Social Characteristics of Culturally and Linguistically Diverse Cancer Patients Enrolled in Early Phase Clinical Trials in South Western Sydney.

INTRODUCTION: Early phase clinical trials (EPCTs) enable access to novel therapies for patients who have exhausted standard of care treatment and contribute a crucial role in drug development and research. Culturally and linguistically diverse (CALD) or socially disadvantaged patients have notably lower rates of participation in these trials. We aimed to characterise the social and cultural demographics of patients enrolled on an EPCT in South Western Sydney. METHODS: We conducted a 10-year retrospective review of patients enrolled on a EPCT at Liverpool Hospital. CALD patients were defined as those born overseas or whose preferred language was other than English. The patient residential address was used to calculate distance travelled, and the Index of Relative Socioeconomic Disadvantage (IRSD) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) scores were calculated and used as a surrogate for socioeconomic status (SES). RESULTS: Our study included 233 patients across 39 EPCTs. Ninety-one patients (39%) were identified as CALD. The median IRSD and IRSAD scores were 941 and 944, respectively, with 62.7-67.4% of patients residing in an area with greater disadvantage compared to the median of Australia. The median distance travelled was 17 kilometres with only 12% of participants travelling more than 50 km. CALD patients were more likely to reside in an area of low SES (OR 3.4, 95% CI: 1.8-6.5, p < 0.01) and travelled shorter median distances (10 vs. 23 km) when compared to non-CALD patients. CONCLUSION: Our study cohort contained a lower proportion of CALD patients and a higher SES than what we might have expected from our local population. Furthermore, there was a trend toward greater SES disadvantage (lower IRSD/IRSAD scores) for the CALD population. This study provides novel Australian data to support the underrepresentation of culturally diverse or disadvantaged patients on EPCTs. Future efforts should be made to reduce barriers to participation and improve equity in clinical trial participation.

The Prognostic and Predictive Utility of CDX2 in Colorectal Cancer.

Caudal type homeobox transcription factor 2 (CDX2) is a gastrointestinal cancer biomarker that regulates epithelial development and differentiation. Absence or low levels of CDX2 have been associated with poor prognosis and proposed as a chemotherapy response predictor. Tumour tissue samples from 668 patients with stage I-IV colorectal cancer were stained for CDX2 and stratified into two subgroups according to expression levels. Statistical tests were used to evaluate CDX2's relationship with survival and chemotherapy response. Of 646 samples successfully stained, 51 (7.9%) had low CDX2 levels, and 595 (92.1%) had high levels. Low CDX2 staining was associated with poor differentiation and the presence of lymphovascular or perineural invasion and was more common in colon and right-sided tumours. Overall survival (p < 0.001) and disease-free survival (p = 0.009) were reduced in patients with low CDX2 expression. Multivariable analysis validated CDX2 as an independent poor prognostic factor after excluding confounding variables. There was no statistically significant improvement in survival with adjuvant chemotherapy in stage II colon cancer (p = 0.11). In the rectal cohort, there was no relationship between CDX2 levels and therapy response. While confirming the prognostic utility of CDX2 in colorectal cancer, our study highlights that larger studies are required to confirm its utility as a predictive chemotherapy biomarker, especially in left-sided and rectal cancers.

Microsatellite Instability Testing and Prognostic Implications in Colorectal Cancer.

Given the crucial predictive implications of microsatellite instability (MSI) in colorectal cancer (CRC), MSI screening is commonly performed in those with and at risk for CRC. Here, we compared results from immunohistochemistry (IHC) and the droplet digital PCR (ddPCR) MSI assay on formalin-fixed paraffin-embedded tumor samples from 48 patients who underwent surgery for colon and rectal cancer by calculating Cohen's kappa measurement (k), revealing high agreement between the methods (k = 0.915). We performed Kaplan-Meier survival analyses and univariate and multivariate Cox regression to assess the prognostic significance of ddPCR-based MSI and to identify clinicopathological features associated with CRC outcome. Patients with MSI-high had better overall survival (OS; p = 0.038) and disease-free survival (DFS; p = 0.049) than those with microsatellite stability (MSS). When stratified by primary tumor location, right-sided CRC patients with MSI-high showed improved DFS, relative to those with MSS (p < 0.001), but left-sided CRC patients did not. In multivariate analyses, MSI-high was associated with improved OS (hazard ratio (HR) = 0.221, 95% confidence interval (CI): 0.026-0.870, p = 0.042), whereas the loss of DNA mismatch repair protein MutL homolog 1 (MLH1) expression was associated with worse OS (HR = 0.133, 95% CI: 0.001-1.152, p = 0.049). Our results suggest ddPCR is a promising tool for MSI detection. Given the opposing effects of MSI-high and MLH1 loss on OS, both ddPCR and IHC may be complementary for the prognostic assessment of CRC.

Comparison of Prognostic Scores in Early Phase Clinical Trials: A 10-year Single Centre Australian Experience.

BACKGROUND/AIM: Early phase clinical trials (EPCTs) assess the tolerability of novel anti-cancer therapeutics in patients with advanced malignancy. Patient selection is important given the modest clinical benefit and time commitments for trials. Prognostic scores have been developed to facilitate identification of high-risk patients. This study aimed to compare five prognostic scores to predict survival for patients on an EPCT. PATIENTS AND METHODS: We performed a retrospective review of patients enrolled in EPCT at Liverpool Hospital, Sydney, from 2013 to 2023. Demographic, biochemical, and survival data were collected from electronic medical records. The score from five prognostic scoring systems (Royal Marsden hospital, MD Anderson Cancer centre, Gustave Roussy Immune, MD Anderson Immune Checkpoint Inhibitor and Princess Margaret Hospital Index) were calculated. Overall survival was measured using the Kaplan-Meier method and predictive discrimination was assessed using Harrell's c-index. RESULTS: A total of 218 patients across 36 EPCTs were included. The median overall survival was 9.8 months with 22% of patients dying in less than 90 days. Seventeen to thirty-four percent of patients were categorised as high-risk. The MDACC score obtained the highest predictability for overall survival for the whole cohort (c-index=0.67, 95%CI=0.62-0.72) and the immunotherapy-based cohort (c-index= 0.65, 95%CI=0.59-0.71). However, all scores performed similarly with a significant overlap in the confidence intervals. CONCLUSION: Our retrospective audit confirms the utility of prognostic scores to predict survival in an Australian EPCT cohort, with similar predictive discrimination across various scoring systems. Integration of these prognostic tools into EPCT screening processes may optimise benefits and reduce risks associated with EPCTs.

Real-world tolerance and outcomes of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer-Does dose intensity matter?

INTRODUCTION: Fluoropyrimidine and oxaliplatin-based adjuvant chemotherapy delivered as 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), or capecitabine and oxaliplatin (CAPOX) is the standard of care for resected stage III colon cancer. Without randomized trial data, we compared real-world dose intensity, survival outcomes, and tolerability of these regimens. METHODS: Records of patients treated with FOLFOX or CAPOX in the adjuvant setting for stage III colon cancer across four institutions in Sydney during 2006-2016 were reviewed. The relative dose intensity (RDI) of fluoropyrimidine and oxaliplatin of each regimen, disease-free survival (DFS), overall survival (OS), and incidence of grade ≥2 toxicities were compared. RESULTS: Characteristics of patients receiving FOLFOX (n = 195) and CAPOX (n = 62) were evenly matched. FOLFOX patients had a higher mean RDI for both fluoropyrimidine (85% vs. 78%, p < 0.01) and oxaliplatin (72% vs. 66%, p = 0.06). In spite of a lower RDI, CAPOX patients trended toward a better 5-year DFS (84% vs. 78%, HR = 0.53, p = 0.068) and similar OS (89% vs. 89%, HR = 0.53, p = 0.21) compared to the FOLFOX group. This difference was most pronounced in the high-risk (T4 or N2) group where 5-year DFS was 78% versus 67% (HR = 0.41, p = 0.042). Patients receiving CAPOX experienced more grade ≥2 diarrhea (p = 0.017) and hand-foot syndrome (p < 0.001) but not peripheral neuropathy or myelosuppression. CONCLUSION: In a real-world setting, patients who received CAPOX had similar OS rates when compared to those receiving FOLFOX in the adjuvant setting in spite of lower RDI. In the high-risk population, CAPOX appears to demonstrate a superior 5-year DFS over FOLFOX.

KRAS and BRAF Mutation Rates and Survival Outcomes in Colorectal Cancer in an Ethnically Diverse Patient Cohort.

KRAS and BRAF mutation rates in colorectal cancer (CRC) reported from various mono-ethnic studies vary amongst different ethnic groups. However, these differences in mutation rates may not be statistically significant or may be due to differences in environmental and/or laboratory factors across countries rather than racial genetic differences. Here, we compare the KRAS/BRAF mutation rates and survival outcomes in CRC between ethnic groups at a single institution. We also investigate the contributions of genetic, environmental, and laboratory factors to the variations in KRAS/BRAF mutation rates reported from different countries. Clinicopathological data from 453 ethnically diverse patients with CRC were retrospectively analyzed at Liverpool Hospital, NSW Australia (2014-2016). KRAS/BRAF mutations were detected using real-time PCR (Therascreen kits from Qiagen). Mismatch repair (MMR) status was determined using immunohistochemical staining. Four ethnic groups were analyzed: Caucasian, Middle Eastern, Asian, and South American. Overall survival data were available for 406 patients. There was no significant difference in KRAS mutation rates between Caucasians (41.1%), Middle Easterners (47.9%), Asians (44.8%), and South Americans (25%) (p = 0.34). BRAF mutation rates differed significantly between races (p = 0.025), with Caucasians having the highest rates (13.5%) and Middle Easterners the lowest (0%). A secondary analysis in which Caucasians were divided into three subgroups showed that ethnic grouping correlated significantly with KRAS mutation rate (p = 0.009), with central and eastern Europeans having the highest rates (58.3%). There were no significant differences in overall survival (OS) or disease-free survival (DFS) between the four races. The similarity in KRAS mutation rates across races raises the possibility that the differences in KRAS mutation rates reported from various countries may either not be statistically significant or may be due to environmental and/or laboratory factors rather than underlying racial genetic differences. In contrast, we verified that BRAF mutation rates differ significantly between races, suggesting racial genetic differences may be responsible for the discrepant BRAF mutation rates reported from different countries.

Multigene panel next generation sequencing in metastatic colorectal cancer in an Australian population.

BACKGROUND: Next generation sequencing (NGS) is increasingly used in standard clinical practice to identify patients with potentially actionable mutations. Stratification of NGS mutation tiers is currently based on the European Society of Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT[E]) Tier I-V & X. Allele frequency is also increasingly recognised as an important prognostic tool in advanced cancer. The aim of this study was to determine the genomic mutations in metastatic colorectal cancer (CRC) in an Australian multicultural population and their influence on survival outcomes. METHODS: Next generation sequencing with the 50-gene panel Oncomine Precision Assay™ was used on 180 CRC tissue samples obtained across six Sydney hospitals between June 2021 and March 2022. RESULTS: From 180 samples, 147 (82%) had at least one gene mutation identified with 68 (38%) having two or more concurrent mutations. Tier I variants included RAS wild-type [EI] in 73 (41%) and BRAF V600E [EIA] in 27 (15%). Non-tier I variants include 2 (1%) ERBB2 amplification [EIIB], 26 (15%) PIK3CA hotspot mutations [EIIIA] and 9 (5%) MET focal amplifications [EIIIA]. NGS testing revealed an additional 22% of cases with Tier II & III mutations. 43% of patients also presented with potentially actionable Tier III & IV mutations. Patients with concurrent TP53 and RAS mutations had significantly reduced overall survival (6.1 months versus 21.1 months, p <0.01). High KRAS allele frequency, as defined by those with over 20% variant allele frequency (VAF), also demonstrated reduced overall survival (12.1 months versus 42.9 months, p = 0.04). CONCLUSIONS: In addition to identifying patients with genomic alterations suitable for clinically proven standard of care therapeutic options, the 50 gene NGS panel has significant potential in identifying potentially actionable non-tier 1 mutations and therefore may become future standard clinical practice.

Post-acute sequelae of COVID-19 and longitudinal antibody levels in a community-based cohort.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection invokes variable immune responses and poses a risk of post-acute sequelae SARS-CoV-2 infection (PASC) symptoms; however, most data on natural history are derived from patients with severe infection. Further data are needed among patients with mild infection, who comprise most cases. METHODS: The Dallas Fort-Worth (DFW) COVID-19 Prevalence Study included 21,597 community-dwelling adults (ages 18-89) who underwent COVID-19 PCR and anti-nucleocapsid antibody testing between July 2020 and March 2021. We invited participants with positive COVID-19 results (cases) and a subset with negative results (controls), matched on age, sex, race/ethnicity, and ZIP code, to complete a follow-up questionnaire for PASC symptoms and repeat anti-nucleocapsid testing, and anti-spike antibody testing between July and December 2021. RESULTS: Of 3,917 adults invited to participate, 2260 (57.7%) completed the questionnaire- 1150 cases and 1110 controls. Persistent symptoms were reported in 21.1% of cases, with the most common being shortness of breath, fatigue, and loss of taste or smell. Among 292 cases with asymptomatic infection, >15% reported new fatigue and 8-10% reported new loss of taste/smell, myalgias, or headache. Median anti-nucleocapsid levels in cases decreased from 3.5U to 0.7U over a median follow-up of 8.6 months. Anti-spike antibody levels at 6-7 months post-vaccination in cases were similar to that of controls. CONCLUSIONS: More than 1 in 5 patients with COVID-19 infection, including those with mild infection, reported persistent symptoms during follow-up. Both nucleocapsid and spike protein antibody levels decreased within six months following a COVID-19 infection and vaccination.

Randomized trial of personalized psychological feedback from a longitudinal online survey and simultaneous evaluation of randomized stepped wedge availability of in-person peer support for hospital staff during the COVID-19 pandemic.

OBJECTIVE: We tested if automated Personalized Self-Awareness Feedback (PSAF) from an online survey or in-person Peer Resilience Champion support (PRC) reduced emotional exhaustion among hospital workers during the COVID-19 pandemic. METHOD: Among a single cohort of participating staff from one hospital organization, each intervention was evaluated against a control condition with repeated measures of emotional exhaustion at quarterly intervals for 18 months. PSAF was tested in a randomized controlled trial compared to a no-feedback condition. PRC was tested in a group-randomized stepped-wedge design, comparing individual-level emotional exhaustion before and after availability of the intervention. Main and interactive effects on emotional exhaustion were tested in a linear mixed model. RESULTS: Among 538 staff, there was a small but significant beneficial effect of PSAF over time (p = .01); the difference at individual timepoints was only significant at timepoint three (month six). The effect of PRC over time was non-significant with a trend in the opposite direction to a treatment effect (p = .06). CONCLUSIONS: In a longitudinal assessment, automated feedback about psychological characteristics buffered emotional exhaustion significantly at six months, whereas in-person peer support did not. Providing automated feedback is not resource-intensive and merits further investigation as a method of support.

Relationship between three aspects of resilience-adaptive characteristics, withstanding stress, and bouncing back-in hospital workers exposed to prolonged occupational stress during the COVID-19 pandemic: a longitudinal study.

BACKGROUND: The term resilience is used to refer to multiple related phenomena, including: (i) characteristics that promote adaptation to stressful circumstances, (ii) withstanding stress, and (iii) bouncing back quickly. There is little evidence to understand how these components of resilience are related to one another. Skills-based adaptive characteristics that can respond to training (as opposed to personality traits) have been proposed to include living authentically, finding work that aligns with purpose and values, maintaining perspective in the face of adversity, managing stress, interacting cooperatively, staying healthy, and building supportive networks. While these characteristics can be measured at a single time-point, observing responses to stress (withstanding and bouncing back) require multiple, longitudinal observations. This study's aim is to determine the relationship between these three aspects of resilience in hospital workers during the prolonged, severe stress of the COVID-19 pandemic. METHODS: We conducted a longitudinal survey of a cohort of 538 hospital workers at seven time-points between the fall of 2020 and the spring of 2022. The survey included a baseline measurement of skills-based adaptive characteristics and repeated measures of adverse outcomes (burnout, psychological distress, and posttraumatic symptoms). Mixed effects linear regression assessed the relationship between baseline adaptive characteristics and the subsequent course of adverse outcomes. RESULTS: The results showed significant main effects of adaptive characteristics and of time on each adverse outcome (all p < .001). The size of the effect of adaptive characteristics on outcomes was clinically significant. There was no significant relationship between adaptive characteristics and the rate of change of adverse outcomes over time (i.e., no contribution of these characteristics to bouncing back). CONCLUSIONS: We conclude that training aimed at improving adaptive skills may help individuals to withstand prolonged, extreme occupational stress. However, the speed of recovery from the effects of stress depends on other factors, which may be organizational or environmental.

Prognostic Significance of MRE11 Overexpression in Colorectal Cancer Patients.

Meiotic recombination 11 (MRE11) plays a critical role in the DNA damage response and maintenance of genome stability and is associated with the prognosis for numerous malignancies. Here, we explored the clinicopathological significance and prognostic value of MRE11 expression in colorectal cancer (CRC), a leading cause of cancer-related deaths worldwide. Samples from 408 patients who underwent surgery for colon and rectal cancer between 2006 and 2011, including a sub-cohort of 127 (31%) patients treated with adjuvant therapy, were analyzed. In Kaplan-Meier survival analyses, we found that high MRE11 expression in the tumor center (TC) was significantly associated with poor disease-free survival (DFS; p = 0.045) and overall survival (OS; p = 0.039). Intriguingly, high MRE11 expression in the TC was also significantly correlated with reduced DFS (p = 0.005) and OS (p = 0.010) in the subgroup with right-sided primary CRC. In multivariate analyses, high MRE11 expression (hazard ratio [HR] = 1.697, 95% confidence interval [CI]: 1.034-2.785; p = 0.036) and lymphovascular/perineural invasion (LVI/PNI; HR = 1.922, 95% CI 1.122-3.293; p = 0.017) showed significant association with worse OS in patients with right-sided tumors but not those with left-sided tumors. Moreover, in patients with right-sided tumors, high MRE11 was associated with worse OS for those with lymph node involvement (p = 0.006) and LVI/PNI (p = 0.049). Collectively, our results suggest that MRE11 may serve as an independent prognostic marker in those with right-sided severe CRC, with clinical value in the management of these patients.

A phase 1 dose-escalation study of the poly(ADP-ribose) polymerase inhibitor senaparib in Australian patients with advanced solid tumors.

BACKGROUND: Senaparib is a novel, selective poly(ADP-ribose) polymerase-1/2 inhibitor with strong antitumor activity in preclinical studies. This first-in-human, phase 1, dose-escalation study examined the safety and preliminary efficacy of senaparib in patients with advanced solid tumors. METHODS: Patients with advanced solid tumors were enrolled from three centers in Australia, using a conventional 3 + 3 design. Dose-escalation cohorts continued until the maximum tolerated dose or a recommended phase 2 dose was determined. Patients received one dose of oral senaparib and, if no dose-limiting toxicity occurred within 7 days, they received senaparib once daily in 3-week cycles. The primary end points were safety and tolerability. RESULTS: Thirty-nine patients were enrolled at 10 dose levels ranging from 2 to 150 mg. No dose-limiting toxicities were observed in any cohort. Most treatment-emergent adverse events were grade 1-2 (91%). Seven patients (17.9%) reported hematologic treatment-emergent adverse events. Treatment-related adverse events occurred in eight patients (20.5%), and the most frequent was nausea (7.7%). Two deaths were reported after the end of study treatment, one of which was considered a complication from senaparib-related bone marrow failure. Pharmacokinetic analysis indicated that senaparib the accumulation index was 1.06-1.67, and absorption saturation was 80-150 mg daily. In 22 patients with evaluable disease, the overall response rate was 13.6%, and the disease control rate was 81.8%. The overall response rate was 33.3% for the BRCA mutation-positive subgroup and 6.3% for the nonmutated subgroup. CONCLUSIONS: Senaparib was well tolerated in Australian patients with advanced solid tumors, with encouraging signals of antitumor activity. The recommended phase 2 dose for senaparib was determined to be 100 mg daily. GOV ID: NCT03507543.

Perceptions of How Education Has Prepared UK Veterinary Nurses for Their Professional Role.

Assessing how prepared individuals are for a career pathway is essential if job satisfaction and retention are to be considered within an industry. Determining how training prepares registered veterinary nurses (RVNs) will therefore provide employers and educators with valuable information about how education is meeting expectations and demands. A positivist, quantitative approach led to a cross-sectional study via an online questionnaire reaching 141 RVNs. Participants were demographically profiled prior to differences being determined between data sets using the Kruskal-Wallis H and Mann-Whitney U tests. All educational routes and job roles generated different scores for preparedness for the duties carried out; however, the main differences were between degree and diploma routes, with diploma-route students suggesting that they were prepared in more subject areas. A variety of qualification routes are available to a veterinary nurse in the UK, which must be considered when reviewing preparedness and making suggestions for educational reform. Further research is needed to support these findings in relation to the roles of the educator, the employer, and the veterinary nurse to allow for an unbiased understanding of preparedness, which could have links to job satisfaction.

Reduced critical care demand with early CPAP and proning in COVID-19 at Bradford: A single-centre cohort.

Background: Guidance in COVID-19 respiratory failure has favoured early intubation, with concerns over the use of CPAP. We adopted early CPAP and self-proning, and evaluated the safety and efficacy of this approach. Methods: This retrospective observational study included all patients with a positive COVID-19 PCR, and others with high clinical suspicion. Our protocol advised early CPAP and self-proning for severe cases, aiming to prevent rather than respond to deterioration. CPAP was provided outside critical care by ward staff supported by physiotherapists and an intensive critical care outreach program. Data were analysed descriptively and compared against a large UK cohort (ISARIC). Results: 559 patients admitted before 1 May 2020 were included. 376 were discharged alive, and 183 died. 165 patients (29.5%) received CPAP, 40 (7.2%) were admitted to critical care and 28 (5.0%) were ventilated. Hospital mortality was 32.7%, and 50% for critical care. Following CPAP, 62% of patients with S:F or P:F ratios indicating moderate or severe ARDS, who were candidates for escalation, avoided intubation. Figures for critical care admission, intubation and hospital mortality are lower than ISARIC, whilst critical care mortality is similar. Following ISARIC proportions we would have admitted 92 patients to critical care and intubated 55. Using the described protocol, we intubated 28 patients from 40 admissions, and remained within our expanded critical care capacity. Conclusion: Bradford's protocol produced good results despite our population having high levels of co-morbidity and ethnicities associated with poor outcomes. In particular we avoided overloading critical care capacity. We advocate this approach as both effective and safe.

Rectal cancer treatment and outcomes in elderly patients treated with curative intent.

The elderly population comprises a significant proportion of patients diagnosed with rectal cancer. However, there is a lack of evidence to guide treatment decisions in this group. Thus, this multicentre study compares the histopathology, treatment patterns and outcomes between the elderly and young populations with non-metastatic rectal cancer. The present study reported on the clinicopathological variables, treatment modalities and survival outcomes in 736 patients diagnosed with non-metastatic rectal cancer between 2006 and 2015. Patients were divided into the following two groups, <70 and ≥70 years of age, which were compared using Chi-square and survival outcome analysis using Kaplan-Meier. Elderly patients made up nearly half of the cohort and were less likely to undergo trimodality therapy or be discussed in a multidisciplinary meeting. Surgery in the elderly patients was associated with increased mortality. Elderly patients had worse cancer-specific survival (75 vs. 85%), which was particularly evident in stage III disease (hazard ratio, 2.1). Elderly patients in this subgroup treated with trimodality therapy had similar survival outcomes to younger patients. Elderly patients with locally advanced rectal cancer comprise a large proportion of the patient cohort. Consideration should be given for trimodality therapy in this group, taking into account biological age, especially in the context of increasing life expectancy and improvement in the management of age-related comorbidities.

Measurement properties of the simplified Chinese version of Nonrestorative Sleep Scale in adolescents.

This study aimed to assess the measurement properties of a simplified Chinese version of the Nonrestorative Sleep Scale (NRSS) among adolescents. We obtained a simplified Chinese NRSS by the standard forward-backward translation procedures and administered it to 486 students who were attending Grade 7-11 in Nanjing, China. Furthermore, Pittsburgh Sleep Quality Index, Athens Insomnia Scale, Centre for Epidemiological Studies Depression Scale, and Toronto Hospital Alertness Test were also self-completed for measuring sleep quality, insomnia, depression and alertness respectively. The sample was randomly split into two halves, with the first half used to explore the scale structure by exploratory factor analysis (EFA), and the second half used to confirm the identified structure by confirmatory factor analysis (CFA). A total of 481 adolescents (49% male) with a mean age of 16 years (range: 13-18) completed this study. In the other half of 250 adolescents, the root mean square error of approximation (RMSEA), standardised root mean square residual, and comparative fit index (CFI) in CFA, which tested the four-factor structure obtained from EFA, were 0.062, 0.051 and 0.975, respectively. Convergent validity was demonstrated from a significant correlation of the simplified Chinese NRSS with sleep quality (r = -0.62), insomnia (r = -0.71), depression (r = -0.60) and alertness (r = 0.54). The internal consistency and test-retest reliability for the global scale were 0.83 and 0.86 respectively. Measurement invariance was established between males and females with the changes of both CFI and RMSEA < 0.01. The simplified Chinese NRSS is valid and reliable for measuring NRS among Chinese adolescents.

Tumour immune microenvironment biomarkers predicting cytotoxic chemotherapy efficacy in colorectal cancer.

The role of the local tumour and stromal immune landscape is increasingly recognised to be important in cancer development, progression and response to therapy. The composition, function, spatial orientation and gene expression profile of the infiltrate of the innate and adaptive immune system at the tumour and surrounding tissue has an established prognostic role in colorectal cancer (CRC). Multiple studies have confirmed that a tumour immune microenvironment (TIME) reflective of a type 1 adaptive immune response is associated with improved prognosis. There have been significant efforts to evolve these observations into validated, histopathology-based prognostic biomarkers, such as the Immunoscore. However, the clinical need lies much more in the development of predictive, not prognostic, biomarkers which have the potential to improve patient outcomes. This is particularly pertinent to help guide cytotoxic chemotherapy use in CRC, which remains the standard of care. Cytotoxic chemotherapy has recognised immunomodulatory activity distinct from its antimitotic effects, including mechanisms such as immunogenic cell death (ICD) and induction/inhibition of key immune players. Response to chemotherapy may differ with regard to molecular subtype of CRC, which are strongly associated with immune phenotypes. Thus, immune markers are potentially useful, though under-reported, predictive biomarkers. In this review, we discuss the impact of the TIME on response to cytotoxic chemotherapy in CRC, with a focus on baseline immune markers, and associated genomic and transcriptomic signatures.

Physical behaviors and fundamental movement skills in British and Iranian children: An isotemporal substitution analysis.

Although the relationship between fundamental movement skills (FMS) and physical behaviors has been established, differences between countries are scarcely explored. The impact of the whole physical behavior composition, in relation to FMS, has yet to be investigated in 9-11 y children. The aims were to investigate the associations of substitution of physical behaviors with FMS score and to compare traditional linear regression and compositional data analysis and compare between England and Iran. Measures included accelerometer-derived activity (sleep (SL), sedentary behavior (SB), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) and FMS, using the TGMD-2, in 119 children (64 boys) from Iran (mean (±SD) age: 9.8 ± 0.3 y; BMI of 18.2 ± 3.3 kg/m2 ) and 139 (61 boys) children from England (mean (±SD) age: 9.5 ± 0.6 y; BMI of 17.7 ± 3.1 kg/m2 ). Isometric log-ratio multiple linear regression models were used to discern the association between FMS and the mean activity composition, and for new compositions, where fixed durations of time were reallocated from one behavior to another, while the remaining behaviors were unchanged. In physical behaviors as a composition, FMS was significantly associated in both ethnicities. English children responded significantly positively to adding 5 or more minutes LPA at the expense of SB (FMS unit change from 0.05 [0.01, 0.09] at 5 minutes to 0.72 [0.01, 1.34] at 60 minutes). Adding 10 minutes or more of SL, at the expense of SB, was associated with a significant, positive change in FMS in all children. Investigation is needed to understand the composition of SB and its potential influence on FMS development.

Psychometric evaluation of the Chinese version of the Toronto Hospital Alertness Test.

BACKGROUND: Alertness is an important part of attention which is different from the opposite of sleepiness. This study aimed to translate and assess the measurement properties of the Toronto Hospital Alertness Test (THAT) in Hong Kong Chinese population. METHODS: The standard forward-backward translation procedure and cognitive debriefing were conducted to obtain the Chinese THAT. One hundred Chinese adults completed the Chinese THAT, the Center for Epidemiological Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Athens Insomnia Scale (AIS) by telephone interviews. RESULTS: The factorial validity was assessed by confirmatory factor analysis, and the internal reliability was examined by coefficient omega. The two negatively worded items of the THAT had low factor loadings and were removed. One more item was removed based on the modification indices of the eight-item model. The remaining seven-item THAT showed satisfactory unidimensionality with root mean square error of approximation (RMSEA) = 0.06, standardized root mean square residual (SRMR) = 0.08, and comparative fit index (CFI) = 1.00. The coefficient omega of the seven-item Chinese THAT was 0.80 (95% CI: 0.74-0.86). Convergent validity was demonstrated with THAT moderately associated with CES-D (r = - 0.45, P < 0.01), PSQI (r = - 0.40, P < 0.01), and AIS (r = - 0.45, P < 0.01). CONCLUSIONS: The Chinese version of THAT demonstrated acceptable reliability and validity in a Chinese population.