Online focus groups as a tool to collect data in hard-to-include populations: examples from paediatric oncology

Contains fulltext : 81501.pdf (publisher's version ) (Open Access)BACKGROUND: The purpose of this article is to describe and evaluate the methodology of online focus group discussions within the setting of paediatric oncology. METHODS: Qualitative study consisting of separate moderated asynchronous online discussion groups with 7 paediatric cancer patients (aged 8-17), 11 parents, and 18 survivors of childhood cancer (aged 8-17 at diagnosis). RESULTS: All three participant groups could be actively engaged over a one-week period. Respondents highly valued the flexibility and convenience of logging in at their own time and place to join the discussion. Adolescent patients and survivors emphasized that the anonymity experienced made them feel comfortable to express their views in detail. The findings indicate a strong preference for online group discussions across all participant groups. CONCLUSION: The findings show that online focus group methodology is a feasible tool for collecting qualitative data within the setting of paediatric oncology, and may offer new opportunities to collect data in other hard-to-include populations. The evaluations seem to indicate that the online group discussions have given participants an opportunity to articulate their experiences and views in a way they might not have done in a traditional group discussion.9 p

Impaired sleep affects quality of life in children during maintenance treatment for acute lymphoblastic leukemia: an exploratory study

Contains fulltext : 97021.pdf (publisher's version ) (Open Access)BACKGROUND: With the increase of pediatric cancer survival rates, late effects and quality of life (QoL) have received more attention. Disturbed sleep in pediatric cancer is a common clinical observation, but research on this subject is sparse. In general, sleep problems can lead to significant morbidity and are associated with impaired QoL. Information on sleep is essential to develop interventions to improve QoL. METHODS: Children (2-18 years) with acute lymphoblastic leukemia (ALL) were eligible for this multi-center study. The Children's Sleep Habits Questionnaire (CSHQ), Child Health Questionnaire (CHQ) and Pediatric Quality of Life Inventory 3.0 Acute Cancer Version (PedsQL) were used to assess sleep and QoL halfway through maintenance therapy. Sleep and QoL were measured during and after dexamethasone treatment (on-dex and off-dex). RESULTS: Seventeen children participated (age 6.7 +/- 3.3 years, 44% boys). Children with ALL had more sleep problems and a lower QoL compared to the norm. There were no differences on-dex and off-dex. Pain (r = -0.6; p = 0.029) and worry (r = -0.5; p = 0.034) showed a moderate negative association with sleep. Reduced overall QoL was moderately associated with impaired overall sleep (r = -0.6; p = 0.014) and more problems with sleep anxiety (r = -0.8; p = 0.003), sleep onset delay (r = -0.5; p = 0.037), daytime sleepiness (r = -0.5; p = 0.044) and night wakenings (r = -0.6; p = 0.017). CONCLUSION: QoL is impaired in children during cancer treatment. The results of this study suggest that impaired sleep may be a contributing determinant. Consequently, enhanced counseling and treatment of sleep problems might improve QoL. It is important to conduct more extensive studies to confirm these findings and provide more detailed information on the relationship between sleep and QoL, and on factors affecting sleep in pediatric ALL and in children with cancer in general

Predicting trajectories of behavioral adjustment in children diagnosed with acute lymphoblastic leukemia

Purpose Previous research showed that children with cancer are at risk for developing behavioral adjustment problems after successful treatment; however, the course of adjustment remains unclear. This study focuses on adjustment trajectories of children during treatment for acute lymphoblastic leukemia (ALL) and aims to distinguish subgroups of patients showing different trajectories during active treatment, and to identify sociodemographic, medical, and psychosocial predictors of the distinct adjustment trajectories. Methods In a multicenter longitudinal study, 108 parents of a child (response rate 80 %) diagnosed with ALL were assessed during induction treatment (T0), after induction/consolidation treatment (T1), and after end of treatment (T2). Trajectories of child behavioral adjustment (Child Behavior Checklist; CBCL) were tested with latent class growth modeling (LCGM) analyses. Results For internalizing behavior, a three-trajectory model was found: a group that experienced no problems (60 %), a group that experienced only initial problems (30 %), and a group that experienced chronic problems (10 %). For externalizing behavior, a three-trajectory model was also found: a group that experienced no problems (83 %), a group that experienced chronic problems (12 %), and a group that experienced increasing problems (5 %). Only parenting stress and baseline QoL (cancer related) were found to contribute uniquely to adjustment trajectories. Conclusions The majority of the children (77 %) showed no or transient behavioral problems during the entire treatment as reported by parents. A substantial group (23 %) shows maladaptive trajectories of internalizing behavioral problems and/or externalizing behavioral problems. Screening for risk factors for developing problems might be helpful in early identification of these children

Cost-effectiveness of Anti-CD19 chimeric antigen receptor T-Cell therapy in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia. A societal view

Introduction: In several studies, the chimeric antigen receptor T-cell therapy tisagenlecleucel demonstrated encouraging rates of remission and lasting survival benefits in pediatric patients with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL). We assessed the cost-effectiveness of tisagenlecleucel (list price: 320 000 EUR) among these patients when compared to clofarabine monotherapy (Clo-M), clofarabine combination therapy (Clo-C), and blinatumomab (Blina) from both a healthcare and a societal perspective. We also assessed future medical and future non-medical consumption costs. Methods: A three-state partitioned survival model was used to simulate a cohort of pediatric patients (12 years of age) through different disease states until the end of life (lifetime horizon). Relevant outcomes were life years, quality-adjusted life years (QALYs), healthcare costs, societal costs, and the incremental cost-effectiveness ratio (ICER). Uncertainty was explored through deterministic and probabilistic sensitivity analyses as well as through several scenario analyzes. Results: Total discounted costs for tisagenlecleucel were 552 679 EUR from a societal perspective, which was much higher than the total discounted costs from a healthcare perspective (ie, 409 563 EUR). Total discounted societal costs for the comparator regimens ranged between 160 803 EUR for Clo-M and 267 259 EUR for Blina. Highest QALYs were estimated for tisagenlecleucel (11.26), followed by Blina (2.25), Clo-C (1.70) and Clo-M (0.74). Discounted societal ICERs of tisagenlecleucel ranged between 31 682 EUR/QALY for Blina and 37 531 EUR/QALY for Clo-C and were considered cost-effective with a willingness-to-pay (WTP) threshold of 80 000 EUR/QALY. None of the scenarios exceeded this threshold, and more than 98% of the iterations in the probabilistic sensitivity analysis were cost-effective. Discussion: At the current price and WTP threshold, tisagenlecleucel is cost-effective from both a healthcare and a societal perspective. Nevertheless, long-term effectiveness data are needed to validate the several assumptions that were necessary for this model

Computer simulations of domain growth and phase separation in two-dimensional binary immiscible fluids using dissipative particle dynamics

We investigate the dynamical behavior of binary fluid systems in two dimensions using dissipative particle dynamics. We find that following a symmetric quench the domain size R(t) grows with time t according to two distinct algebraic laws R(t) = t^n: at early times n = 1/2, while for later times n = 2/3. Following an asymmetric quench we observe only n = 1/2, and if momentum conservation is violated we see n = 1/3 at early times. Bubble simulations confirm the existence of a finite surface tension and the validity of Laplace's law. Our results are compared with similar simulations which have been performed previously using molecular dynamics, lattice-gas and lattice-Boltzmann automata, and Langevin dynamics. We conclude that dissipative particle dynamics is a promising method for simulating fluid properties in such systems.Comment: RevTeX; 22 pages, 5 low-resolution figures. For full-resolution figures, connect to http://www.tcm.phy.cam.ac.uk/~ken21/tension/tension.htm

Influence of Genetic Variants in TPMT and COMT Associated with Cisplatin Induced Hearing Loss in Patients with Cancer:Two New Cohorts and a Meta-Analysis Reveal Significant Heterogeneity between Cohorts

Treatment with cisplatin-containing chemotherapy regimens causes hearing loss in 40-60% of cancer patients. It has been suggested that genetic variants in the genes encoding thiopurine S-methyltransferase (TPMT) and catechol O-methyltransferase (COMT) can predict the development of cisplatin-induced ototoxicity and may explain interindividual variability in sensitivity to cisplatin-induced hearing loss. Two recently published studies however, sought to validate these findings and showed inconsistent results. The aim of this study was to evaluate the role of polymorphisms in the TPMT and COMT genes in cisplatin-induced ototoxicity. Therefore we investigated two independent cohorts of 110 Dutch and 38 Spanish patients with osteosarcoma and performed a meta-analysis including all previously published studies resulting in a total population of 664 patients with cancer. With this largest meta-analysis performed to date, we show that the influence of TPMT and COMT on the development of cisplatin-induced hearing loss may be less important than previously suggested

Functional analysis of novel androgen receptor mutations in a unique cohort of Indonesian patients with a disorder of sex development

Mutations in the androgen receptor (AR) gene, rendering the AR protein partially or completely inactive, cause androgen insensitivity syndrome, which is a form of a 46,XY disorder of sex development (DSD). We present 3 novel AR variants found in a cohort of Indonesian DSD patients: p.I603N, p.P671S, and p.Q738R. The aim of this study was to determine the possible pathogenic nature of these newly found unclassified variants. To investigate the effect of these variants on AR function, we studied their impact on transcription activation, AR ligand-binding domain interaction with an FxxLF motif containing peptide, AR subcellular localization, and AR nuclear dynamics and DNA-binding. AR-I603N had completely lost its transcriptional activity due to disturbed DNA-binding capacity and did not show the 114-kDa hyperphosphorylated AR protein band normally detectable after hormone binding. The patient with AR-I603N displays a partial androgen insensitivity syndrome phenotype, which is explained by somatic mosaicism. A strongly reduced transcriptional activity was observed for AR-Q738R, together with diminished interaction with an FxxLF motif containing peptide. AR-P671S also showed reduced transactivation ability, but no change in DNA- or FxxLF-binding capacity and interferes with transcriptional activity for as yet unclear reasons

Aggravated bone density decline following symptomatic osteonecrosis in children with acute lymphoblastic leukemia

Osteonecrosis and decline of bone density are serious side effects during and after treatment of childhood acute lymphoblastic leukemia. It is unknown whether osteonecrosis and low bone density occur together in the same patients, or whether these two osteogenic side-effects can mutually influence each other's development. Bone density and the incidence of symptomatic osteonecrosis were prospectively assessed in a national cohort of 466 patients with acute lymphoblastic leukemia (4-18 years of age) who were treated according to the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Bone mineral density of the lumbar spine (BMDLS) (n= 466) and of the total body (BMDTB) (n=106) was measured by dual X-ray absorptiometry. Bone density was expressed as age-and gender-matched standard deviation scores. Thirty patients (6.4%) suffered from symptomatic osteonecrosis. At baseline, BMDLS and BMDTB did not differ between patients who did or did not develop osteonecrosis. At cessation of treatment, patients with osteonecrosis had lower mean BMDLS and BMDTB than patients without osteonecrosis (respectively, with osteonecrosis: -2.16 versus without osteonecrosis: -1.21, P</p