Children's Use of Electronic Games: Choices of Game Mode and Challenge Levels

Introduction. Interactive electronic games are popular and are believed to contribute to physical activity accrual. The purpose of this study was to examine children's electronic game use during conditions in which they had free access to selecting interactive and seated screen-based versions of electronic games and during the interactive versions had free choice in making adjustments to the activity intensity. Methods. We systematically observed 60 Hong Kong primary school children during two 60-minute game sessions while simultaneously recording their game mode choices and physical activity levels using SOFIT (System for Observing Fitness Instruction Time). Results. When given free choice, children spent more than half of their available time participating in interactive versions of games. These versions of games provided significantly more moderate-to-vigorous physical activity and greater energy expenditure than the computer screen versions. Children with the opportunity to modify intensity levels spent more time playing the interactive versions and accrued more physical activity. Conclusions. The tenets of behavioral choice theory were supported. Access to new-generation interactive games, particularly those with modifiable intensity levels, may facilitate children's participation in physical activity

Measurement invariance of the Functional Assessment of Cancer Therapy—Colorectal quality-of-life instrument among modes of administration

OBJECTIVES: To test for the measurement invariance of the Functional Assessment of Cancer Therapy—Colorectal (FACT-C) in patients with colorectal neoplasms between two modes of administration (self- and interviewer administrations). It is important to establish the measurement invariance of the FACT-C across different modes of administration to ascertain whether it is valid to pool FACT-C data collected by different modes or to assess each group separately. METHODS: A cross-sectional sample of 391 Chinese patients with colorectal neoplasms was recruited from specialist outpatient clinics between September 2009 and July 2010. Confirmatory factor analysis (CFA) was used to test the original five-factor model of the FACT-C on data collected by self- and interviewer administrations in single-group analysis. Multiple-group CFA was then used to compare the factor structure between the two modes of administration using chi-square tests and other goodness-of-fit statistics. RESULTS: The hypothesized five-factor model of FACT-C demonstrated good fit in each group. Configural invariance and metric invariance were fully supported in multiple-group CFA. Some item intercepts and their corresponding error variances were not identical between administration groups, suggesting evidence of partial strict factorial invariance. CONCLUSIONS: Our results confirmed that the five-factor structure of FACT-C was invariant in Chinese patients using both self- and interviewer administrations. It is appropriate to pool or compare data in the emotional well-being and colorectal cancer subscale scores collected by both administrations. Measurement invariance in three items, one from each of the other subscales, may be contaminated by response bias between modes of administration

Patient Empowerment Programme (PEP) in Primary Care Reduced All-cause Mortality and Cardiovascular Diseases in Patients with Type 2 Diabetes Mellitus: A Population-based Propensity Matched Cohort Study

Running title: PEP reduced death and CVD events Clinical trial number and registry: NCT01935349, ClinicalTrials.gov PEP DM CVD Manuscript 20140917 Page 1 of 15 patients treated at primary care outpatient clinics through community trained professional educators. Non-PEP participants were matched one-to-one with the PEP participants using propensity score method with respect to their baseline covariates. Cox proportional hazard regressions were performed to estimate the associations of PEP with the occurrence of first CVD event, coronary heart disease, stroke, heart failure and death from any cause, controlling for baseline characteristics. Conclusions: Enrolment in PEP was associated with reduced all-cause mortality and first CVD events among T2DM patients. The CVD benefit of PEP might be attributable to improving metabolic control through empowerment of self-care and enhancement of quality of diabetes care in primary care. Word Count: 25

The epidemiology and natural history of depressive disorders in Hong Kong's primary care

Background: Depressive disorders are commonly managed in primary care and family physicians are ideally placed to serve as central providers to these patients. Around the world, the prevalence of depressive disorders in patients presenting to primary care is between 10-20%, of which around 50% remain undiagnosed. In Hong Kong, many barriers exist preventing the optimal treatment and management of patients with depressive disorders. The pathways of care, the long term outcomes and the factors affecting prognosis of these patients requires closer examination. Methods/Design. The aim of this study is to examine the prevalence, incidence and natural history of depressive disorders in primary care and the factors influencing diagnosis, management and outcomes using a cross-sectional study followed by a longitudinal cohort study. Doctors working in primary care settings across Hong Kong have been invited to participate in this study. On one day each month over twelve months, patients in the doctor's waiting room are invited to complete a questionnaire containing items on socio-demography, co-morbidity, family history, previous doctor-diagnosed mental illness, recent mental and other health care utilization, symptoms of depression and health-related quality of life. Following the consultation, the doctors provide information regarding presenting problem, whether they think the patient has depression, and if so, whether the diagnosis is new or old, and the duration of the depressive illness if not a new diagnosis. If the doctor detects a depressive disorder, they are asked to provide information regarding patient management. Patients who consent are followed up by telephone at 2, 12, 26 and 52 weeks. Discussion. The study will provide information regarding cross-sectional prevalence, 12 month incidence, remission rate, outcomes and factors affecting outcomes of patients with depressive disorders in primary care. The epidemiology, outcomes, pathways of care, predictors for prognosis and service needs for primary care patients with depressive disorders will be described and recommendations made for policy and service planning. © 2011 Chin et al; licensee BioMed Central Ltd.published_or_final_versio

Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial

Objective To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies