Doctor of Pharmacy degree from an Accreditation Council for Pharmacy Education–accredited institution. In addition, faculty should have completed a postgraduate year one (PGY1) residency or possess at least 3 years of direct patient care experience. Faculty who practice in identified areas of pharmacotherapy specialization, as identified by American Society of Health-System Pharmacists postgraduate year two (PGY2) residency guidelines, should have completed a PGY2 residency in that area of specialty practice. Alternatively, faculty should have completed a minimum of a PGY1 residency and 1 additional year of practice, with at least 50% of time spent in their area of specialization, which is documented in a portfolio, or 4 years of direct patient care in their area of specialization, which is documented in a portfolio. Fellowship training or a graduate degree (e.g., Ph.D.) should be required for research-intensive clinical faculty positions. All faculty should obtain structured teaching experience during or after postgraduate training, preferably through a formal teaching certificate program or through activities documented in a teaching portfolio. A baseline record of scholarship should be obtained before hire as clinical pharmacy practice faculty through exposure in postgraduate programs or previous employment. Faculty should be board certified before hire or attain board certification within 2 years of hire through the Board of Pharmacy Specialties (BPS) or, if appropriate for the practice area, through a nonBPS-certifying agency. If no certification exists in the area of specialty, the faculty member should develop a portfolio with evidence of excellence in clinical practice, teaching, and scholarship.

Dear Editor, With scientific advances in cancer supportive care and the incorporation of effective supportive care strategies into contemporary cancer treatment, there has been a substantial reduction in the occurrence of severe toxicities traditionally associated with cytotoxic chemotherapy over the past two decades. For example, appropriate prophylaxis with antiemetics (including a 5-HT3 antagonist, corticosteroid, and NK-1 antagonist) has greatly reduced chemotherapy-induced nausea and vomiting, colony-stimulating factors have curbed febrile neutropenia, and the integrated use of mouth care and palifermin has decreased the severity of oral mucositis. In addition, the introduction of structured management and care pathways into clinical practice has widely promoted these supportive care strategies for patients. We may not currently have all the answers on the prevention of chemotherapyinduced toxicities, but most oncology clinicians today can capably handle toxicities which were previously considered difficult to manage. Innovations in cancer therapeutics have improved the oncologist’s toolkit to cure and control many cancers previously difficult to manage. Targeted therapy agents are now commonly used in the management of cancers ranging from chronic myeloid leukemia to renal cell carcinoma, and new indications and increased lines of therapy continue to arise. Initially “targeted” drugs were thought to have unique mechanisms for targeting cancer cells and were considered to produce fewer side effects than traditional cytotoxic chemotherapy. Importantly, however, clinicians are now observing a number of emerging and highly prevalent side effects associated with the use of targeted therapies [1]. These agents, which carry with them significant financial cost, are also associated with an increase in chronic complications that can decrease a patient’s quality of life [2]. We must, therefore, strive to understand and be responsive to the side effects of these novel therapeutics to enable optimal patient adherence to and participation in their treatment. In this commentary, we highlight toxicities that are commonly associated with targeted therapies, namely dermatological, gastrointestinal (diarrhea and stomatitis), hepatotoxicity, cardiotoxicity, neurotoxicity, and immunotoxicity. More importantly, we will emphasize the current impediments to understanding the mechanisms behind emerging side effects and the lack of effective strategies for managing these toxicities.

Background Most previous studies of the incidence and economic impact of drug-related hospital admissions were not cancer specific, despite the fact that drug-related problems (DRPs) are of particular concern in oncology. Objective The goals of this study were to assess the economic impact, particularly the length of stay (LOS) and direct medical costs (DMC), of drug-related hospital admissions and the associated factors in cancer patients in Singapore. Methods A prospective study was conducted over a 5-month period in 2 oncology wards at the largest acute tertiary hospital in Singapore. Drug-related admissions were identified from all oncology admissions to these wards, and the demographic, clinical, and cost data of these drug-related admissions were collected. The association between LOS and DMC as well as their associations with age, severity, and preventability of DRPs were examined. A nationwide estimation was made to determine the overall DMC of drug-related hospital admissions among cancer patients. Results A total of 151 drug-related admissions that occurred among 137 cancer patients were identified. The mean DMC (in Singapore dollars [SGD]) and LOS per drug-related admission were SGD $4747 and 6.1 days, respectively. A nationwide extrapolation estimated an annual total DMC of SGD $16.2 million. Longer LOS was found to be correlated with higher DMC ( r s = 0.86, P P = 0.02). Conclusions Drug-related hospitalization among cancer patients is costly; therefore, more attention is warranted to develop and improve strategies for preventing drug-related morbidity and mortality in cancer patients.

Studies have examined drug-related problems (DRPs) that have led to hospital admissions in the general population. However, there is a lack of information on the characteristics of DRPs in the cancer population. The objective of this study was to investigate the type, causality, severity, and preventability of DRPs that result in unplanned hospitalizations among cancer patients. This was a prospective, cohort study conducted in two oncology wards between July and December 2012. All patients who were diagnosed with solid tumor or lymphoma and required unplanned hospitalization were included. The incidence of DRPs among hospital admissions was captured, and the nature of the DRPs (causality, severity, and preventability) was characterized. There were 1,299 admissions and 1,275 were eligible for analysis. Among the 1,275 eligible admissions, 158 (12.4 %) were considered to be associated with a DRP. In the 158 admissions associated with DRPs, 164 DRPs were found. The majority of the DRP-related admissions were adverse drug reactions (ADRs) (n = 155/164, 94.5 %), probable (n = 98, 59.8 %), moderately severe (n = 155, 94.5 %), and probably or definitely preventable (n = 86, 52.4 %). Most patients with DRPs recovered and were discharged. Febrile neutropenia was the most common adverse drug reaction, and drug combinations involving antihypertensives and long-term corticosteroids raised the risks for potential drug-drug interactions among patients with cancer. The incidence of DRP-induced unplanned hospital admissions was 12.4 % among cancer patients. Approximately half of these were preventable events.

Background Cancer survivors have been reported to face challenges as they return to work after completing antineoplastic treatment. In order to understand the burden of return-to-work challenges among cancer survivors in Singapore, we aim to describe the work-related outcomes, including employment rates, absenteeism and presenteeism, among local cancer survivors. Methods This was a cross-sectional study conducted at the National Cancer Centre Singapore in 2018. Breast cancer, colorectal cancer and lymphoma survivors who were in disease remission and have completed treatment for at least 6 months were recruited. Employment history and absenteeism data in the past 6 months were collected using self-administered questionnaires. Presenteeism was self-reported using the Work Limitations Questionnaire. Results A total of 501 patients were recruited. Most participants were Chinese (79.6%), followed by Malay (11.8%), Indian (4.6%) and other ethnicities (4.0%). Over half were breast cancer survivors (69.5%), followed by colorectal cancer (15.5%) and lymphoma (15.0%) survivors. The median age of the participants was 55.7 years (IQR: 50.1 to 60.5 years) while the median time after primary treatment completion was 3.7 years (IQR: 1.9 to 6.1 years). The majority of cancer survivors were employed with most participants reporting working full-time (47.5%), followed by part-time workers (10.2%) and self-employed individuals (5.8%). Out of the survivors who did not have paid employment, a substantial proportion (24.3%) were unemployed due to health-related reasons. Among employed participants, 56.9% reported taking time off work due to ill health or to see a physician in the past 6 months. The median absenteeism rate reported among working survivors was 0.8% of working time (range: 0 to 73.1%) while the median presenteeism or productivity loss at work due to health-related problems was reported to be 1.2% (range: 0 to 20.3%). Conclusions A significant proportion of cancer survivors in Singapore require time off from work or leave employment due to health-related issues. Further studies should be conducted to identify survivors who are at high risk for return-to-work challenges and should be offered occupational rehabilitation. Legal entity responsible for the study The authors. Funding Singapore Cancer Society. Disclosure All authors have declared no conflicts of interest.

Background Breast cancer survivors (BCS) often experience cancer-related fatigue (CRF), a distressing condition which does not have an effective standardised pharmacological intervention. Xiang Bei Yangrong Tang (XBYRT), a modified herbal traditional Chinese medicine (TCM) decoction, is formulated for the management of CRF in BCS. In this in vitro study, we evaluated the herb-enzyme inhibition for 9 of the herbal TCMs from the XBYRT formulation, on CYP2D6 activity. Methods The XBYRT herbal components evaluated were Radix Astragaliseu Hedysari, Radix Codonopsis Pilosulae, Rhizoma Atractylodis Macrocephalae, Poria cocos, Radix Paeoniae Alba, Fructus Ligustri Lucidi, Rhizoma Cyperi, Radix Polygalae and Bulbus Fritillariae Thunbergii. Varying concentrations of the herbal TCMs were assayed for herb-enzyme inhibition using the Vivid P450 CYP2D6 assay kit. The percentage inhibition for the maximum XBYRT concentration and the half maximal inhibitory concentrations (IC50) were determined. The maximum XBYRT concentration was calculated based on the total dosage of herbal components consumed, without accounting for first pass metabolism. The IC50 was calculated using the non-linear regression from GraphPad Prism 5. Results Assayed at the maximum XBYRT concentration, herbal components exhibiting the highest inhibition levels were Radix Codonopsis Pilosulae (56.8%), Poris cocos (45.0%), Fructus Ligustri Lucidi (42.9%) and Radix Paeoniae Alba (35.5%). The IC50 values of these four herbal components were 481µg/ml, 572 µg/ml, 447 µg/ml and 475 µg/ml respectively. The other 5 herbal components exhibited Conclusions Components of XBYRT display potential CYP2D6 enzymatic inhibition activities. Hence, caution should be taken with the concomitant usage of XBYRT with drugs that are CYP2D6 substrates such as tamoxifen. In vivo and clinical studies are required to ascertain the actual effects of these herbal components on drug metabolism. Legal entity responsible for the study The authors. Funding Ministry of Health Singapore. Disclosure All authors have declared no conflicts of interest.

The use of granulocyte colony-stimulating factor (G-CSF) as a prophylaxis against febrile neutropenia (FN) is well documented in the literature; however, the therapeutic use of G-CSF in the treatment of FN remains controversial. This study assessed the efficacy of adjunctive G-CSF in the treatment of FN by evaluating clinical outcomes.This was a single-center, prospective cohort study conducted at the National Cancer Center in Singapore. Adult patients who had received chemotherapy and developed FN between January 2009 and January 2012 were included in the analysis. The clinical efficacy of adjunctive G-CSF was evaluated by investigating the duration of hospitalization, duration to absolute neutrophil count (ANC) recovery, duration of grade IV neutropenia, duration to fever resolution, duration of antibiotic therapy, and incidence of documented infections. A multivariate analysis was performed to identify patients who could potentially benefit from adjunctive G-CSF.Four hundred and thirty patients were analyzed. Majority manifested low-risk FN (81.2%) based on the Multinational Association of Supportive Care in Cancer (MASCC) scoring. Compared to patients who did not receive adjunctive G-CSF, patients receiving adjunctive G-CSF had a nonsignificant reduction in the duration of hospitalization (3.5 vs. 3.7 days, p = 0.41) and in ANC recovery time (3.4 vs. 3.5 days, p = 0.76). Neutropenia-related mortality was lower among those who have received adjunctive G-CSF (2.4 vs. 8.4%, p = 0.006). Patients of Indian ethnicity and those who underwent gemcitabine-containing chemotherapy were less likely to receive adjunctive G-CSF treatment.This observational study suggested that adjunctive G-CSF may confer clinical benefits among solid tumor and lymphoma patients with established febrile neutropenia. Further research should be conducted to validate the findings.

Sunitinib commonly exhibits dose-limiting dermatological toxicities (DTs) that adversely affect health-related quality of life (HRQoL). Pharmacological activity of sunitinib is attributed to sunitinib and an equipotent, active metabolite, SU12662. The objective of this study is to compare the dermatotoxic potential of sunitinib and SU12662, and changes in HRQoL due to DTs. A prospective cohort study was conducted on metastatic renal cell carcinoma patients. Plasma drug concentrations were determined by high-performance liquid chromatography. DTs were graded by Common Terminology Criteria for Adverse Events. HRQoL of patients with hand–foot skin reaction (HFSR) was assessed by the hand–foot syndrome-specific quality-of-life questionnaire (HFS-14). In addition, the IC50s of both compounds were determined with HaCaT keratinocytes. Sunitinib was more dermatotoxic in vitro, with a lower IC50 than SU12662 (23.33 vs. 35.32 μM, p = 0.02). Similar results were observed in vivo, with higher sunitinib-to-SU12662 ratio in patients with pruritus, than patients without pruritus (p = 0.04). Higher HFS-14 scores were observed in patients with higher HFSR grade and in those with both hands and feet affected, indicating poorer HRQoL. Sunitinib may be more dermatotoxic than SU12662 from both in vivo and in vitro evidences. Therefore, appropriate management of DTs may be essential, especially in patients with a reduced sunitinib metabolising ability.

Introduction Cancer-related fatigue (CRF) has been suggested to be associated with the occurrence of chemotherapy-induced nausea and vomiting (CINV). This study aims to evaluate the potential of CRF in predicting the occurrence of CINV. Method This is a prospective, observational study. Recruited patients received moderately to highly emetogenic single-day chemotherapy regimens. On the day of chemotherapy, patients were instructed to provide a score (Likert scale of 0–10) to describe how CRF interfered with his or her ability to engage in daily activities and a score for how severe it was. Patients were then given a standardized 5-day diary to document their CINV events. Results A total of 473 eligible patients (median age: 55 years, interquartile range (IQR): 48–61 years) were recruited, with most of the patients diagnosed with gastrointestinal (45%) and breast (37%) cancers. The median score of fatigue interference was 3 (IQR: 0–5). After confounders were adjusted for, patients with low fatigue interference scores (≤3) were more likely to achieve complete protection (no nausea, no vomiting, and no breakthrough antiemetics) of CINV (adjusted odds ratio = 1.57, 95%CI [1.05, 2.35], p = 0.027). Conclusion This is the largest study to date to evaluate the association between CRF and CINV. Patients experiencing CRF possessed a higher risk of poor control for CINV. Copyright © 2013 John Wiley & Sons, Ltd.

The use of telemedicine for cancer patients is limited, particularly in Asia. These patients need to be monitored because more are being treated as outpatients, so that any treatment-related side effects can be managed. We assessed the feasibility and acceptance of a pharmacist-run tele-oncology service to monitor chemotherapy-induced nausea and vomiting (CINV) in ambulatory cancer patients.A single-center, prospective study was conducted at a local cancer center. Patients' CINV symptoms were monitored through short message service (SMS) for 5 days post-chemotherapy. Feasibility was measured by patients' adherence to the service, patient satisfaction, and number of pharmacist interventions. Acceptance was measured by the accrual rate.The accrual rate was 37.6% (68/181 patients). Sixty patients (median age, 49.5 years) completed the study. Overall adherence was 73.3%. The majority (90.0%) were comfortable with the duration of SMS monitoring, especially adherent patients (95.5% versus 75.0%, p=0.038). Over half (61.7%) found the SMS advice useful. Twenty-two intervention calls were made by pharmacists for uncontrolled CINV.A pharmacist-run tele-oncology service for real-time monitoring of CINV is feasible in ambulatory cancer patients. Incorporating the monitoring of other side effects will enhance its value and acceptance by patients for post-chemotherapy symptom management.

Psychological distress, such as anxiety, is commonly experienced by breast cancer patients. This study was designed to evaluate the presentation of anxiety symptom domains among Asian breast cancer patients and to identify clinical factors that were associated with occurrence of anxiety. An observational study was conducted between August 2009 and January 2012. Breast cancer patients (stages I to III) with different chemotherapy treatment status completed the Beck Anxiety Inventory (BAI) to evaluate the prevalence and severity of their anxiety symptoms. Demographical and clinical data were collected. Multiple linear regression was conducted to delineate clinical factors associated with anxiety. A total of 319 patients were recruited (age: 51 ± 9 years; 80.9 % Chinese; 69.6 % stage I/II). The median BAI total score was 8 (IQR, 4–14). Anxiety severities varied greatly across patients with different chemotherapy treatment status: patients who were receiving concurrent chemotherapy at the point of assessment (n = 161) experienced more severe anxiety symptoms, as compared to pre-chemotherapy receiving (n = 78) patients and post-chemotherapy (n = 88) patients (29.8 % vs. 9.0 % vs. 20 %, respectively; p = 0.021). Regression model identified fatigue (p

This study evaluated the prevalence, impact and predictive factors for the occurrence of febrile neutropenia (FN) in elderly patients receiving adjuvant myelosuppressive chemotherapy despite primary prophylaxis with G-CSF (breakthrough FN).This was a single-centre, observational, retrospective cohort study. Elderly cancer patients (≥ 65 years old) who have received adjuvant chemotherapy with primary prophylaxis using G-CSF from Jan 2008 to Aug 2011 were included. Variables identified by the univariate analysis as being associated with FN were included in a multivariable logistic model to investigate the independence of its association with FN.One hundred and forty-five patients and 704 cycles of chemotherapy were analyzed in this study, of which majority were Chinese (79.3 %). The median age of the patients was 69 years old (IQR: 66, 74). Majority of these patients were diagnosed with lymphoma (54.5 %), followed by breast cancer (34.5 %) and small cell lung cancer (8.3 %). In total, 24 patients (16.6 %) manifested at least one episode of FN, of which 41.7 % occurred during the first cycle of treatment. Only a minority of FN patients had clinically significant dose delay or reduction (25.0 % and 12.5 %, respectively). After adjustment with confounders (gender, baseline lymphocyte counts and baseline absolute neutrophil counts), patients with ≥ 2 comorbidities were at higher risk to develop breakthrough FN (AOR = 4.42, 95 %CI: 1.36-14.40, p = 0.014).Breakthrough FN is prevalent among elderly cancer patients receiving adjuvant chemotherapy despite G-CSF support, particularly among patients with more than two comorbidities.

This study aims to develop and validate a prognostic model (PROMASCC) by incorporating the Functional Assessment of Cancer Therapy-Neutropenia (FACT-N) elements, with the Multinational Association of Supportive Care in Cancer (MASCC) risk index, for identifying low-risk patients with febrile neutropenia (FN) for developing serious complications. This was a single-center, cross-sectional observational study. Either English or Chinese versions of the FACT-N were administered to the eligible patients according to their language preference within 7 days of FN onset. Univariate analyses and multivariate analyses were performed to construct the PROMASCC model. The prognostic performance was compared between the PROMASCC model and MASCC risk index. The internal validation of the PROMASCC model was examined by bootstrapping technique. From August 2014 to April 2016, a total of 120 eligible patients were included in this study. In the univariate analyses, only the malaise subscale score has been significantly associated with the favorable outcome (without complications) (P = 0.024). Compared to the MASCC risk index, the PROMASCC model has shown advantages on the improved specificity (64.3 vs. 38.1%) and positive predictive value (81.0 vs. 73.7%), lower misclassification rate (24.2 vs. 25.8%), and increased area under receiver-operating characteristic curve (0.732 vs. 0.658). The bootstrapping procedure estimates the optimism-corrected area for the PROMASCC model to be 0.731 (95% CI 0.648 to 0.814). This study has developed and validated a PROMASCC model and demonstrated that additional measurement on patient’s fatigue level could improve the risk stratification of patients with FN.

Aims Adverse drug reactions (ADRs) contribute to poorer patient outcomes and additional burden to the healthcare system. However, data on the true burden, relevant types and drugs causing ADRs are lacking. The aim of this study was to determine the prevalence of ADR-related hospitalization in the general adult population in Singapore and to investigate their characteristics. Methods We prospectively recruited 1000 adult patients with unplanned admission to a large tertiary-care hospital. Two independent reviewers evaluated all suspected ADRs for causality, type, severity and avoidability. The prevalence of ADR-related hospitalization was calculated based on ‘definite’ and ‘probable’ ADRs. Logistic regression was used to evaluate predictors for having an ADR at admission. Results The prevalence of all ADRs at admission was 12.4% (95% CI: 10.5–14.6%) and ADRs causing admission was 8.1% (95% CI: 6.5–10.0%). The most common ADRs were gastrointestinal-related. The most common drug category causing ADRs were cardiovascular drugs. Patients with ADRs had a longer length of stay than those who did not (median 4 vs. 3 days, P = 1.70 × 10−3). About 30% of ADRs at admission were caused by at least one drug with a clinical annotation in the Pharmacogenomics KnowledgeBase (PharmGKB), suggesting that some of these ADRs may have been predicted by pharmacogenetic testing. Conclusions We have quantified the burden and characteristics of clinically impactful ADRs in the Singaporean general adult population. Our results will provide vital information for efforts in reducing ADRs through targeted vigilance, patient education and pharmacogenomics in Singapore.

Purpose With the emergence of biosimilar filgrastim to the market, there is a gradual decrease in the listed price of the originator product of filgrastim over the years, and this could have an impact on the cost-effectiveness of filgrastim in the treatment of febrile neutropenia (FN). A cost-effectiveness analysis would allow clinicians to make informed decision when considering the therapeutic filgrastim among low-risk FN patients. This study aims to evaluate the cost-effectiveness of adding therapeutic filgrastim to antibiotics in the treatment of established FN among patients with solid tumors and lymphomas. Methods A decision tree model was created to compare two treatment options for established FN as follows: (1) antibiotics alone (standard care) and (2) antibiotics with therapeutic filgrastim (comparator). The target population was a hypothetical cohort of adult cancer patients with solid tumors or lymphomas hospitalized with FN in Singapore. The analysis was performed from a hospital’s perspective over a 21-day time horizon. The main outcome measures included costs, quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to evaluate the robustness of the results. Findings Compared with antibiotics alone, the treatment strategy of antibiotics with therapeutic filgrastim was a dominant choice, incurring a cost saving of US$125 per patient (comparator versus standard care: US$9110 versus US$9235) and additional health benefit of 0.0007 QALY gained per patient (comparator versus standard care: 0.0450 versus 0.0443). Model results were robust against the parameter variations in the one-way sensitivity analyses, but increasing the cost of filgrastim beyond US$87 per injection would increase the ICER to >US$50,000/QALY. Furthermore, the strategy of antibiotics with therapeutic filgrastim was the preferred choice (dominant or cost-effective) in 83.7% of the model iterations at a willingness-to-pay threshold of US$50,000/QALY. Implications From a hospital’s perspective, the therapeutic filgrastim, in conjunction with antibiotics, in the treatment of FN is cost effective. This provides evidence to support the routine use of filgrastim for the treatment of FN among adult cancer patients with solid tumors and lymphomas.

Aims To evaluate the association between HbA1c coefficient of variation (HbA1c-CV) and 3-year new-onset albuminuria risk. Methods A retrospective cohort study involving 716 normoalbuminuric type 2 diabetes patients was conducted between 2010 and 2014. HbA1c-CV was used to categorize patients into low, moderate or high variability groups. Multivariate logistic models were constructed and validated. Integrated discrimination (IDI) and net reclassification (NRI) improvement indices were used to quantify the added predictive value of HbA1c-CV. Results The mean age of our cohort was 56.1 ± 12.9 years with a baseline HbA1c of 8.3 ± 1.3%. Over 3-years of follow-up, 35.2% ( n = 252) developed albuminuria. An incremental risk of albuminuria was observed with moderate (6.68–13.43%) and high (above 13.44%) HbA1c-CV categories demonstrating adjusted odds ratios of 1.63 (1.12–2.38) and 3.80 (2.10–6.97) for 3-year new-onset albuminuria, respectively. Including HbA1c-CV for 3-year new-onset albuminuria prediction improved model discrimination (IDI: 0.023, NRI: 0.293, p Conclusion HbA1c-CV improves 3-year prediction of new-onset albuminuria. Together with mean HbA1c, baseline urine albumin-to-creatinine ratio and presence of hypertension, accurate 3-year new-onset albuminuria prediction may be possible.

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.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.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.Both English and Chinese versions of BAI are valid, reliable, and possibly equivalent for future use.

PURPOSE: This review summarizes the recommendations for the prophylaxis of nausea and vomiting in adults receiving highly emetogenic chemotherapy (HEC) which includes cisplatin, mechlorethamine, streptozocin, cyclophosphamide >1500 mg/m(2), carmustine, dacarbazine, and the combination of an anthracycline and cyclophosphamide (AC) administered to women with breast cancer, as agreed at the MASCC/ESMO Antiemetic Guidelines Update meeting in Copenhagen in June 2015.METHODS: A systematic review of the literature using PubMed and the Cochrane Database from 2009 to June 2015 was performed.RESULTS: The NK1-receptor antagonists netupitant (300 mg given in combination with palonosetron 0.5 mg as NEPA) and rolapitant have both completed phase II and III programs and were approved by FDA (both) and EMA (NEPA) in 2014-2015. Addition of one of these agents (or of (fos)aprepitant) to a combination of a serotonin (5-HT)3-receptor antagonist and dexamethasone improved the number of patients with a complete response (no emesis and no rescue medication) days 1-5 after AC HEC with 8-9 % and after non-AC HEC by 8-20 %. Olanzapine has improved control of delayed nausea as compared to aprepitant in a randomized open designed study. In the prophylaxis of delayed nausea and vomiting, metoclopramide is an option instead of aprepitant in patients receiving cisplatin-based chemotherapy and dexamethasone is an option instead of aprepitant in patients receiving AC chemotherapy.CONCLUSIONS: Two new NK1-receptor antagonists (netupitant and rolapitant) have been included in the updated recommendations as additional options to aprepitant or fosaprepitant. Addition of one of these NK1-receptor antagonists to a combination of a 5-HT3-receptor antagonist and dexamethasone is recommended in both non-AC HEC and AC HEC. Olanzapine is included as an option in HEC in particular if nausea is the main symptom.

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.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-β 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.This review has identified that cytokines are differentially linked with CRF according to the various types of chemotherapy regimens.

Background Oncology pharmacists are capable of providing medication therapy management (MTM) because of their level of training, practice experiences, and responsibilities. Very little data exist about their current practice, including changing roles in the multidisciplinary team, overall impact, and effects in the education of patients and healthcare professionals. Methods A 70-item survey about oncology pharmacists' activities in oral chemotherapy programs, MTM, and collaborative practice agreements (CPAs) was deployed using a web survey tool (Qualtrics, Provo, UT, USA), targeting pharmacist members of American College of Clinical Pharmacy (ACCP) Hematology/Oncology Practice and Research Network (PRN). The objective of this study was to determine oncology pharmacists' activities in areas of oral chemotherapy programs, MTM, and CPAs. A cross-sectional survey was distributed to the ACCP Hematology/Oncology PRN membership. Investigational Review Board approval was obtained. Results Of the 795 members who were sent the survey, 81 members (10%) responded; 33 respondents (47%) are involved with an oral chemotherapy program; with 42% measuring outcomes of programs. Only six pharmacists (19%) have published or presented their data. A total of 28 (35%) respondents provide MTM services, with almost half (43%) of these MTM services being dictated by CPAs. A small fraction of these pharmacists (21.4%) reported conducting quality assurance evaluations of their MTM services and three pharmacists (10.7%) reported publishing their results. Those pharmacists practicing under CPAs ( n = 28) were surveyed as to activities included in their CPA. The most common activities included adjusting medication, ordering, interpreting, and monitoring lab tests, developing therapeutic plans and educating patients. Reimbursement for providing these services was uncommon: MTM (4%), oral chemotherapy program (6%), and CPA services (11%). Reported obstacles to reimbursement included lack of understanding, administrative assistance, or time with setting up reimbursement models within the institution. Conclusion Many oncology pharmacists are participating in oral chemotherapy programs, MTM, and/or CPAs and perceived barriers were identified. Increased efforts should be directed toward prospectively reporting and assessing the impact these services have on patient care.

Chemotherapy-induced nausea and vomiting (CINV) is presented in over 30% of cancer patients receiving highly/moderately emetogenic chemotherapy (HEC/MEC). The currently recommended antiemetic therapy is merely based on the emetogenic level of chemotherapy, regardless of patient's individual risk factors. It is, therefore, critical to develop an approach for personalized management of CINV in the era of precision medicine. A number of variables were involved in the development of CINV. In the present study, we pooled the data from 2 multi-institutional investigations of CINV due to HEC/MEC treatment in Asian countries. Demographic and clinical variables of 881 patients were prospectively collected as defined previously, and 862 of them had full documentation of variables of interest. The data of 548 patients from Chinese institutions were used to identify variables associated with CINV using multivariate logistic regression model, and then construct a personalized prediction model of nomogram; while the remaining 314 patients out of China (Singapore, South Korea, and Taiwan) entered the external validation set. C-index was used to measure the discrimination ability of the model. The predictors in the final model included sex, age, alcohol consumption, history of vomiting pregnancy, history of motion sickness, body surface area, emetogenicity of chemotherapy, and antiemetic regimens. The C-index was 0.67 (95% CI, 0.62–0.72) for the training set and 0.65 (95% CI, 0.58–0.72) for the validation set. The C-index was higher than that of any single predictor, including the emetogenic level of chemotherapy according to current antiemetic guidelines. Calibration curves showed good agreement between prediction and actual occurrence of CINV. This easy-to-use prediction model was based on chemotherapeutic regimens as well as patient's individual risk factors. The prediction accuracy of CINV occurrence in this nomogram was well validated by an independent data set. It could facilitate the assessment of individual risk, and thus improve the personalized management of CINV.

Author(s): Chae, Jung-Woo; Ng, Terence; Yeo, Hui Ling; Shwe, Maung; Gan, Yan Xiang; Ho, Han Kiat; Chan, Alexandre | Abstract: ObjectiveExpression 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 GgC) and TNF-308 (rs1800629 GgA), 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.MethodsAsian 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.ResultsA 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 (pl0.001) 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.ConclusionPresent 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.

Background Scant information exists about the epidemiological characteristics and outcome of patients in the intensive care unit (ICU) at risk of acute respiratory distress syndrome (ARDS) and how ventilation is managed in these individuals. We aimed to establish the epidemiological characteristics of patients at risk of ARDS, describe ventilation management in this population, and assess outcomes compared with people at no risk of ARDS. Methods PRoVENT (PRactice of VENTilation in critically ill patients without ARDS at onset of ventilation) is an international, multicentre, prospective study undertaken at 119 ICUs in 16 countries worldwide. All patients aged 18 years or older who were receiving mechanical ventilation in participating ICUs during a 1-week period between January, 2014, and January, 2015, were enrolled into the study. The Lung Injury Prediction Score (LIPS) was used to stratify risk of ARDS, with a score of 4 or higher defining those at risk of ARDS. The primary outcome was the proportion of patients at risk of ARDS. Secondary outcomes included ventilatory management (including tidal volume [VT] expressed as mL/kg predicted bodyweight [PBW], and positive end-expiratory pressure [PEEP] expressed as cm H2O), development of pulmonary complications, and clinical outcomes. The PRoVENT study is registered at ClinicalTrials.gov, NCT01868321. The study has been completed. Findings Of 3023 patients screened for the study, 935 individuals fulfilled the inclusion criteria. Of these critically ill patients, 282 were at risk of ARDS (30%, 95% CI 27–33), representing 0·14 cases per ICU bed over a 1-week period. VTwas similar for patients at risk and not at risk of ARDS (median 7·6 mL/kg PBW [IQR 6·7–9·1] vs 7·9 mL/kg PBW [6·8–9·1]; p=0·346). PEEP was higher in patients at risk of ARDS compared with those not at risk (median 6·0 cm H2O [IQR 5·0–8·0] vs 5·0 cm H2O [5·0–7·0]; p

Purpose: Febrile neutropenia is a serious complication among cancer patients receiving myelosuppressive chemotherapy. Patient-specific risk factors, chemotherapy-related and disease-related characteristics can affect the clinical outcome and management of febrile neutropenia. Although many factors have been identified, they vary among different patient populations. We identified clinically-relevant febrile neutropenia predictors in Asian cancer patients through visualization of these factors. Methods: A single-centered, retrospective study was conducted from May to July 2011 at a local cancer center. Demographics and risk factor data were collated from electronic health records and four cancer registries. Data were summarized using descriptive statistics. Additionally, potential febrile neutropenia predictors were identified using categorical principal component and multiple correspondence analyses. Results: A total of 583 patients were analyzed. Majority was females (79%), Chinese (75%) and diagnosed with breast cancers (60%). Six risk factors were identified as potential predictors: types of cancer (16.9–19.8% of variance), chemotherapy regimen (anthracycline-based 11.8–12.9%, taxane-based 8.1%), liver function tests (alanine transaminase 8.6%, alkaline phosphatase 4.0%), renal function tests (serum creatinine 3.1%), prior granulocyte colony stimulating factor use (5.6%) and diabetes mellitus (6.6–6.9%). In terms of cancer types, lymphomas were more predictive than breast cancers. Conclusion: From our knowledge, this is the first study that has identified clinically-relevant febrile neutropenia predictors in Asian cancer patients through visualization of their risk factors. The use of these predictors to identify patients at risk for adverse reactions, such as FN, can allow clinicians to optimize prophylactic granulocyte colony stimulating factor usage in these patients.

Background There has been a recent increase in the availability and use of oral anticancer agents (OAAs). Drug–drug interactions (DDIs) involving OAAs pose a major concern in oncology practice due to these drugs' narrow therapeutic indices and potential for compromised efficacy and fatal adverse events. Objective To assess the prevalence of the coprescription of potentially interacting drug combinations involving OAAs in Singapore. Methods A retrospective review of physicians' electronic prescription records between the years 2007 and 2009 was performed in the largest cancer center in Singapore. An overall prevalence rate of potential DDIs and a prevalence rate for each individual DDI pair were calculated. Logistic regression was used to identify risk factors for potential DDIs. Results Fifty-eight clinically significant DDIs were selected for evaluation from Drug Interaction Facts and Micromedex DrugDex. A total of 39,772 OAA prescriptions prescribed to 8837 patients were reviewed. Potential DDI coprescription was found in 5.4% of the patients on OAAs and in 4.7% of the OAA prescriptions. The drug pair prescribed to the largest number of patients was prednisolone and aspirin. About half (53.3%) of the observed DDIs were found on the same prescription. On multivariate analysis, older patients, males, and those taking prednisolone had a higher risk for potential DDIs. Conclusion Although limited by the data available, the analysis of prescription records found that ∼5% of patients taking OAAs in Singapore were exposed to ≥1 potentially interacting drug combination.

Post-chemotherapy cognitive impairment has been an issue of concern in cancer survivors. While most reviews are focused on patient-related factors, it is proposed that drug-related factors may also be determinants. The objective of this review is to study the relationship between the types and dose intensities of chemotherapy regimens on cognitive impairment in breast cancer patients through a systematic literature search. Eighteen prospective studies were selected. The types, dose intensities and durations of chemotherapy regimens received by subjects were compared against prevalence results obtained in individual studies. It was observed that the duration of impairment varied across different generations of chemotherapy regimens. Concurrent administration of multiple cytotoxic agents can lead to a synergistic decline on cognition. Current clinical evidence is insufficient to evaluate the relationship between the types, dose intensities of chemotherapy regimens and cognitive impairment. More investigation is needed to examine the role of pharmacological factors in chemotherapy-associated cognitive changes.