Metronomic gemcitabine suppresses tumour growth, improves perfusion, and reduces hypoxia in human pancreatic ductal adenocarcinoma.

BACKGROUND: The current standard of care for pancreatic cancer is weekly gemcitabine administered for 3 of 4 weeks with a 1-week break between treatment cycles. Maximum tolerated dose (MTD)-driven regimens as such are often associated with toxicities. Recent studies demonstrated that frequent dosing of chemotherapeutic drugs at relatively lower doses in metronomic regimens also confers anti-tumour activity but with fewer side effects. METHODS: Herein, we evaluated the anti-tumour efficacy of metronomic vs MTD gemcitabine, and investigated their effects on the tumour microenvironment in two human pancreatic cancer xenografts established from two different patients. RESULTS: Metronomic and MTD gemcitabine significantly reduced tumour volume in both xenografts. However, K(trans) values were higher in metronomic gemcitabine-treated tumours than in their MTD-treated counterparts, suggesting better tissue perfusion in the former. These data were further supported by tumour-mapping studies showing prominent decreases in hypoxia after metronomic gemcitabine treatment. Metronomic gemcitabine also significantly increased apoptosis in cancer-associated fibroblasts and induced greater reductions in the tumour levels of multiple pro-angiogenic factors, including EGF, IL-1alpha, IL-8, ICAM-1, and VCAM-1. CONCLUSION: Metronomic dosing of gemcitabine is active in pancreatic cancer and is accompanied by pronounced changes in the tumour microenvironment.

Activity Participation and Perceived Health Status in Patients with Severe Mental Illness: a Prospective Study.

OBJECTIVE: To examine associations between severe mental illness (SMI), general health symptoms, mental wellbeing, and different activity levels in patients with SMI. METHOD: Consecutive patients with SMI referred for occupational therapy were prospectively included. Their hours of activities per day during hospital stay were recorded as <1 hour, 1-3 hours, and >3 hours in three categories: basic self-care activities, interest-based activities, and role-specific activities. Patients were free to join or decline any activities. Patients' somatic and mental health were measured at admission, discharge, and 1 month after discharge using the Brief Psychiatric Rating Scale (BPRS), Patient Health Questionnaire-15 (PHQ-15), Pittsburgh Sleep Quality Index (PSQI), Chinese version of Short Warwick Edinburgh Mental Wellbeing Scale (C-SWEMWBS), and Chinese version of General Activity Motivation Measure (GAMM). RESULTS: 84 patients (35 men and 49 women) aged 16 to 63 years were assessed at the three timepoints. The mean length of hospital stay of current admission was 74.73 days. The most common diagnosis was schizophrenia (n=35), followed by depression (n=15), psychosis (n=14), bipolar affective disorder (n=10), others (n=8), and delusional disorder (n=2). The hours of activities per day was <1 hour in 32 (38.1%) patients, 1-3 hours in 34 (40%) patients, and >3 hours in 18 (21.2%) patients. Improvement in somatic and mental health was positively associated with hours of activities per day. Activities were associated with reduced psychiatric symptoms (measured by BPRS) at discharge (Z = 5.978, p < 0.01). Activities were associated with less somatic complaints (measured by PHQ-15) [χ2 = 23.478, p < 0.01], better sleep quality (measured by PSQI) [χ2 = 14.762, p < 0.01]. The BPRS score for psychiatric symptoms at discharge was inversely associated with C-SWEMWBS score for mental wellbeing (r = -0.233, p = 0.033) and C-GAMM score for activity motivation (r = -0.258, p = 0.018). Basic self-care activities were a predictor for psychiatric symptoms (measured by BPRS) at discharge (adjusted R2 = 0.091, F = 8.496, p = 0.005), whereas a combined group of badminton and Tai Chi was a predictor for general activity motivation (measured by GAMM) at 1 month after discharge (adjusted R2 = 0.047, F = 4.697, p < 0.05), and soccer alone was a predictor for somatic health (measured by PHQ-15) at 1 month after discharge (adjusted R2 = 0.06, F = 5.784, p < 0.05). CONCLUSION: Participating in activities of patients' own choice and interests is positively associated with patients' psychiatric and somatic health and subjective wellbeing. Outdoor soccer has added effect on patients' somatic health. The beneficial effects are maintained at 1 month after discharge. Daily participation of activity meaningful to patients can be a non-pharmacological treatment for patients with SMI to improve somatic and mental health.

Concurrent validation of a neurocognitive assessment protocol for clients with mental illness in job matching as shop sales in supported employment.

OBJECTIVES: Occupational therapists play a major role in the assessment and referral of clients with severe mental illness for supported employment. Nonetheless, there is scarce literature about the content and predictive validity of the process. In addition, the criteria of successful job matching have not been analysed and job supervisors have relied on experience rather than objective standards in recruitment. This study aimed to explore the profile of successful clients working in 'shop sales' in a supportive environment using a neurocognitive assessment protocol, and to validate the protocol against 'internal standards' of the job supervisors. METHODS: This was a concurrent validation study of criterion-related scales for a single job type. The subjective ratings from the supervisors were concurrently validated against the results of neurocognitive assessment of intellectual function and work-related cognitive behaviour. RESULTS: A regression model was established for clients who succeeded and failed in employment using supervisor's ratings and a cutoff value of 10.5 for the Performance Fitness Rating Scale (R(2) = 0.918, F[41] = 3.794, p = 0.003). Classification And Regression Tree was also plotted to identify the profile of cases, with an overall accuracy of 0.861 (relative error, 0.26). CONCLUSION: Use of both inference statistics and data mining techniques enables the decision tree of neurocognitive assessments to be more readily applied by therapists in vocational rehabilitation, and thus directly improve the efficiency and efficacy of the process.

Thalidomide, an antiangiogenic agent with clinical activity in cancer.

Despite the teratogenic past of thalidomide, there is recent evidence indicating the drug's efficacy in the management of various diseases from immune disorders to cancers. The history, pharmacodynamic and pharmacokinetic properties of thalidomide in the clinic are discussed in this review article.

Translation and validation of the Chinese version of the short Warwick-Edinburgh Mental Well-being Scale for patients with mental illness in Hong Kong.

OBJECTIVE: Quality of life outcomes are useful in the assessment of mental and social wellbeing and for informed health care decision-making, especially in the choice of interventions in psychiatric rehabilitation. In its original form, the Warwick-Edinburgh Mental Well-being Scale (WEMWBS) is a proven reliable and valid tool for assessing quality of life in normal adults, but not in adults from Asian countries. A shortened 7-item version of WEMWBS (SWEMWBS) with good internal construct validity was used for this study. The present study describes the translation of WEMWBS from English to Chinese and its validation in a sample of Chinese-speaking patient population. METHODS: Participants included patients admitted to the inpatient units, and those attending the day hospital and outpatient units of the Kowloon Hospital (n = 126). Translation was performed using the multiple forward and backward translation protocol. Patients also completed the 5-item World Health Organization Well-being Index (WHO5) questionnaire. A case therapist completed the Brief Psychiatric Rating Scale within 2 days. A total of 20 patients were selected for test-retest measurements performed after 2 weeks. RESULTS: The sample displayed a normal distribution of the Chinese version of SWEMWBS (C-SWEMWBS) scores (mean ± standard deviation, 23.16 ± 5.39; skewness, -0.068; kurtosis, -0.355). Internal reliability coefficient (Cronbach's alpha) for C-SWEMWBS was 0.89 which was consistent with that of English version. The corrected item-total correlation was high with Spearman's rank correlation coefficients ranging from 0.57 (item 6) to 0.75 (item 5). Good test-retest reliability was observed (r = 0.677; p = 0.001). Principal components factor analysis identified a single component (eigenvalues, 4.28; 61.1% variance), similar to the English version. Scores of C-SWEMWBS were positively correlated with the scores of WHO5 (r = 0.49; p < 0.001), suggesting good concurrent validity. Few item scores including 'feeling useful', 'dealing with problems well', 'able to make decisions', and the total score were significantly correlated with diagnostic groups (p < 0.05). Education and diagnosis of mental illness were valid predictors for C-SWEMWBS (F = 5.41; p = 0.01). There were no effects due to age and gender. CONCLUSION: The C-SWEMWBS showed high levels of internal consistency and reliability against accepted criteria. It is short, acceptable, and culturally meaningful to clients with mental illness. Further large-scale studies in normal subjects and varied patient groups are recommended to generalise the findings.

Development and validation of the interview version of the Hong Kong Chinese WHOQOL-BREF.

INTRODUCTION: The Hong Kong Chinese version of the WHOQOL-BREF was designed as a self-administered questionnaire and has limitations in clinical application on subjects who have limitations in reading or writing. An interview version is therefore needed to avoid sampling biases in clinical studies. Since there are significant differences in the written Chinese and spoken Cantonese, which is a dialect commonly spoken among people in Hong Kong, and adaptation process for converting the written Chinese into spoken Cantonese was necessary. The interview version was designed to allow administration in both face-to-face interview and telephone interview mode. METHODS: Three members of the research team translated the formal written Chinese in the self-administered version of the WHOQOL-BREF(HK) into colloquial Cantonese separately. Brief notes extracted from the facet definitions of the WHOQOL-100 were added in brackets after some questions to further explain the intention of the questions. Two series of focus groups were conducted and subsequently the field test version was produced. 329 subjects were recruited by convenient sampling method for the field test. RESULTS: The interview version and the self-administered version was found equivalent. The ICC values of the domain scores ranged from 0.73 in the environment domain to 0.83 in the psychological domain. The face-to-face interview and telephone interview mode of administration were also found equivalent. The ICC for the domain scores ranged from 0.76 in the social interaction domain to 0.84 in the psychological domain. The other psychometric properties of the interview version were found comparable to the self-administered version. CONCLUSION: The self-administered and the interview version of the WHOQOL-BREF are regarded as identical in group comparison. The authors advise that it is acceptable to use different versions on different subjects in the same study, provided that the same version is applied on the same subject throughout the study.