Use of Novel National Data Sets to Monitor Chemotherapy Use and Outcomes: A Retrospective Cohort Study of Non-Small-Cell Lung Cancer in Aotearoa New Zealand.

PURPOSE: Te Aho o Te Kahu, the New Zealand Cancer Control Agency, is establishing a systemic anticancer therapy (SACT) database (Anti-Cancer Therapy-Nationally Organized Workstream [ACT-NOW]) which can be linked to other national health data collections. In this article, we explore the application of ACT-NOW data in the monitoring of uptake and outcomes after the public funding of pemetrexed in Aotearoa New Zealand. METHODS: We used the ACT-NOW collection to identify patients with advanced nonsquamous non-small-cell lung cancer, who were treated with first-line platinum-based doublet chemotherapy over an 8-year period. Data were extracted for a period of 4 years before and 4 years after the national funding of pemetrexed (November 1, 2017). Treatments were classified as historical platinum doublet (cisplatin or carboplatin with gemcitabine, vinorelbine, paclitaxel, or docetaxel) or platinum pemetrexed doublet (cisplatin or carboplatin with pemetrexed). The primary outcome was the proportion of patients receiving each treatment type, before and after November 1, 2017. To prototype linkage to outcomes data, we evaluated hospitalization and 1-year overall survival (OS) rates by treatment. RESULTS: A total of 331 patients were included from four cancer centers. All patients (116 of 116) who were treated with first-line platinum-based doublet chemotherapy between November 2013 and November 2017 received historical platinum doublet chemotherapy. After the introduction of pemetrexed, between November 2017 and November 2021, 94% (203 of 215) were treated with platinum pemetrexed doublet chemotherapy and 6% (12 of 215) with historical platinum doublet chemotherapy. Linkage to outcomes data for 1-year OS, hospitalization rates, and lengths of stay outcome data were achievable. CONCLUSION: The ACT-NOW data set has the potential to facilitate evaluation of the impact of national-level SACT funding decisions on prescribing practice and specific patient outcomes. Our results support the use of these data to inform resource planning and quality improvement.

Defining the cut-off point of clinically significant postoperative fatigue in three common fatigue scales.

PURPOSE: Postoperative fatigue (POF) is an often underestimated problem after surgery. Studies on POF often report fatigue scores without relating this to the clinical relevance for the patients. The aim of this study was to define the cut-off point for clinically significant POF in three commonly applied fatigue scales; the Postoperative Fatigue Scale, Christensen's Fatigue Scale, and the Chalder Fatigue Questionnaire. The identification of cut-off points will make it possible to indicate whether statistically significant findings of increased fatigue are of clinical relevance. METHODS: We combined data from day 0 (pre-operatively) and day 1, 3, 6, and 30 after surgery in two fatigue-related studies with 442 patients. In order to define clinically significant fatigue, a key question was added in each questionnaire; "Given your current description of fatigue, would you say it has been of considerable significance to you?"; "Yes/No". We analysed each scale's ability to identify clinically significant fatigue, by performing receiver-operating characteristics (ROC) analyses, and calculated the optimal cut-off point between Sensitivity and Specificity. RESULTS: The average weighted cut-off point for clinically significant POF when measured with the Postoperative Fatigue Scale was ≥ 50 (scale range 0-100), with Christensen's Fatigue Scale ≥ 6 (scale range 1-10) and with the Chalder Fatigue Questionnaire ≥ 16 (scale range 0-33). CONCLUSION: In three commonly used fatigue scales, we have identified cut-off points for clinically significant fatigue among patients recovering from surgery. This can be particularly valuable for diagnostic purposes and in treatment evaluation. Further, it may be possible to analyse and review data from earlier studies in light of clinical relevance.

Development and validation of the Surgical Recovery Scale (SRS).

BACKGROUND: At the present, no fully validated instrument is available for the assessment of general postoperative recovery. Such an instrument would form a useful patient-centered outcome measure in studies evaluating surgical and perioperative interventions. The aim of our study is to develop and validate a summary score based on the Identity Consequence Fatigue Scale (ICFS), for the specific purpose of reliably measuring functional patient recovery following surgery. METHODS: Patients who underwent elective open or laparoscopic colonic resection between June 2006 and June 2009 were included. The 31 item ICFS was administered at baseline and postoperative d 3, 7, 30, and 60. Item reduction was applied based on defined parameters, to derive a single summary score capable of predicting >90% of the variance present in the original ICFS and maximizing sensitivity to changes over time. The final score was then validated against published criteria as set out by Terwee et al. [2]. RESULT: Data from 150 patients were included in the analysis. Application of the item reduction process retained 13 items. These items form the Surgical Recovery Scale (SRS). The SRS was able to predict 94% (89.4%-98.1%) of the ICFS subscale variances, and was successfully validated against seven out of eight published validation criteria. CONCLUSION: The new SRS is a simple and sensitive tool for the assessment of functional recovery following major surgery. Seven of the eight Terwee et al. validation criteria have been addressed, making this the most broadly validated measure of surgical recovery available.

Exploratory study examining barriers to participation in colorectal cancer screening.

OBJECTIVE: To examine the Stage of Change distribution for bowel cancer screening in a regional Australian community and the factors associated with varying positions on the continuum of change. DESIGN: Survey of a convenience sample. SETTING: Community sample. PARTICIPANTS: A total of 59 (31 male, mean age = 59) service club members from a South Australian regional community. MAIN OUTCOME MEASURE: Self-reported Stage of Change for bowel cancer screening behaviour. RESULTS: Attributing greater embarrassment and discomfort to bowel cancer screening was associated with earlier positions on the Stages of Change. Perceiving that bowel cancer screening might have positive value for personal health was associated with more advanced positions on the continuum of change. Those who perceived breast and prostate screening procedures to be embarrassing or to cause discomfort were significantly less likely to be participating in bowel cancer screening. No significant relationships were found between bowel cancer screening Stage of Change and worry about vulnerability; personal, family or wider social network case reports of bowel cancer; and the population-level value attributed to the cancer screening procedures. CONCLUSION: Bowel cancer screening participation rates are currently lower than those associated with breast and prostate screening. Reducing perceptions of embarrassment and discomfort, increasing awareness of potential health benefits and maximising participation in other screening procedures might increase participation in bowel cancer screening.

Using the differential from complete blood counts as a biomarker of fatigue in advanced non-small-cell lung cancer: an exploratory analysis.

OBJECTIVE: Fatigue is currently recognized as an undertreated symptom in cancer. To date the association between fatigue and inflammatory activation has not been examined in patients with advanced cancer. Our exploratory investigation considered whether variations in routinely available hematological parameters relate to the severity of fatigue reports. METHODS: Fatigue, white blood cell differential, and hemoglobin concentration were assessed in 44 Stage IIIb and IV non-small-cell lung cancer (NSCLC) patients. Days of survival and the relative timing of treatment discontinuation were also recorded. Relationships between fatigue intensity and length of survival and between fatigue and hematological variables were examined using binomial and linear regressions respectively. RESULTS: When we controlled for effects related to age, gender, and time until treatment termination, more intense fatigue was associated with shorter survival (beta = -.34, p = .03). Lower hemoglobin concentrations were associated with more intense fatigue (beta = -.36, p = .04). When we controlled for the effect attributable to hemoglobin, higher neutrophil (beta = .43, p = .01) and monocyte (beta = .31, p = .05) concentrations were associated with reports of more severe fatigue. SIGNIFICANCE OF RESULTS: This exploratory study provides empiric data showing that the severity of fatigue reported by advanced-stage NSCLC patients is significantly associated with length of survival. Consistent with existing data, linear regression identified a negative association between fatigue intensity and hemoglobin concentration. When we controlled for this effect, further linear regressions identified significant relationships between fatigue and blood concentrations of neutrophils and monocytes. Further, the magnitude of relationship between myeloid cell concentrations and fatigue was similar to the effect size identified for the relationship between hemoglobin and fatigue. Thus, the indirect measure of inflammatory state provided by routinely assessed myeloid cell counts appears to play as strong a role as the established variable, hemoglobin, in accounting for the fatigue reported by this sample of advanced-stage lung cancer patients.

A prospective study on the influence of a fast-track program on postoperative fatigue and functional recovery after major colonic surgery.

INTRODUCTION: Enhanced Recovery After Surgery (ERAS) programs have demonstrated significant reduction in hospital stay for patients undergoing colonic surgery; however, their impact on long-term outcomes, such as postoperative fatigue (POF), has not been fully established. AIM: To assess the impact of an ERAS program on POF and recovery following elective open colonic surgery. METHOD: In a prospective study, 26 consecutive patients undergoing open colonic surgery under a conventional care plan were compared with 26 consecutive patients in an ERAS program. RESULTS: Demographic and clinical characteristics were comparable at baseline. The median duration of total hospital stay (4 versus 7 d, P < 0.001), rates of urinary tract infections (P = 0.028) and ileus (P = 0.042) were significantly smaller in the ERAS group. Postoperatively, POF significantly increased in both groups. However, peak POF score was significantly lower in the ERAS group (P = 0.001). In the first 30 d after surgery, Fatigue Consequence scores were also significantly smaller in the ERAS group. Overall, the total fatigue experience (P = 0.035) and the total fatigue impact (P = 0.005) were significantly smaller in the ERAS group. CONCLUSION: The impact of ERAS programs may extend beyond the commonly reported short-term outcomes, and ERAS may accelerate overall recovery and return to normal function.

Fatigue after colorectal surgery and its relationship to patient expectations.

BACKGROUND: Feelings of fatigue are pronounced even after uncomplicated abdominal surgery. Patient expectations are associated with a variety of postsurgical outcomes, but few data about fatigue prevalence, nature, and time frame are available for patients and health professionals. Therefore, this study sought to investigate the effect of patient expectations on fatigue experiences following major colorectal surgery. METHODS: Based on the common sense model of illness self-regulation, prior to surgery 51 patients were asked to complete questionnaires assessing their perceptions of likely time frame and ability to control their return to normal functioning after surgery, using subset of questions from the Revised Illness Perceptions Questionnaire. Experience of fatigue and impact of fatigue were also assessed for 2 mo postsurgery using the Identity-Consequences Fatigue Scale. RESULTS: Using mixed model linear regression, baseline depression scores exerted significant main effects on both Fatigue Experiences and Fatigue Impacts scores of the patients. Further, after controlling for depression, there remained significant expectation interactions with both Fatigue Experiences and Fatigue Impacts scores. CONCLUSIONS: Postsurgical fatigue is multidimensional and this should be considered in studies investigating this phenomenon. Patients who before surgery reported shorter expected fatigue resolution time lines and a higher degree of expected control, experienced more persistent fatigue following surgery.

Peritoneal inflammation and fatigue experiences following colorectal surgery: a pilot study.

OBJECTIVE: The effect of post-surgical inflammation, as indicated by peritoneal cytokines and neopterin, was assessed on the duration and characteristics of post-surgical fatigue (PSF) experiences. BACKGROUND: During the weeks following major colorectal surgery, many patients report experiencing substantial fatigue but the physiological factors contributing to this are not well understood. Because cytokines, particularly pro-inflammatory cytokines, have been found to be important in fatigue-related experiences in experimental systems, they may well be important mediators of PSF. METHODS: In 27 patients following colorectal surgery, cytokines and neopterin (a relatively stable immune activation marker) were measured in 24-h peritoneal drain fluid and in serum 2, 5 and 14 days post-operatively. Patient fatigue was assessed using the Identity-Consequence Fatigue Scale questionnaire pre-operatively and 2, 5, 14, 30 and 60 days after surgery. RESULTS: Using linear mixed model analysis controlling for age, gender and ASA score, the trajectory of fatigue experience during the first 2 months of surgical recovery was significantly related to intra-peritoneal concentrations of IL-6, IL-10 and TNF-alpha during the first 24h after surgery, while the trajectory of fatigue impacts was related only to IL-6 and TNF-alpha concentrations. Moreover, correlations between neopterin, and post-operative peritoneal (within 24h of surgery) and serum cytokine concentrations permitted neopterin to be used as a surrogate inflammation marker. Patients with elevated neopterin concentrations during the initial weeks following surgery reported significantly more severe and sustained PSF. CONCLUSIONS: Locally occurring inflammatory responses may influence reports of fatigue following major surgery in a sustained manner, and, as a consequence, reducing inflammation may be effective in reducing PSF.

Differential production of cytokines following colorectal surgery.

BACKGROUND: Colorectal surgery is associated with a number of postoperative complications, including anastomotic leak and local recurrence. These complications are more common after rectal surgery than after colon surgery. Cytokines are secreted into the peritoneal cavity after colorectal surgery and have a number of metabolic and immunological effects. Hence we suggested that differential secretion of these may contribute to the differences in complications between colon and rectal surgeries. METHODS: Patients undergoing either elective rectal excision or colectomy for benign or malignant disease were recruited into the study. The region in relation to the anastomosis was drained with a silastic drain for 12-18 h. Drain fluid was collected on the morning following surgery. The drain fluid was assayed for interleukin (IL)-1beta, tumour necrosis factor-alpha, IL-6, IL-8, IL-10 and IL-13 using multiplexed biomarker immunoassays. RESULTS: Interleukin-8 concentrations were significantly higher in the region of the anastomosis after rectal excision compared with colectomy. Also, IL-6 levels were very high in both groups, but there was no significant difference between the groups. Although the concentrations of IL-10 were higher in the rectal group relative to the colectomy group, only low levels of this cytokine were present in the drain fluids. No other cytokines were consistently detected in significant concentrations. CONCLUSION: This study has shown that the concentration of IL-8 in the region of the anastomosis of patients who have undergone rectal surgery is much higher than those who have undergone colonic surgery. The increased level of IL-8 may provide a milieu conducive to local recurrence and anastomotic leak.

Comprehensive assessment of peri-operative fatigue: development of the Identity-Consequence Fatigue Scale.

OBJECTIVE: Fatigue is one of the complaints most widely reported during peri-operative periods. However, despite its prevalence, the aetiology of this fatigue remains poorly understood. Recent meta-analysis suggests that the limited applicability of existing fatigue measures is contributing to the current lack of understanding. This research therefore sought to use a rigorous analytic process to develop a comprehensive measure of fatigue suitable for use with recovering surgical patients. METHODS: Content analysis was undertaken to investigate the structure of 55 items initially generated. Self-report questionnaires were then distributed to surgical out-patients, and the 177 responses analysed using principal components analysis. Once item selection was finalized, the convergent and discriminant validity of the new measure was assessed. RESULTS: The new measure, the Identity-Consequence Fatigue Scale (ICFS), has 28 items and five subscales. All subscales show high internal reliability, and reentry of deleted items showed that the finalized items form a robust component structure. Discriminant validity analysis confirmed that all ICFS subscales are distinctive from depression and anxiety. Convergent validity analysis confirmed the extent to which the ICFS assesses Fatigue-Consequences is a unique feature of the new measure. CONCLUSION: The ICFS has a clear and stable structure that offers more comprehensive assessment of fatigue than provided by the measures most widely used in postsurgical fatigue (PSF) literature to date.