RESUMEN
OBJECTIVES: The vast majority of children with Attention-Deficit Hyperactivity Disorder (ADHD) do not have access to proper diagnosis and treatment in China. The goal of this project is to identify the challenges and facilitators in implementing a Canadian ADHD Shared Care Pathways program in pediatric settings in Shanghai region. METHODS: Purposive semi-structured focus groups were conducted on a total of 13 healthcare practitioners from the Shanghai Xinuha, Ninghai and Chongming hospitals. Two independent researchers conducted a thematic analysis of the data with themes emerging based on the Consolidated Framework for Implementation Research (CFIR). RESULTS: Notable barriers identified by participants included: (1) lack of knowledge in the management of ADHD, primarily among general practitioners; (2) lack of resources such as lack of staff, time, and medication for ADHD; (3) challenges in implementing an international multicentre intervention (such as communication difficulties between teams and integration of resources available in different hospitals); and (4) mental health stigma, difficulties in identifying ADHD patients, and logistical problems related to medication procurement rules put in place by provincial governments. Notable facilitators included: (1) the strong motivation of stakeholders and their confidence in their ability to learn and subsequently execute action plans to achieve the implementation goal; (2) the compatibility between the values and goals of the stakeholders and those of the program despite some cultural tension, a positive learning climate, strong tensions for change, and the high interest of organization leaders in engaging in the program (3) the perceived benefits of the program, such as standardization of the diagnostic and treatment process, and engaging primary care providers in ADHD management; and (4) the strong relationship between participating institutions and schools as well as provincial health initiatives available to support collaborative models of care. Mixed factors to implementation were also explored. CONCLUSIONS: Appropriate training of health care providers, cultural adaptation of the program, increase public awareness about ADHD to decrease stigma, as well as strong project management and guidelines that clearly describe the role and expectations of each team member appeared essential to successful implementation.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Grupos Focales , Humanos , Trastorno por Déficit de Atención con Hiperactividad/terapia , China , Canadá , Niño , Masculino , Femenino , Accesibilidad a los Servicios de Salud , Investigación Cualitativa , Actitud del Personal de SaludRESUMEN
Methylphenidate (MPH) is a psychostimulant which inhibits the uptake of dopamine and norepinephrine transporters, DAT and NET, and is mostly used to treat Attention Deficit/Hyperactivity Disorder. The current dose optimization is done through titration, a cumbersome approach for patients. To assess the therapeutic performance of MPH regimens, we introduce an in silico framework composed of (i) a population pharmacokinetic model of MPH, (ii) a pharmacodynamic (PD) model of DAT and NET occupancy, (iii) a therapeutic box delimited by time and DAT occupancy, and (iv) a performance score computation. DAT occupancy data was digitized (n = 152) and described with Emax models. NET occupancy was described with a KPD model. We used this integrative framework to simulate the performance of extended-release (18-99 mg) and tid MPH regimens (25-40 mg). Early blood samples of MPH seem to lead to higher DAT occupancy, consistent with an acute tolerance observed in clinical rating scales. An Emax model with a time-dependent tolerance was fitted to available data to assess the observed clockwise hysteresis. Peak performance is observed at 63 mg. While our analysis does not deny the existence of an acute tolerance, data precision in terms of formulation and sampling times does not allow a definite confirmation of this phenomenon. This work justifies the need for a more systematic collection of DAT and NET occupancy data to further investigate the presence of acute tolerance and assess the impact of low MPH doses on its efficacy.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Metilfenidato , Humanos , Metilfenidato/farmacología , Metilfenidato/uso terapéutico , Dopamina , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática , Estimulantes del Sistema Nervioso Central/farmacocinética , Estimulantes del Sistema Nervioso Central/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológicoRESUMEN
Late effects such as neurocognitive issues and fatigue have been reported in childhood acute lymphoblastic leukemia (cALL) survivors. Yet, their association is often poorly understood. In this study, we wished to (1) describe neurocognitive difficulties and fatigue in a well-characterized cohort of long-term cALL survivors and (2) explore the risk of having neurocognitive deficits as a function of fatigue. Childhood ALL survivors (N = 285) from three Canadian treatment centers completed the DIVERGT battery of cognitive tests and the PedsQL Multidimensional Fatigue Scale. We performed logistic regressions to assess the risk of a survivor to show cognitive deficits (<2.0 SD) depending on their fatigue levels. At least one cognitive deficit on the DIVERGT was present in 31% of participants. Domains primarily affected were working memory, fine motor skills, and verbal fluency. Sleep/rest fatigue in youths was higher than norms (d = 0.35). The risk for cognitive deficits increased independently with levels of fatigue in the domains of cognitive speed and flexibility, working memory, and verbal fluency. For every 10-point increase on general or sleep/rest fatigue on the 0-100 scale, there was a median +23-35% risk of showing a deficit among the 7 tasks significantly associated with fatigue. Fatigue may constitute a complementary target when searching to mitigate cognitive issues in this population.
Asunto(s)
Disfunción Cognitiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Humanos , Canadá/epidemiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/complicaciones , Sobrevivientes , Fatiga/etiología , Fatiga/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMEN
BACKGROUND: The shared care pathway for ADHD is a program developed in Canada with two main strategies: (a) implement a shared care pathway between general practitioners (GPs) and specialists, and (b) step up or down care so that the patient is treated at the most appropriate level of care, depending on the complexity or outcome of their illness. The current study aims to identify the challenges and facilitators of implementing this program in a Chinese mental health service setting. METHODS: Two focus groups were conducted using semi-structured interviews with a total of 7 health care providers in Beijing. An adapted grounded theory methodology using open-ended, axial and selective coding was used for data analysis. RESULTS: We identified three main levels related to barriers and facilitators: (1) a sociocultural level of patients' and health care providers' perspectives; (2) a structural level related to internal and external organizational environments; (3) and the level of the intervention itself with its characteristics. The project is generally aligned with the mandates and goals of the health system, but two of the main obstacles are the varying qualifications of physicians in hospitals of different levels, implying different needs and flexible and adapted training programs, and the lack of appropriate patient referral systems between the different hospital levels. CONCLUSION: Our study highlights the importance of consultation to obtain a "lay of the land" for deciding on the implementation steps of an a priori well accepted model of care.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno por Déficit de Atención con Hiperactividad/terapia , Beijing , Canadá , Grupos Focales , Personal de Salud , Humanos , Investigación CualitativaRESUMEN
Olfaction contributes to feeding behaviour and is modulated by changes in dopamine levels. Methylphenidate (MPH) increases brain dopamine levels and has been shown to reduce appetite and promote weight loss in patients with attention deficit hyperactivity disorder. The objectives of this study were to test the effect of MPH on olfaction, appetite, energy intake, and body weight (BW) on individuals with obesity. In a randomized, double-blind study, 12 participants (age 28.9 ± 6.7 years) with a body mass index (BMI) of 36.1 ± 4.5 kg/m2 were assigned to MPH (0.5 mg/kg) (n = 5) or placebo (n = 7) twice daily for 2 months. Appetite (visual analog scale), odour threshold (Sniffin' Sticks®), energy intake (food menu), and BW (DEXA scan) were measured at day 1 and day 60. MPH intake significantly increased odour threshold scores (6.3 ± 1.4 vs. 9.4 ± 2.1 and 7.9 ± 2.3 vs. 7.8 ± 1.9, respectively; p = 0.029) versus placebo. There was a significantly greater suppression of appetite sensations (desire to eat (p = 0.001), hunger (p = 0.008), prospective food consumption (p = 0.003)) and an increase in fullness (p = 0.028) over time in the MPH versus placebo. MPH suppressed appetite and improved olfactory sensitivity in individuals with obesity. These data provide novel findings on the favourable effects of MPH on appetite and weight regulation in individuals living with obesity.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Metilfenidato , Adulto , Apetito/fisiología , Dopamina/farmacología , Dopamina/uso terapéutico , Método Doble Ciego , Humanos , Metilfenidato/farmacología , Metilfenidato/uso terapéutico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Olfato , Adulto JovenRESUMEN
BACKGROUND: Childhood cancer survivors should be routinely screened for psychological distress. However, existing screening tools promoted by cancer care institutions, such as the Distress Thermometer (DT) generate high rates of errors. The aim of this study is to help refining strategies of screening psychological distress in this population by exploring two-step methods combining the DT on step #1 with one question on step #2. PROCEDURE: Data from 255 survivors of childhood acute lymphoblastic leukemia aged 13-40 years were analyzed (38% 13-18 years, 62% 19+ years, 53% females). We used the DT on step #1 and the individual emotion items from the Pediatric Quality of Life Questionnaire (PedsQL) on step #2, to detect distress, depression and anxiety as measured by standard instruments. We compared sensitivity, specificity, negative and positive predictive values, Youden index, and clinical utility indices, in newly developed two-step strategies. RESULTS: The best two-step strategies to screen anxious-depressive distress were DT ≥ 2 on step #1, with the item of Sadness on step #2, and DT ≥ 2 combined with the item of Concerns. Two-step strategies outperformed the DT alone on the correct identification of distressed survivors. However, two-step strategies did not outperform the DT used alone on the correct detection of no distressed survivors. Results were similar when predicting depression or anxiety alone. CONCLUSION: Completing the DT with one single question on emotions from the PedsQL may minimize the number of participants falsely identified as distressed, which could be particularly pertinent in resource-limited clinics.
Asunto(s)
Supervivientes de Cáncer , Neoplasias , Ansiedad/psicología , Supervivientes de Cáncer/psicología , Niño , Depresión/psicología , Detección Precoz del Cáncer , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Neoplasias/psicología , Psicometría , Calidad de Vida , Estrés Psicológico/psicología , Encuestas y Cuestionarios , Sobrevivientes/psicologíaRESUMEN
Levodopa is considered the gold standard treatment of Parkinson's disease. Although very effective in alleviating symptoms at their onset, its chronic use with the progressive neuronal denervation in the basal ganglia leads to a decrease in levodopa's effect duration and to the appearance of motor complications. This evolution challenges the establishment of optimal regimens to manage the symptoms as the disease progresses. Based on up-to-date pathophysiological and pharmacological knowledge, we developed an integrative model for Parkinson's disease to evaluate motor function in response to levodopa treatment as the disease progresses. We combined a pharmacokinetic model of levodopa to a model of dopamine's kinetics and a neurocomputational model of basal ganglia. The parameter values were either measured directly or estimated from human and animal data. The concentrations and behaviors predicted by our model were compared to available information and data. Using this model, we were able to predict levodopa plasma concentration, its related dopamine concentration in the brain and the response performance of a motor task for different stages of disease.
Asunto(s)
Ganglios Basales/efectos de los fármacos , Levodopa/farmacocinética , Modelos Neurológicos , Enfermedad de Parkinson/tratamiento farmacológico , Transmisión Sináptica/efectos de los fármacos , Ganglios Basales/metabolismo , Ganglios Basales/fisiopatología , Simulación por Computador , Progresión de la Enfermedad , Dopamina/metabolismo , Humanos , Levodopa/administración & dosificación , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Enfermedad de Parkinson/fisiopatologíaRESUMEN
Previous studies showed that healthy young adults who spontaneously use caudate nucleus-dependent strategies on a virtual navigation task, have significantly lower basal levels of cortisol compared with adults who use hippocampus-dependent spatial navigation strategies. In the current paper, we assessed the relation between basal cortisol levels and learning using a virtual navigation task in children. We show that basal cortisol level has a differential effect on learning and memory between children using spatial and response navigation strategies. Specifically, cortisol was found to be beneficial for learning performance in children using spatial strategies, such that higher levels of cortisol were associated with more efficient learning in a virtual maze. In contrast, cortisol had a deleterious effect on learning the virtual maze in children using response strategies, such that higher cortisol levels were associated with increased spatial working memory errors. Based on these results, individual differences in navigation strategy could help explain contradictory results in the literature showing that cortisol can have either a positive or negative association with learning and memory performance.
Asunto(s)
Hidrocortisona/fisiología , Aprendizaje por Laberinto/fisiología , Memoria Espacial/fisiología , Navegación Espacial/fisiología , Núcleo Caudado/fisiología , Niño , Femenino , Hipocampo/fisiología , Humanos , Masculino , Memoria a Corto Plazo/fisiologíaRESUMEN
OBJECTIVES: The frequency of cognitive difficulties in childhood cancer survivors varies according to the measurement strategy. The goal of this research is to (a) describe agreements and differences between measures of working memory and attention (b) identify contributors of these differences, such as emotional distress, affects, and fatigue. METHODS: We used data available for 138 adults successfully treated for childhood acute lymphoblastic leukemia (ALL) (PETALE cohort). Working memory and attention were assessed using subtests from the WAIS-IV and self-reported questionnaires (BRIEF-SR and CAARS-S:L). Potential contributors included emotional distress, anxiety, depression (BSI-18), affects (PANAS), and fatigue (PedsQL-MFS). We explored measurement agreements and differences using diagnostic indices and multivariate regression models. RESULTS: The frequencies of working memory and attention deficits were higher when using cognitive tests (15%-21%) than with self-reports (10%-11%). Self-reported questionnaires showed high specificity (median 0.87) and low sensitivity (median 0.10), suggesting they did not reliably identify positive cases on cognitive tests. We identified negative affectivity as a possible contributor to inconsistencies between self-report and test results. CONCLUSIONS: When measuring working memory and attention in childhood ALL survivors, cognitive test results and self-reports should not be considered equivalent. At best, self-report may be used for screening (high specificity), but not to assess prevalence in large samples. Self-reported difficulties are also probably influenced by the negative mood in this population.
Asunto(s)
Ansiedad/psicología , Atención/fisiología , Supervivientes de Cáncer/psicología , Disfunción Cognitiva/psicología , Memoria a Corto Plazo/fisiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicología , Adolescente , Adulto , Ansiedad/epidemiología , Canadá/epidemiología , Niño , Disfunción Cognitiva/epidemiología , Estudios de Cohortes , Emociones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , AutoinformeRESUMEN
The effect of levodopa in alleviating the symptoms of Parkinson's disease is altered in a highly nonlinear manner as the disease progresses. This can be attributed to different compensation mechanisms taking place in the basal ganglia where the dopaminergic neurons are progressively lost. This alteration in the effect of levodopa complicates the optimization of a drug regimen. The present work aims at investigating the nonlinear dynamics of Parkinson's disease and its therapy through mechanistic mathematical modeling. Using a holistic approach, a pharmacokinetic model of levodopa was combined to a dopamine dynamics and a neurocomputational model of basal ganglia. The influence of neuronal death on these different mechanisms was also integrated. Using this model, we were able to investigate the nonlinear relationships between the levodopa plasma concentration, the dopamine brain concentration, and a response to a motor task. Variations in dopamine concentrations in the brain for different levodopa doses were also studied. Finally, we investigated the narrowing of a levodopa therapeutic index with the progression of the disease as a result of these nonlinearities. In conclusion, various consequences of nonlinear dynamics in Parkinson's disease treatment were studied by developing an integrative model. This model paves the way toward individualization of a dosing regimen. Using sensor based information, the parameters of the model could be fitted to individual data to propose optimal individual regimens.
Asunto(s)
Levodopa , Enfermedad de Parkinson , Antiparkinsonianos/farmacología , Ganglios Basales , Progresión de la Enfermedad , Humanos , Levodopa/farmacología , Enfermedad de Parkinson/tratamiento farmacológicoRESUMEN
Introduction. Most childhood acute lymphoblastic leukemia (ALL) survivors develop chronic treatment-related adverse effects several years after the end of the treatment. Regular physical activity and a good cardiorespiratory fitness can decrease the risks of neurological disturbances and increase cognitive function scores. The aim of this study was to examine the effect of good cardiorespiratory fitness and physical activity levels on cognitive functions.Methods. We enrolled 219 survivors of childhood ALL. The participants underwent a cardiopulmonary exercise test, neuropsychological tests of executive functions (i.e. verbal fluency, cognitive flexibility, working memory, processing speed) and completed a physical activity questionnaire. We calculated the odds ratio to obtain the preventive fraction of physical activity and cardiorespiratory fitness levels on cognitive functions.Results. The cohort is 52% male and 48% female. A total of 182 survivors (83%) have a cardiorespiratory fitness below their predicted (<100%). Our analyses show that there is an association between good cardiorespiratory fitness and processing speed (preventive fraction of 70% for dominant hand (p < 0.01) and 65% for non-dominant hand (p < 0.01)) and with cognitive flexibility identified as the category switching measure of the D-KEFS verbal fluency (preventive fraction of 61%; p < 0.05).Conclusion. Good cardiorespiratory fitness and good levels of physical activity were associated to a preventive fraction for most cognitive function parameters measured. Good cardiorespiratory fitness levels were significantly associated with a lower prevalence of deficits in processing speed (i.e., dominant hand and non-dominant hand) and in cognitive flexibility (i.e., category switching) in childhood acute lymphoblastic leukemia survivors.
Asunto(s)
Supervivientes de Cáncer , Capacidad Cardiovascular , Cognición , Ejercicio Físico , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatología , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Oportunidad Relativa , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Treatments against ALL might lead to later cognitive effects and alterations in brain structure in survivors but to the authors' knowledge the observed variability in the severity of neurocognitive deficits is not fully understood. The objective of the current study was to investigate abnormalities in visual short-term memory (VSTM) brain activation in survivors of childhood ALL using magnetoencephalography. METHODS: A VSTM task was completed by 40 survivors of ALL and 26 controls. VSTM capacity (Cowan K) and brain activation were assessed during the retention period of the task (400-1400 milliseconds) using a standard minimum norm source localization method. RESULTS: Performance (Cowan K) was found to be similar between survivors of ALL and controls. Atypical brain activation was found in survivors of ALL during the task, including overactivation of regions usually involved in VSTM (lateral occipital, precentral gyrus, and postcentral gyrus), recruitment of regions that typically are not involved in VSTM (superior/middle temporal gyrus and supramarginal gyrus), and lower activation of frontal brain regions (inferior frontal gyrus). These patterns of activation were modulated by the age at the time of cancer onset (P = .01) because activity was found to be reduced in participants who were younger at diagnosis. CONCLUSIONS: The results of the current study suggest a pattern of neural inefficiency and compensatory activity during VSTM in survivors of ALL.
Asunto(s)
Lóbulo Frontal/fisiopatología , Memoria a Corto Plazo , Fenómenos Fisiológicos Oculares , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatología , Adulto , Supervivientes de Cáncer , Niño , Femenino , Lóbulo Frontal/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico por imagen , Adulto JovenRESUMEN
This paper is a revised and updated edition of a previous description of the Quebec Newborn Twin Study (QNTS), an ongoing prospective longitudinal follow-up of a birth cohort of twins born between 1995 and 1998 in the greater Montreal area, Québec, Canada. The goal of QNTS is to document individual differences in the cognitive, behavioral, and social-emotional aspects of developmental health across childhood, their early genetic and environmental determinants, as well as their putative role in later social-emotional adjustment, school, health, and occupational outcomes. A total of 662 families of twins were initially assessed when the twins were aged 6 months. These twins and their family were then followed regularly. QNTS now has 16 waves of data collected or planned, including 5 in preschool. Over the last 24 years, a broad range of physiological, cognitive, behavioral, school, and health phenotypes were documented longitudinally through multi-informant and multimethod measurements. QNTS also entails extended and detailed multilevel assessments of proximal (e.g., parenting behaviors, peer relationships) and distal (e.g., family income) features of the child's environment. QNTS children and a subset of their parents have been genotyped, allowing for the computation of a variety of polygenic scores. This detailed longitudinal information makes QNTS uniquely suited for the study of the role of the early years and gene-environment transactions in development.
Asunto(s)
Enfermedades en Gemelos/epidemiología , Sistema de Registros/estadística & datos numéricos , Proyectos de Investigación/normas , Gemelos Dicigóticos/estadística & datos numéricos , Gemelos Monocigóticos/estadística & datos numéricos , Adolescente , Adulto , Niño , Preescolar , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/genética , Trastornos del Conocimiento/psicología , Discapacidades del Desarrollo/epidemiología , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/psicología , Enfermedades en Gemelos/genética , Enfermedades en Gemelos/psicología , Femenino , Estudios de Seguimiento , Interacción Gen-Ambiente , Humanos , Incidencia , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Participación del Paciente , Selección de Paciente , Estudios Prospectivos , Quebec/epidemiología , Gemelos Dicigóticos/genética , Gemelos Dicigóticos/psicología , Gemelos Monocigóticos/genética , Gemelos Monocigóticos/psicología , Adulto JovenRESUMEN
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Because of major improvements in treatment protocols, the survival rate now exceeds 80%. However, ALL treatments can cause long-term neurocognitive sequelae, which negatively impact academic achievement and quality of life. Therefore, cognitive sequelae need to be carefully evaluated. The DIVERGT is a battery of tests proposed as a screening tool, sensitive to executive function impairments in children and adolescent cancer survivors. Our study aimed at verifying the predictive value of the DIVERGT on general cognitive functioning in adult long-term survivors of ALL. METHODS: ALL survivors completed the DIVERGT 13.4 years, on average, after remission (N = 247). In addition, 49 of these survivors (equally selected amongst those with low, average, and high DIVERGT scores) as well as 29 controls completed a more comprehensive neuropsychological evaluation within a 3-year period from DIVERGT administration. Multivariate regression analysis was used to assess the predictive value of the DIVERGT on general intelligence, mathematics, verbal memory, and working memory. As a follow-up analysis, three performance groups were created based on the DIVERGT results. Multivariate analysis of variance (MANOVA) assessed neuropsychological differences between groups. RESULTS: The DIVERGT accurately predicted General Ability Index (GAI) (P < 0.0001), mathematics (P < 0.0001) and verbal memory (P = 0.045). Moreover, the low-performance group consistently had poorer performance than the high-performance and control groups on the neuropsychological tests. CONCLUSION: The DIVERGT is a useful, time-effective screening battery for broader neurocognitive impairments identification in long-term adult ALL survivors. It could be implemented as routine examination in cancer follow-up clinics.
Asunto(s)
Trastornos del Conocimiento/etiología , Tamizaje Masivo/métodos , Pruebas Neuropsicológicas , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicología , Sobrevivientes/psicología , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/epidemiología , Irradiación Craneana/efectos adversos , Femenino , Humanos , Masculino , Matemática , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/epidemiología , Trastornos de la Memoria/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Conducta Verbal , Adulto JovenRESUMEN
BACKGROUND: Recent research has suggested that long-term pediatric cancer survivors were at risk of important physical and psychological morbidities. To date, we do not know to what extent functional health status contributes to psychological risk and which domains are most important. The aim of this study was to systematically explore which functional domain could explain anxiety, depression, and distress symptoms. PROCEDURE: We used data available for 105 adolescents and 182 adults successfully treated for childhood acute lymphoblastic leukemia at two Canadian sites part of the PETALE cohort. Participants were ≥5 years postdiagnosis, aged 22 ± 6 years, 52% female, and 49% acute lymphoblastic leukemia high-risk status. The contribution of health functional status (15D/16D questionnaires) to self-reported anxiety, depression, and distress (Beck scales and distress thermometer) was evaluated using adjusted logistic regression models. RESULTS: Prevalence rates found for mild-severe anxiety, depression, and distress were 14%, 21%, and 30% among adolescents and 27%, 20%, and 19% among adults. Frequent health domains associated with psychological risk were sleeping and breathing in adolescents, and vitality/fatigue, discomfort/symptoms, mental function, and sleeping in adults. Mental function was systematically associated with psychological risk across age groups (median OR = 10.00, 95% CI 3.01-33.71). Exploratory mediation bootstrapping analyses suggested that the effect on psychological risk of overall health status and mental function problems was partly explained by social/work/school functioning. CONCLUSION: The results identified important functional health domains that could be targeted for interventions preventing psychological risk: vitality/fatigue, discomfort/symptoms, sleeping, and mental function issues. Health domains probably affect mood partly by limiting social/work/school functioning.
Asunto(s)
Supervivientes de Cáncer/psicología , Estado de Salud , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Ansiedad/epidemiología , Ansiedad/etiología , Estudios de Cohortes , Depresión/epidemiología , Depresión/etiología , Femenino , Humanos , Masculino , Prevalencia , Estrés Psicológico/epidemiología , Estrés Psicológico/etiología , Adulto JovenRESUMEN
BACKGROUND: Childhood cancer survivorship issues represent an established public health challenge. Most late adverse effects (LAEs) have been demonstrated to be time and treatment dependent. The PETALE study is a multidisciplinary research project aiming to comprehensively characterize LAEs and identify associated predictive biomarkers in childhood acute lymphoblastic leukemia (cALL) survivors. METHODS: cALL survivors treated at Sainte-Justine University Health Center with Dana-Farber Cancer Institution-ALL protocols 87-01 through 2005-01 were eligible. During Phase I of the study, the participants underwent comprehensive clinical, biologic, and psychosocial investigation targeting metabolic syndrome, cardiotoxicity, bone morbidity, neurocognitive problems, and quality of life issues. Whole-exome sequencing was performed for all participants. Subjects identified with an extreme phenotype during Phase I were recalled for additional testing (Phase II). RESULTS: Phase I included 246 survivors (recall rate 71.9%). Of those, 85 participants completed Phase II (recall rate 88.5%). Survivors agreeing to participate in Phase I (n = 251) were similar to those who refused (n = 31) in terms of relapse risk profile, radiotherapy exposure, and age at the time of study. Participants, however, tended to be slightly older at diagnosis (6.1 vs. 4.7 years old, P = 0.08), with a higher proportion of female agreeing to participate compared with males (93.2 vs. 86.5%, P = 0.07). CONCLUSION: The PETALE study will contribute to comprehensively characterize clinical, psychosocial, biologic, and genomic features of cALL survivors using an integrated approach. Expected outcomes include LAE early detection biomarkers, long-term follow-up guidelines, and recommendations for physicians and health professionals.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Enfermedades Óseas , Cardiopatías , Síndrome Metabólico , Trastornos Neurocognitivos , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Enfermedades Óseas/epidemiología , Enfermedades Óseas/etiología , Enfermedades Óseas/metabolismo , Niño , Preescolar , Femenino , Cardiopatías/epidemiología , Cardiopatías/etiología , Cardiopatías/metabolismo , Humanos , Lactante , Masculino , Síndrome Metabólico/epidemiología , Síndrome Metabólico/metabolismo , Trastornos Neurocognitivos/epidemiología , Trastornos Neurocognitivos/etiología , Trastornos Neurocognitivos/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , SobrevivientesRESUMEN
Objectives: To understand why some long-term childhood cancer survivors experience positive adjustment in the long run,[Q1] this study aimed to (1) explore associations between well-being, health status, social support, and emotion regulation (ER) strategies in a cohort of long-term childhood lymphoblastic leukemia (cALL) survivors, (2) identify the individual contribution of each ER strategy to well-being (3) and their interaction with social support. Methods: We used data from 92 participants from the PETALE cohort (51% female, aged 24 ± 7 years). Measures included well-being (WHO-5), health status (15D), social support (SSQ-6), cognitive reappraisal and expressive suppression (ERQ), and emotional processing and expression (EAC). We modeled the odds of high well-being adjusting for health status in logistic regressions and explored the moderating role of social support with bootstrap techniques. Independent of clinical history, high well-being was associated with better health status, higher social support, more frequent use of cognitive reappraisal and emotional processing. Results: We found a main contribution of emotional processing to well-being (OR = 2.12, 95% CI = 1.09-5.37). The interaction between low suppression and high social support was significant (OR = .40, 95% CI = .13-.79). Probabilities for high well-being were 96% when expressive suppression was low and social support was high. Results suggest approaching one's own emotions may contribute to well-being in long-term childhood cancer survivors. Clinical implications: Combining curbing emotional suppression with promoting supportive social environment could be a promising target for future supportive care interventions in survivors.
RESUMEN
Acute lymphoblastic leukemia (ALL) stands as the most prevalent form of pediatric cancer in North America, with a current five-year survival rate of 85%. While more children achieved ALL remission and transition into adulthood, the prevalence of long-term treatment-related effects, especially neurocognitive sequelae, remains significant. This study pursues two objectives. Firstly, it investigates if Magnetization Transfer Ratio (MTR), a method assessing myelin integrity, is sensitive to white matter (WM) microstructural changes in long-term ALL survivors and whether these relate to cognitive impairments. Secondly, it examines the dose-related effects of chemotherapy agents on the MTR and its relationship to other risk factors such as female sex, early age diagnosis, and cranial radiotherapy. Magnetization transfer imaging was utilized to assess WM integrity in 35 survivors at a mean of 18.9 years after the onset of ALL (range since diagnosis: 6.9-26.8). Additionally, 21 controls matched for age, sex, and education level, with no history of cancer, were included. MTR was extracted from both the entire brain's WM and the corpus callosum through semi-automated procedures. The results indicated lower MTR means in survivors, which is linked to cognitive function. Negative associations between MTR means and intrathecal agents' (MTX, cytarabine, and hydrocortisone) cumulative doses received were highlighted. This study offers valuable insights into the connections between myelin deterioration, cognitive impairment, and the implications of IT chemotherapy, enhancing our understanding of ALL survivorship dynamics. It underscores MTR's relevance in monitoring neurotoxicity during oncological drug follow-up examinations.
RESUMEN
Methylphenidate (MPH) has been previously shown to increase resting energy expenditure (REE) in individuals of normal weight; however, the effects on individuals living with obesity are currently unknown. Ten individuals living with obesity were randomly assigned to undergo 60 days of MPH administration with a daily dose of 0.5 mg/kg body weight or a placebo control. REE was measured before and after the 60-day intervention. There was a trend toward significance for group × time interaction on REE (p = 0.082) with a large effect size (η2 = 0.331), with MPH administration increasing REE compared to a decrease in placebo control. Preliminary findings from this pilot study show that MPH has the potential to counter the adaptive thermogenic process commonly seen in weight loss. This is a unique finding among pharmacotherapies, as no approved obesity drugs measurably impact REE.