Individual Factors Contributing to Nausea in First-Time Chemotherapy Patients: A Prospective Cohort Study

Objective: The expectation of developing side effects can enhance the likelihood to develop them – a phenomenon referred to as nocebo effect. Whether nocebo effects can be reduced by lowering negative expectancies, is not clear. The aim of this prospective study was to learn more about the factors contributing to nausea expectancy and their potential role in actual occurrence of nausea in patients undergoing chemotherapy for the first time in their life. Methods: Patients scheduled for moderately emetogenic chemotherapeutic regimens filled in questionnaires to assess state anxiety and quality of life and to rate the expectancy of nausea as a side effect of chemotherapy. Patient diaries were used to monitor the severity of post-chemotherapy nausea in the 4 days following chemotherapy administration. Bivariate analyses complemented by multiple regression analyses were performed to identify the relationship between nausea expectation and nausea occurrence. Results: 121 female patients (mean age 53 years) with completed questionnaires were included in the analyses. The majority of the patients had a diagnosis of breast cancer (86%). The two main sources for nausea expectancy were positive history of nausea in other situations and state anxiety. Patients with high expectancy levels (first quartile) experienced greater nausea than those with lower expectancy levels. Bivariate analyses revealed a weak but non-significant association between nausea expectation and post-chemotherapy nausea. When controlling for age, type of cancer, history of nausea, state and trait anxiety, and global quality of life, positive history of nausea (OR = 2.592; 95% CI, 1.0 to 6.67; p < 0.05), younger age (OR = 0.95; 95% CI, 0.92 to 0.99; p < 0.05), and a lower quality of life (OR = 0.97; 95% CI, 0.94 to 1.0; p < 0.05), but not nausea expectancy (OR = 1.014; 95% CI, 0.51 to 2.02; p = 0.969), predicted the occurrence of post-chemotherapy nausea. Conclusion: In this female cohort, younger patients with lower initial quality of life and a positive history of nausea were at higher risk to develop nausea after first time chemotherapy. These patients may benefit from psychological co-interventions that aim to enhance quality of life

Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells - TREAT-ME-1-a phase I, first in human, first in class trial

Purpose: This phase I, first in human, first in class clinical study aimed at evaluating the safety, tolerability and efficacy of treatment with genetically modified mesenchymal stromal cells (MSC) in combination with ganciclovir (GCV). MSC_apceth_ 101 are genetically modified autologous MSCs used as vehicles for a cell-based gene therapy in patients with advanced gastrointestinal adenocarcinoma. Experimental design: The study design consisted of a dose-escalation 3 + 3 design. All patients (n = 6) were treated with up to three applications of MSC_apceth_101, followed by GCV infusions given on three consecutive days starting 48 hours after injection of MSC_apceth_101. Three of six patients received a total dose of 1.5 x 10(6) cells/kg. Two patients received three doses of 1 x 10(6) cells/kg, while one patient received only two doses of 1 x 10(6) cells/kg due to a SADR. Results: Six patients received MSC_apceth_101. No IMP-related serious adverse events occurred. Adverse-events related to IMP-injection were increased creatinine, cough, fever, and night sweat. TNF, IL-6, IL-8, IL-10 and sE-Selectin, showed that repeated application is immunologically safe, but induces a switch of the functional properties of monocytes to an inflammatory phenotype. Treatment induced stable disease in 4/6 patients, and progressive disease in 2/6 patients. Conclusion: Treatment with MSC_ apceth_101 in combination with GCV demonstrated acceptable safety and tolerability in patients with advanced gastrointestinal adenocarcinoma

Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells: Results from the phase 1/2 TREAT-ME-1 trial

TREAT-ME-1, a Phase 1/2 open-label multicenter, first-in-human, first-in-class trial, evaluated the safety, tolerability and efficacy of treatment with genetically modified autologous mesenchymal stromal cells (MSC), MSC_ apceth_101, in combination with ganciclovir in patients with advanced gastrointestinal adenocarcinoma. Immunological and inflammatory markers were also assessed. All patients (3 in Phase 1; 7 in Phase 2) received three treatment cycles of MSC_apceth_101 at one dose level on Day 0, 7, and 14 followed by ganciclovir administration according to the manufacturer's instructions for 4872 h after MSC_apceth_101 injection. Ten patients were treated with a total dose of 3.0 x 10(6) cells/kg MSC_apceth_101. 36 adverse events and six serious adverse events were reported. Five patients achieved stable disease (change in target lesions of -2 to +28%). For all patients, the median time to progression was 1.8 months (95% CI: 0.5, 3.9 months). Median overall survival could not be estimated as 8/10 patients were still alive at the end of the study (1 year) and therefore censored. Post-study observation of patients showed a median overall survival of 15.6 months (ranging from 2.227.0 months). Treatment with MSC_apceth_101 and ganciclovir did not induce a consistent increase or decrease in levels of any of the tumor markers analyzed. No clear trends in the immunological markers assessed were observed. MSC_apceth_101 in combination with ganciclovir was safe and tolerable in patients with advanced gastrointestinal adenocarcinoma, with preliminary signs of efficacy in terms of clinical stabilization of disease

Prevalence, associated factors and predictors of depression among adults in the community of Selangor, Malaysia

Introduction Depression is one of the most common mental health disorders and is an emerging public health problem. The objectives of this paper were to determine the prevalence of depression, its associated factors and the predictors of depression among adults in the community of Selangor. Methods A cross sectional study was conducted in three districts in Selangor, from 11th June to 30th December 2012. The sampling frame was obtained from the Department of Statistics Malaysia (DOS) in May 2012, using the National Population and Housing Census 2010. Adults aged 18 years and above, living in the selected living quarters were approached to participate in the study and requested to complete a set of questionnaires. Results A total of 1,556 out of 2,152 participants participated in this study, giving an overall study response rate of 61.90%. Patient Health Questionnaire 9 (PHQ-9) was used to determine the presence of depression. The prevalence of depression was 10.3%, based on the PHQ-9 cut off point of 10 and above. Based on multiple logistic regression analysis, the predictors of depression were presence of anxiety, serious problems at work, unhappy relationship with children, high perceived stress, domestic violence, unhappy relationship with spouse, low self-esteem, unhappy relationship with family, serious financial constraint and presence of chronic diseases. When reanalyzed after removing anxiety, high perceived stress and low self-esteem, additional predictors of depression were found to be serious marital problems and religiosity. Conclusion The prevalence of depression in this study is similar to that found in other studies. Findings from this study are being used as baseline data to develop an effective program to assist in the management of common mental health disorders in the community, in particular depression. The identification of predictors of depression in the community is important to identify the target population for the program