Computer Aided Statistical Analysis of Motive Use and Compositional Idiom

This thesis discusses the creation of a means of pitch-based data representation which allows automated logging and analysis of melodic motivic material. This system also allows analysis of a number of attributes of a composition which are not readily apparent to human analysis. By using a numerical data format which treats motivically related material as equivalent, groups of tonally equivalent intervals (n-tuples) can be logged and have statistical procedures carried out on them. This thesis looks at four applications of this approach: measuring the most commonly occurring motivic material; creating a transition matrix showing probabilities of movement between intervals; measuring the extent of disjunct or conjunct writing; and measuring concentration of motivic writing (the extent to which motives are reused). Following the discussion of the data representation system, a set of expositions taken from the piano sonatas of Haydn, Mozart, and Clementi are converted to this method of data representation, and results are collected for the above four applications. The implications of the results of this analysis are discussed, and further potential applications of the system are explored

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

Cost-analysis of treatment of childhood acute lymphoblastic leukemia with asparaginase preparations: The impact of expensive chemotherapy

__Abstract__ Asparaginase is an expensive drug, but important in childhood acute lymphoblastic leukemia. In order to compare costs of PEGasparaginase, Erwinia asparaginase and native E. coli asparaginase, we performed a cost-analysis in the Dutch Childhood Oncology Group ALL-10 medium-risk group intensification protocol. Treatment costs were calculated based on patient level data of 84 subjects, and were related to the occurrence of allergy to PEGasparaginase. Simultaneously, decision tree and sensitivity analyses were conducted. The total costs of the intensification course of 30 weeks were $57,893 in patients without PEGasparaginase allergy (n=64). The costs were significantly higher ($113,558) in case of allergy (n=20) necessitating a switch to Erwinia asparaginase. Simulated scenarios (decision tree analysis) using native E. coli asparaginase in intensification showed that the costs of PEGasparaginase were equal to those of native E. coli asparaginase. Also after sensitivity analyses, the costs for PEGasparaginase were equal to those of na

Psychosocial function of Dutch children with cancer and their caregivers during different phases of the COVID-19 pandemic

We compared psychosocial functioning of children with cancer and their caregivers in several phases of the coronavirus disease 2019 (COVID-19) pandemic to before COVID-19. One or more questionnaires on health-related quality of life (HRQoL) or fatigue of children or distress of their caregivers was available from 1644 families. In children with cancer, HRQoL was stable throughout the COVID-19 pandemic. Fatigue was slightly lower and sleep somewhat better during the pandemic than before. Caregiver distress was lower in the first pandemic phase, but increased to pre-COVID-19 levels in later phases, indicating that the length and consequences of the pandemic may be weighing on them

The impact of maintenance therapy on sleep-wake rhythms and cancer-related fatigue in pediatric acute lymphoblastic leukemia

Purpose: To assess the impact of maintenance therapy and the additional impact of dexamethasone treatment on cancer-related fatigue and sleep-wake rhythms in pediatric acute lymphoblastic leukemia (ALL) patients and to determine the association between these outcomes. Methods: A national cohort of pediatric ALL patients (≥ 2 years) was included (± 1 year post-diagnosis). Patients receiving dexamethasone were assessed twice (assessment with and without dexamethasone). Actigraphy assessments were used to calculate sleep-wake outcomes with nonparametric methods. Cancer-related fatigue was assessed with the PedsQL Multidimensional Fatigue Scale. Sleep-wake rhythms and cancer-related fatigue were compared between patients participating in the assessment without dexamethasone and healthy children (linear regression) and between assessments with and without dexamethasone (mixed models). Using linear regression, associations between sleep-wake outcomes and cancer-related fatigue were determined during assessments with and without dexamethasone. Results: Responses were collected for 125 patients (113 assessments with and 81 without dexamethasone). The sleep-wake rhythm was less stable (p = 0.03) and less robust (p = 0.01), with lower physical activity l

High prevalence of parent-reported sleep problems in pediatric patients with acute lymphoblastic leukemia after induction therapy

Contains fulltext : 219851.pdf (Publisher’s version ) (Open Access)OBJECTIVE: To assess sleep problems (prevalence and predictors) in pediatric patients with acute lymphoblastic leukemia (ALL) after the most intensive phase of therapy (induction). METHODS: Patients (>/=2 years) treated according to the Dutch ALL-11 protocol were included. Sleep was measured using parent-reports and self-reports (Children's Sleep Habits Questionnaire; CSHQ) and actigraphy. Parental sleep (Medical Outcome Study Sleep Scale) and distress and parenting problems (Distress Thermometer for Parents) were assessed with questionnaires. Z-scores were calculated for total CSHQ scores using age-appropriate scores of healthy Dutch children. The prevalence of sleep problems (defined as a Z-score > 1) in patients with ALL was compared to healthy children (chi-square tests). Actigraphic sleep estimates were collected in healthy Dutch children (n = 86, 2-18 years) for comparison with patients (linear regression). Determinants of parent-reported child sleep (total CSHQ Z-score) were identified with regression models. RESULTS: Responses were collected for 124 patients (response rate 67%), comprising 123 parent-reports, 34 self-reports, and 69 actigraphy assessments. Parents reported sleep problems in 38.0% of the patients compared to 15.2% in healthy children (P < .001). Patients reported fewer sleep problems themselves: 12.1% compared to 15.8% in healthy children (P = .33). Total time in bed (B (95% CI): 22.89 (9.55-36.22)) and total sleep time (B (95% CI):16.30 (1.40-31.19)), as derived from actigraphy, were significantly longer in patients. More parent-reported child sleep problems were predicted by parenting problems, more parental sleep problems, bedroom sharing, and child's sleep medication use (explained variance: 27.4%). CONCLUSIONS: Systematic monitoring of child and parental sleep and implementation of effective interventions may be a gateway to improve quality of survival in pediatric ALL.01 april 202

Causes of early death and treatment-related death in newly diagnosed pediatric acute myeloid leukemia:Recent experiences of the Dutch Childhood Oncology Group

Background: With the current more effective treatment regimens for pediatric acute myeloid leukemia (AML), research on early death (ED), treatment-related mortality (TRM), and toxicity becomes increasingly important. The aim of this study was to give an overview of the frequency, clinical features, and risk factors associated with ED and TRM in first complete remission (CR1) during the last three consecutive treatment protocols of the Dutch Childhood Oncology Group (DCOG) between 1998 and 2014. Methods: Incidence and risk factors associated with ED and TRM in CR1 were retrospectively studied in 245 patients treated according to the Dutch ANLL-97/AML-12 (n = 118), AML-15 (n = 60), or DB AML-01 (n = 67) protocols. Results: The incidence of ED was, respectively, 5.1%, 6.7%, and 3.0% excluding deaths before treatment (P = NS), and 7.4%, 11.1%, and 4.4% including deaths before the onset of treatment. Severe underweight at initial diagnosis was significantly associated with more frequent ED. When relapse was included as a competing risk, cumulative incidence of death in CR1 were 5.9%, 5.0%, and 4.6% for ANLL97, AML15, and DB01, respectively (P = NS). The most important cause of TRM included infectious and SCT-related complications. Conclusion: We report relatively stable rates of ED and TRM in CR1 in the latest completed DCOG protocols for newly diagnosed AML patients. The most important causes of TRM were SCT- or infection-related, warranting further evaluation and awareness

Sleep-wake rhythm disruption is associated with cancer-related fatigue in pediatric acute lymphoblastic leukemia

Contains fulltext : 220835.pdf (Publisher’s version ) (Open Access)STUDY OBJECTIVES: To compare sleep-wake rhythms, melatonin, and cancer-related fatigue in pediatric patients with acute lymphoblastic leukemia (ALL) to healthy children and to assess the association between sleep-wake outcomes and cancer-related fatigue. METHODS: A national cohort of ALL patients (2-18 years) was included. Sleep-wake rhythms were measured using actigraphy and generated the following variables: Interdaily stability (IS): higher IS reflects higher stability; intradaily variability (IV): lower IV indicates less fragmentation; L5 and M10 counts: activity counts during the five least and 10 most active hours, respectively; and relative amplitude (RA): the ratio of L5 and M10 counts (higher RA reflects a more robust rhythm). The melatonin metabolite, 6-sulfatoxymelatonin (aMT6s), was assessed in urine. Cancer-related fatigue was assessed with the PedsQL Multidimensional Fatigue Scale. Using regression models sleep-wake rhythms, aMT6s, and cancer-related fatigue were compared to healthy children and associations between sleep-wake outcomes and cancer-related fatigue were assessed in ALL patients. RESULTS: In total, 126 patients participated (response rate: 67%). IS, RA, and M10 counts were lower in patients compared to healthy children (p < 0.001). aMT6s levels were comparable to healthy children (p = 0.425). Patients with ALL were more fatigued compared to healthy children (p < 0.001). Lower IS, RA and M10 counts and higher IV were significantly associated with more parent-reported cancer-related fatigue. Associations between sleep-wake rhythms and self-reported cancer-related fatigue were not statistically significant. CONCLUSIONS: Sleep-wake rhythm impairment is associated with more cancer-related fatigue in pediatric ALL patients. Interventions aimed to improve sleep hygiene and encourage physical activity may reduce cancer-related fatigue

Health-related quality of life and its determinants during and after treatment for paediatric acute lymphoblastic leukaemia:a national, prospective, longitudinal study in the Netherlands

OBJECTIVES: Health-related quality of life (HRQoL) is impaired in paediatric patients with acute lymphoblastic leukaemia (ALL). Over the past decades, ALL treatment has successfully been adjusted to the risk of relapse, which is now reflected by the stratification of patients into three risk groups who receive treatment of differing intensities. This study is the first to evaluate the longitudinal course of HRQoL in light of these adjustments and identify determinants of HRQoL. DESIGN: Two prospective, national cohort studies (add-on studies within the two most recent treatment protocols for children with ALL (ALL-10 and ALL-11)). SETTING: Dutch paediatric oncology hospitals between October 2006 and October 2009 (ALL-10) and between August 2013 and July 2017 (ALL-11).PARTICIPANTS: Patients with ALL (2-18 years) are treated according to the ALL-10 or ALL-11 treatment protocol. Patients treated according to the ALL-10 protocol only completed a cancer-specific QoL measure and patients treated according to the ALL-11 protocol completed both a cancer-specific and generic QoL measure (see below). OUTCOME MEASURES: HRQoL, assessed with parent-proxy questionnaires (PedsQL Generic and Cancer module) within the first 5 months (T0), at 1 year (T1), 2 years (T2) and 3 years (T3) after diagnosis. The proportion of patients with clinically relevant generic HRQoL impairment was compared with healthy norm values. Multivariable mixed model analyses were used to evaluate the development of HRQoL over time and its medical and sociodemographic determinants (collected on enrolment). RESULTS: Of the ALL-10 cohort, 132 families participated and of the ALL-11 cohort, 136 families participated (268 total). Thus, cancer-specific HRQoL assessments were available for 268 patients (median age 5.3 years (IQR 6.15), 56.0% boys, 69.0% medium-risk ALL), and generic HRQoL assessments for 136 patients (median age 4.8 years (IQR 6.13), 60.3% boys, 75.0% medium-risk ALL). Generic HRQoL improved between timepoints T0 and T3 (total score B 16.1, 95% CI 12.2 to 20.1, p&lt;0.001), but did not restore to normal 1 year after the end of treatment: 28.0% of children remained impaired compared with 16% in the general population (p=0.003). Cancer-specific HRQoL generally improved from T0 to T2 (Pain B 11.3, 95% CI 7.1 to 15.5; Nausea B 11.7, 8.4 to 15.1; Procedural Anxiety B 19.1, 14.8 to 23.4; Treatment Anxiety B 12.8, 9.5 to 16.0; Worry B 3.5, 0.6 to 6.3; Communication B 8.5, 5.0 to 11.9; all p&lt;0.001 except for Worry (p=0.02)), while Physical Appearance and Cognitive Functioning remained stable. Higher treatment intensity and experiencing pain or simultaneous chronic illness were associated with lower HRQoL over time for multiple subscales. CONCLUSIONS: HRQoL impairment is prevalent during and after ALL treatment. Patients with standard-risk ALL and reduced treatment intensity have better HRQoL than patients in higher risk groups. Systematic monitoring of HRQoL is of utmost importance in order to provide timely psychosocial interventions and supportive care.</p

Insomnia Symptoms and Daytime Fatigue Co-Occurrence in Adolescent and Young Adult Childhood Cancer Patients in Follow-Up after Treatment:Prevalence and Associated Risk Factors

Simple Summary Insomnia symptoms and daytime fatigue significantly impact physical and psychosocial health. While these are common symptoms in pediatric oncology, relationships between these symptoms remain unclear. This study evaluated the prevalence of insomnia only, daytime fatigue only, the co-occurrence of insomnia and daytime fatigue symptoms, and associated risk factors in adolescent/young adult childhood cancer patients in follow-up after treatment. Results showed that around forty percent had insomnia and daytime fatigue symptoms, which often co-occurred. Risk factors that emerged were: female sex and co-morbidities (all), shorter time after treatment and bedtime gaming (insomnia only), young adulthood (insomnia-fatigue and fatigue only), needing someone else to fall asleep and inconsistent wake times (both insomnia groups), and lower educational level and consistent bedtimes (insomnia-fatigue). Overall, insomnia symptoms and daytime fatigue were common and often co-occurred in this patient population. While current fatigue guidelines do not include insomnia symptoms, healthcare providers should inquire about insomnia as this potentially provides additional options for treatment and prevention. Insomnia symptoms and daytime fatigue commonly occur in pediatric oncology, which significantly impact physical and psychosocial health. This study evaluated the prevalence of insomnia only, daytime fatigue only, the co-occurrence of insomnia-daytime fatigue symptoms, and associated risk factors. Childhood cancer patients (n = 565, 12-26 years old, >= 6 months after treatment) participated in a national, cross-sectional questionnaire study, measuring insomnia symptoms (ISI; Insomnia Severity Index) and daytime fatigue (single item). Prevalence rates of insomnia and/or daytime fatigue subgroups and ISI severity ranges were calculated. Multinomial regression models were applied to assess risk factors. Most patients reported no insomnia symptoms or daytime fatigue (61.8%). In the 38.2% of patients who had symptoms, 48.1% reported insomnia and daytime fatigue, 34.7% insomnia only, and 17.1% daytime fatigue only. Insomnia scores were higher in patients with insomnia-daytime fatigue compared to insomnia only (p < 0.001). Risk factors that emerged were: female sex and co-morbidities (all), shorter time after treatment and bedtime gaming (insomnia only), young adulthood (insomnia-fatigue/fatigue only), needing someone else to fall asleep and inconsistent wake times (both insomnia groups), lower educational level and consistent bedtimes (insomnia-fatigue). Insomnia symptoms and daytime fatigue are common and often co-occur. While current fatigue guidelines do not include insomnia symptoms, healthcare providers should inquire about insomnia as this potentially provides additional options for treatment and prevention