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BACKGROUND: Previous studies have reported brain structure abnormalities in conduct disorder (CD), but it is unclear whether these neuroanatomical alterations mediate the effects of familial (genetic and environmental) risk for CD. We investigated brain structure in adolescents with CD and their unaffected relatives (URs) to identify neuroanatomical markers of familial risk for CD. METHODS: Forty-one adolescents with CD, 24 URs of CD probands, and 38 healthy controls (aged 12-18), underwent structural magnetic resonance imaging. We performed surface-based morphometry analyses, testing for group differences in cortical volume, thickness, surface area, and folding. We also assessed the volume of key subcortical structures. RESULTS: The CD and UR groups both displayed structural alterations (lower surface area and folding) in left inferior parietal cortex compared with controls. In contrast, CD participants showed lower insula and pars opercularis volume than controls, and lower surface area and folding in these regions than controls and URs. The URs showed greater folding in rostral anterior cingulate and inferior temporal cortex than controls and greater medial orbitofrontal folding than CD participants. The surface area and volume differences were not significant when controlling for attention-deficit/hyperactivity disorder comorbidity. There were no group differences in subcortical volumes. CONCLUSIONS: These findings suggest that alterations in inferior parietal cortical structure partly mediate the effects of familial risk for CD. These structural changes merit investigation as candidate endophenotypes for CD. Neuroanatomical changes in medial orbitofrontal and anterior cingulate cortex differentiated between URs and the other groups, potentially reflecting neural mechanisms of resilience to CD.
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Transtorno da Conduta , Humanos , Adolescente , Transtorno da Conduta/diagnóstico por imagem , Predisposição Genética para Doença , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/patologia , Lobo Temporal/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
PURPOSE: To explore symptoms and disease impacts of Crohn's disease and to develop a new patient-reported outcomes (PRO) measure according to industry best practices. METHODS: A conceptual model of relevant symptoms experienced by patients with Crohn's disease was developed following a literature review. Three rounds of combined qualitative semi-structured concept elicitation and cognitive debriefing interviews with 36 patients (≥ 16 years) with Crohn's disease and 4 clinicians were conducted to further explore the most commonly reported and most bothersome symptoms to patients. Interview results were used to update the conceptual model as well as items and response options included in The Crohn's Disease Diary, a new PRO measure. RESULTS: All patients (N = 36) reported abdominal pain, loose or liquid bowel movements, and high or increased frequency of bowel movements, with most reporting these symptoms spontaneously (100%, 92%, and 75%, respectively). All patients reported bowel movement urgency, but 61% reported this symptom only when probed. Most also reported that symptoms impacted activities of daily living, work/school, and emotional, social, and physical functioning (overall, 78%-100%; spontaneously, 79% - 92%). Data regarding core symptoms of Crohn's disease from clinician concept elicitation interviews supported patient data. The 17-item Crohn's Disease Diary assesses core symptoms and impacts of Crohn's disease over 24 h, and extraintestinal manifestations over 7 days. The content validity of the diary was confirmed during cognitive debriefing interviews. CONCLUSION: The Crohn's Disease Diary is a new PRO measure for the assessment of Crohn's disease symptoms and impacts, developed according to industry best practices.
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Doença de Crohn , Humanos , Atividades Cotidianas , Qualidade de Vida/psicologia , Pesquisa Qualitativa , Dor AbdominalRESUMO
OBJECTIVE: Diversity and equity in medicine remain pivotal to care delivery. Data analysis on sex and racial diversity of pain medicine fellowship trainees and faculty in the United States are scant. We sought to characterize demographic and retention patterns among pain medicine fellows and faculty, who represent the emerging chronic pain management workforce. DESIGN: cross-sectional retrospective analysis. METHOD: We conducted an analysis of data from the American Association of Medical Colleges (AAMC) and the United States Accreditation Council on Graduate Medical Education (ACGME)-approved residency and fellowship training-programs for each year from 2009 through 2019, inclusively. We compared changes in sex, racial/ethnicity composition and retention rates of fellows and faculty in the United States by practice setting. RESULTS: From 2009 to 2019, there was a 14% increase in the number of ACGME pain fellowship programs. From 2009 to 2019, the ratio of men to women pain fellows ranged from 5:1 to 3.7:1. Compared with their self-identified White peers, Asian (OR 0.44; 95% CI: 0.34-0.58), Black (OR 0.46; 95% CI: 0.30-0.72), and Native American/Alaskan Native (OR 0.26; 95% CI: 0.08-0.80) identifying individuals had significantly lower odds of being a pain fellow, P < 0.05. There was no significant difference in female (OR = 0.4, 95% CI: 0.148-1.09) and Black (OR 0.36; 95% CI: 0.11-1.12) program-directors. Pain-fellow in-state retention was 53%. CONCLUSIONS: The demographics of pain medicine training programs reflect a persistent male vs. female gap with underrepresentation of racial minorities. Further research is needed to elucidate reasons underlying these disparities.
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Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Estudos Transversais , Docentes , Feminino , Humanos , Masculino , Dor , Estudos Retrospectivos , Estados UnidosRESUMO
OBJECTIVES: Thresholds for the minimally important difference (MID) or responder definition (RD) in health-related quality-of-life (HRQoL) scores are required to interpret the impact of an intervention or change in the trajectory of the condition which is meaningful to patients. This study aimed to establish MID and RD for the European Organisation for Research and Treatment of Cancer Quality of Life Multiple Myeloma questionnaire (EORTC QLQ-MY20). METHODS: A novel mixed-methods approach was applied by utilizing both existing clinical trial data and prospective patient interviews. Anchor-based, distribution-based, and qualitative-based estimates of meaningful change were triangulated to form recommended RDs for each scale of the EORTC QLQ-MY20. Anchor-based MIDs were summarized using weighted correlation. RESULTS: Recommended MIDs were as follows: Disease Symptoms (DS 10 points), Side Effects of Treatment (SE 10 points), Body Image (BI 13 points), and Future Perspective (FP 9 points). Recommended RDs were as follows: DS (16 improvement; 11 worsening), SE (6 improvement; 9 worsening), BI (33 improvement; 33 worsening), and FP (11 improvement; 11 worsening). CONCLUSIONS: The study generated estimates of the MID and RD for each scale of the EORTC QLQ-MY20. Published estimates will enable investigators and clinicians to adopt these as standard for interpretation and for hypothesis testing. Consequently, analyses from trials of different interventions can be more comparable.
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Mieloma Múltiplo/terapia , Qualidade de Vida , Inquéritos e Questionários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
INTRODUCTION: Diary-derived symptom score and rescue medication use endpoints, such as symptom-free days (SFDs) and rescue medication-free days (RFD), are frequently used as clinical trial endpoints. Estimates of meaningful change for SFDs and RFDs have not been generated in pediatric populations. This research aimed to generate evidence supporting estimates of the individual within-patient changes that constitute an important or meaningful change in SFDs, RFDs, and updated estimates on the Childhood Asthma Control Test (C-ACT) in pediatric asthma populations aged 5-11 years. METHODS: Semistructured, qualitative interviews were conducted with children (ages 8-11 years) who had asthma and parents/caregivers of children (4-11 years) with asthma. Before the interview (4-9 days) participants were asked to complete a morning and evening diary. RESULTS: On average, parent/caregiver estimates of the difference in SFDs between a "very bad" and a "little bad" week for their children's asthma were largely concordant with the values reported by their children (differences of 1.8 and 1.4 SFDs, respectively). Both parents/caregivers and children were able to articulate what a meaningful level of change would be on the C-ACT at the item level. This qualitative study generated C-ACT item-level meaningful change estimates in the region of 1-3 category change, which potentially suggests that, if scaled up to represent C-ACT total score, this would lead to change estimates of 7-15 points. CONCLUSIONS: Our findings suggest that both children with asthma and parents/caregivers can quantitatively estimate and to some extent qualitatively articulate meaningful change in SFDs and RFDs.
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Antiasmáticos/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto/normas , Ensaios Clínicos Fase IV como Assunto/normas , Uso Significativo/normas , Asma/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Uso Significativo/tendências , Prontuários Médicos/normasRESUMO
BACKGROUND: Neuroimaging methods that allow researchers to investigate structural covariance between brain regions are increasingly being used to study psychiatric disorders. Structural covariance analyses are particularly well suited for studying disorders with putative neurodevelopmental origins as they appear sensitive to changes in the synchronized maturation of different brain regions. We assessed interregional correlations in cortical thickness as a measure of structural covariance, and applied this method to investigate the coordinated development of different brain regions in conduct disorder (CD). We also assessed whether structural covariance measures could differentiate between the childhood-onset (CO-CD) and adolescence-onset (AO-CD) subtypes of CD, which may differ in terms of etiology and adult outcomes. METHODS: We examined interregional correlations in cortical thickness in male youths with CO-CD or AO-CD relative to healthy controls (HCs) in two independent datasets. The age range in the Cambridge sample was 16-21 years (mean: 18.0), whereas the age range of the Southampton sample was 13-18 years (mean: 16.7). We used FreeSurfer to perform segmentations and applied structural covariance methods to the resulting parcellations. RESULTS: In both samples, CO-CD participants displayed a strikingly higher number of significant cross-cortical correlations compared to HC or AO-CD participants, whereas AO-CD participants presented fewer significant correlations than HCs. Group differences in the strength of the interregional correlations were observed in both samples, and each set of results remained significant when controlling for IQ and comorbid attention-deficit/hyperactivity disorder symptoms. CONCLUSIONS: This study provides new evidence for quantitative differences in structural brain organization between the CO-CD and AO-CD subtypes, and supports the hypothesis that both subtypes of CD have neurodevelopmental origins.
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Córtex Cerebral/anatomia & histologia , Transtorno da Conduta/patologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idade de Início , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Transtorno da Conduta/diagnóstico por imagem , Transtorno da Conduta/fisiopatologia , Humanos , Delinquência Juvenil , Masculino , Adulto JovemRESUMO
INTRODUCTION: Chronic weight management and treatments for type 2 diabetes (T2D) involve a combination of lifestyle-based (diet, exercise) and pharmaceutical interventions. In people with obesity or T2D, understanding the impact of drivers/triggers on appetite and eating behaviors can be crucial to successful medical management. This study aimed to characterize perceptions and experiences regarding appetite and eating behaviors among people with obesity or T2D and identify drivers/triggers of food choices. METHODS: This non-interventional, cross-sectional, qualitative study utilized semi-structured concept elicitation interviews to explore the perceptions of people with obesity and/or T2D around appetite, eating behaviors and drivers/triggers of food choices. Adult US residents (≥ 18 years) with stable body weight (± 5 kg) in the 3 months preceding participation were included in the study. RESULTS: Forty-five participants (obesity: n = 15; overweight: n = 10; T2D: n = 20) were interviewed. Interviews were audio-recorded and transcribed verbatim for analysis. A subset of participants described eating behaviors on smartphone-based app tasks over 5 days. Most (> 96%) discussed the influence of hunger, cravings and satiety on food choices. Participants identified 22 drivers/triggers (including health, 95.6%; culture/heritage, 93.3%; location, 91.1%; stress, 88.8%). Participants also discussed associations between drivers/triggers and eating behavior concepts (appetite, hunger, cravings, satiety, motivation/determination). A conceptual model illustrating eating behavior concepts and related drivers/triggers was developed. The concept elicitation interviews identified a multitude of drivers and triggers and characterized the association of such drivers/triggers with seven core patient-reported concepts encompassing eating behaviors. CONCLUSION: The findings build upon existing models of factors influencing food choices. Findings confirm prior research regarding impact of drivers/triggers on food choice in people with obesity and T2D and indicate underlying disease state does not appear to influence eating behaviors in people with stable body weight.
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Apetite , Diabetes Mellitus Tipo 2 , Comportamento Alimentar , Obesidade , Pesquisa Qualitativa , Humanos , Diabetes Mellitus Tipo 2/psicologia , Obesidade/psicologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Adulto , Comportamento Alimentar/psicologia , Idoso , Preferências Alimentares/psicologiaRESUMO
AIMS: The aim of this study was to explore the experiences, values and preferences of people living with relapsing multiple sclerosis (PLwRMS) focusing on their treatments and what drives their treatment preferences. METHODS: In-depth, semi-structured, qualitative telephone interviews were conducted using a purposive sampling approach with 72 PLwRMS and 12 health care professionals (HCPs, MS specialist neurologists and nurses) from the United Kingdom, United States, Australia and Canada. Concept elicitation questioning was used to elicit PLwRMS' attitudes, beliefs and preferences towards features of disease-modifying treatments. Interviews with HCPs were conducted to inform on HCPs' experiences of treating PLwRMS. Responses were audio recorded and transcribed verbatim and then subjected to thematic analysis. RESULTS: Participants discussed numerous concepts that were important to them when making treatment decisions. Levels of importance participants placed on each concept, as well as reasons underpinning importance, varied substantially. The concepts with the greatest variability in terms of how much PLwRMS found them to be important in their decision-making process were mode of administration, speed of treatment effect, impact on reproduction and parenthood, impact on work and social life, patient engagement in decision making, and cost of treatment to the participant. Findings also demonstrated high variability in what participants described as their ideal treatment and the most important features a treatment should have. HCP findings provided clinical context for the treatment decision-making process and supported patient findings. CONCLUSIONS: Building upon previous stated preference research, this study highlighted the importance of qualitative research in understanding what drives patient preferences. Characterized by the heterogeneity of the RMS patient experience, findings indicate the nature of treatment decisions in RMS to be highly individualized, and the subjective relative importance placed on different treatment factors by PLwRMS to vary. Such qualitative patient preference evidence could offer valuable and supplementary insights, alongside quantitative data, to inform decision making related to RMS treatment.
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Esclerose Múltipla , Humanos , Tomada de Decisões , Individualidade , Pesquisa Qualitativa , Avaliação de Resultados da Assistência ao PacienteRESUMO
Background: Peristomal skin complications (PSCs) pose a major challenge for people living with an ostomy. To avoid severe PSCs, it is important that people with an ostomy check their peristomal skin condition on a regular basis and seek professional help when needed. Aim: To validate a new ostomy skin tool (OST 2.0) that will make regular assessment of the peristomal skin easier. Methods: Seventy subjects participating in a clinical trial were eligible for the analysis and data used for the validation. Item-level correlation with anchors, inter-item correlations, convergent validity of domains, test-retest reliability, anchor- and distribution-based methods for assessment of meaningful change were all part of the psychometric validation of the tool. Results: A final tool was established including six patient reported outcome items and automatic assessment of the discolored peristomal area. Follow-up with cognitive debriefing interviews assured that the concepts were considered relevant for people with an ostomy. Conclusion: The OST 2.0 demonstrated evidence supporting its reliability and validity as an outcome measure to capture both visible and non-visible peristomal skin complications.
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Estomia , Dermatopatias , Humanos , Estomia/efeitos adversos , Psicometria , Reprodutibilidade dos Testes , Pele , Dermatopatias/diagnósticoRESUMO
Introduction: This patient preference study sought to quantify the preferences of people living with COPD regarding symptom improvement in the UK, USA, France, Australia and Japan. Methods: The inclusion criteria were people living with COPD aged 40â years or older who experienced ≥1 exacerbation in the previous year with daily symptoms of cough and excess mucus production. The study design included: 1) development of an attributes and levels grid through qualitative patient interviews; and 2) implementation of the main online quantitative survey, which included a discrete choice experiment (DCE) to allow assessment of attributes and levels using hypothetical health state profiles. Preference weights (utilities) were derived from the DCE using hierarchical Bayesian analysis. A preference simulator was developed that enabled different health state scenarios to be evaluated based on the predicted patient preferences. Results: 1050 people living with moderate-to-severe COPD completed the survey. All attributes were considered important when patients determined their preferences in the DCE. In a health state preference simulation, two hypothetical health states (comprising attribute levels) with qualitatively equivalent improvements in A) cough and mucus and B) shortness of breath (SOB) resulted in a clear preference for cough and mucus improved profile. When comparing two profiles with C) daily symptoms improved and D) exacerbations improved, there was a clear preference for the daily symptoms improved profile. Conclusions: People living with moderate-to-severe COPD prefer to reduce cough and mucus production together over improvement of SOB and would prefer to reduce combined daily symptoms over an improvement in exacerbations.
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BACKGROUND: Accurate symptom monitoring is vital when managing pediatric asthma, providing an opportunity to improve control and relieve associated burden. The CHILDHOOD ASTHMA CONTROL TEST (C-ACT) has been validated for asthma control assessment in children; however, there are concerns that response option images used in the C-ACT are not culturally universal and could be misinterpreted. This cross-sectional, qualitative study developed and evaluated alternative response option images using interviews with children with asthma aged 4-11 years (and their parents/caregivers) in the United States, Spain, Poland, and Argentina. Interviews were conducted in two stages (with expert input) to evaluate the appropriateness, understanding and qualitative equivalence of the alternative images (both on paper and electronically). This included comparing the new images with the original C-ACT response scale, to provide context for equivalence results. RESULTS: Alternative response option images included scale A (simple faces), scale B (circles of decreasing size), and scale C (squares of decreasing quantity). In Stage 1, most children logically ranked images using scales A, B and C (66.7%, 79.0% and 70.6%, respectively). However, some children ranked the images in scales B (26.7%) and C (58.3%) in reverse order. Slightly more children could interpret the images within the context of their asthma in scale B (68.4%) than A (55.6%) and C (47.5%). Based on Stage 1 results, experts recommended scales A (with slight modifications) and B be investigated further. In Stage 2, similar proportions of children logically ranked the images used in modified scales A (69.7%) and B (75.7%). However, a majority of children ranked the images in scale B in the reverse order (60.0%). Slightly more children were able to interpret the images in the context of their asthma using scale B (57.6%) than modified scale A (48.5%). Children and parents/caregivers preferred modified scale A over scale B (78.8% and 90.9%, respectively). Compared with the original C-ACT, most children selected the same response option on items using both scales, supporting equivalency. Following review of Stage 2 results, all five experts agreed modified scale A was the optimal response scale. CONCLUSIONS: This study developed alternative response option images for use in the C-ACT and provides qualitative evidence of the equivalency of these response options to the originals.
Accurate monitoring of the symptoms associated with pediatric asthma is important when managing the condition. The CHILDHOOD ASTHMA CONTROL TEST (C-ACT) is a questionnaire widely used to measure asthma severity in young children (aged 411 years). Each question answered by the child in the C-ACT has four possible answer choices. To help children answer, each choice is presented alongside an image of a male child's face ranging from sad to happy. However, there are concerns that the images used are not culturally universal and could be misinterpreteddue to difficulties translating to electronic formats and a lack of differentiation between the images used. Through interviewing children with asthma, we aimed to address these concerns by developing and testing new images. Alternative image options developed included simpler faces, circles of decreasing size and squares of decreasing quantity. Children aged 411 years old were interviewed to test whether they understood the response scale using the new images and if they answered in the same way as with the original images. Interviews were conducted in two stages, with expert guidance at key stages. Results showed that children can interpret and understand the newly developed images and that they answer the questions the same as they would using the original images. These new images have the advantages of being culturally neutral and easier to implement on an electronic device.
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Expectations relating to treatment and survival, and factors influencing treatment decisions are not well understood in adult patients with acute myeloid leukemia. This study analyzed combined findings from a targeted literature review with patient-reported information shared on YouTube to further understand patient perspectives in hematologic cancers and, in particular, acute myeloid leukemia. The targeted literature review included articles concerning patient (aged ≥ 18 years) experiences or perspectives in acute myeloid leukemia or other hematologic cancers. YouTube video selection criteria included patients (aged ≥ 60 years) with self-reported acute myeloid leukemia. In total, 26 articles (13 acute myeloid leukemia-specific and 14 other hematologic cancers, with one relevant to both populations) and 28 videos pertaining to ten unique patients/caregivers were identified. Key concepts reported by patients included the perceived value of survival for achieving personal and/or life milestones, the emotional/psychological distress of their diagnosis, and the uncertainties about life expectancy/prognosis. Effective therapies that could potentially delay progression and extend life were of great importance to patients; however, these were considered in terms of quality-of-life impact and disruption to daily life. Many patients expressed concerns regarding the lack of treatment options, the possibility of side effects, and how their diagnosis and treatment would affect relationships, daily lives, and ability to complete certain tasks. Both data sources yielded valuable and rich information on the patient experience and perceptions of hematologic cancers, in particular for acute myeloid leukemia, and its treatments. Further understanding of these insights could aid discussions between clinicians, patients, and their caregivers regarding treatment decisions, highlight outcomes of importance to patients in clinical studies, and ultimately, inform patient-focused drug development and evaluation.
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Antineoplásicos/uso terapêutico , Tomada de Decisão Compartilhada , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/psicologia , Participação do Paciente/psicologia , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Cuidadores/psicologia , Emoções , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/psicologia , Humanos , Leucemia Mieloide Aguda/epidemiologia , Expectativa de Vida , Masculino , Pessoa de Meia-Idade , Assistência Centrada no Paciente/organização & administração , Qualidade de Vida/psicologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , IncertezaRESUMO
Establishing meaningful change thresholds for Clinical Outcome Assessments (COA) is critical for score interpretation. While anchor- and distribution-based statistical methods are well-established, qualitative approaches are less frequently used. This commentary summarizes and expands on a symposium presented at the International Society for Quality of Life Research (ISOQOL) 2017 annual conference, which provided an overview of qualitative methods that can be used to support understanding of meaningful change thresholds on COAs. Further published literature and additional examples from multiple disease areas which have also qualitatively explored the concept of meaningful change are presented.Semi-structured interviews conducted independently from a clinical trial, exit interviews conducted in the context of a clinical trial, focus groups, vignettes and the Delphi panel method can be used to obtain data regarding meaningful change thresholds, with advantages and disadvantages to each method. Semi-structured interviews using concept elicitation (CE) or cognitive debriefing (CD) methods conducted independently from a clinical trial can be an efficient way to gain in-depth patient/caregiver insights. However, there can be challenges with reconciling heterogeneous data across diverse samples and in interpreting the qualitative insights in the context of quantitative score changes. Semi-structured qualitative interviews using CE/CD methods embedded as exit interviews in a clinical trial context with patients/caregivers can provide insights which can augment quantitative findings based on analysis of clinical trial data. However, there are logistical challenges relating to embedding the interviews in a clinical trial.Focus groups and the Delphi panel method can be valuable for reaching consensus regarding meaningful change thresholds; however, for face-to-face interactions, social desirability bias can affect responses. Finally, using vignettes and taking a mixed methods approach can aid in achieving consensus on the minimum score change endorsed by respondents as a meaningful improvement/decrement. However, the approach can be cognitively challenging for participants and reaching a consensus is not guaranteed.Anchor- and distribution- based methods remain critical in establishing responder definitions. Nonetheless, qualitative data has the potential to provide complementary support that a certain level of change on the target COA, which has been statistically supported, is truly important and meaningful for the target population.
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Adolescents with conduct disorder (CD) and elevated callous-unemotional (CU) traits have been reported to present with a more severe and persistent pattern of antisocial behaviour than those with low levels of CU traits. However, relatively few studies have investigated whether there are differences in brain structure between these subgroups.We acquired diffusion tensor imaging data and used tract-based spatial statistics (TBSS) to compare adolescents with CD and high levels of CU traits (CD/CU+; n = 18, CD and low levels of CU traits (CD/CU-; n = 17) and healthy controls (HC; n = 32) on measures of fractional anisotropy (FA), axial (AD), radial (RD) and mean (MD) diffusivity. Compared to CD/CU- adolescents, those with CD/CU+ presented increased FA and reduced RD and MD (lower diffusivity) in several tracts including: body and splenium of the corpus callosum, right inferior longitudinal fasciculus, ILF; right inferior fronto-occipital fasciculus, IFOF; left superior longitudinal fasciculus, SLF; left cerebral peduncle, bilateral internal capsule, left superior and posterior corona radiata, bilateral thalamic radiation and left external capsule. In addition, relative to CD/CU- individuals, adolescents with CD/CU+ showed lower diffusivity (indexed by reduced RD and MD) in left uncinate fasciculus and bilateral fornix. Finally, relative to healthy controls, CD/CU+ individuals showed lower diffusivity (reduced RD) in the genu and body of the corpus callosum and left anterior corona radiata. These results suggest that CD/CU+ individuals present with white-matter microstructural abnormalities compared to both CD/CU- individuals and age-matched healthy controls. This finding is consistent with emerging evidence suggesting that CD/CU+ represents a distinct subtype of CD, and illustrates the importance of accounting for heterogeneity within CD populations.
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Transtorno da Conduta/patologia , Transtorno da Conduta/fisiopatologia , Emoções/fisiologia , Empatia/fisiologia , Substância Branca/patologia , Adolescente , Transtorno da Conduta/diagnóstico por imagem , Imagem de Tensor de Difusão , Humanos , Masculino , Substância Branca/diagnóstico por imagemRESUMO
Tuberous sclerosis complex (TSC) is a rare genetic disease associated with significant disease burden and considerable impact on health-related quality of life (HRQL). Currently no disease-specific clinical outcome assessments evaluate HRQL in individuals with TSC. A multi-center phase III study EXIST-3 (NCT01713946) assessed the efficacy and safety of two trough exposure ranges (Low exposure, LE: 3-7 ng/mL and high exposure, HE: 9-15 ng/mL) of adjunctive everolimus in patients aged 2-65 years with TSC and refractory partial-onset seizures (N = 366). Three age-specific HRQL measures were included as secondary endpoints including: quality of life in childhood epilepsy (QOLCE; caregiver-report for aged 2- < 11), the Quality of Life in Epilepsy Inventory for Adolescents-48 (QOLIE-AD-48; self-report, aged ≥ 11- < 18), and the Quality of Life in Epilepsy Inventory-31-Problems (QOLIE-31-P; self-report, aged ≥ 18). Intellectual ability was evaluated using the Wechsler Non-Verbal (WNV) Scale of Ability. Post hoc analyses were performed on the core phase primary data from EXIST-3 to evaluate the psychometric properties of the HRQL measures and calculate meaningful change estimates. Results showed that a significant subset of the trial sample (4-21 year olds) scored in the intellectual disability range, as assessed by the WNV. Psychometric analyses of the three epilepsy measures (including reliability, validity, and ability to detect change) supported the appropriateness for use in TSC. Distribution-based meaningful change estimates were generated for each HRQL measure, with estimates for the QOLIE-31-P total score largely consistent with the published literature. To our knowledge, this is the first evaluation using clinical trial data to establish the psychometric properties of the QOLCE, QOLIE-AD-48, and QOLIE-31-P for use in individuals with TSC. These findings increase confidence in the measures as valid and reliable for use in clinical trials and future research in patients with TSC.
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Previous studies have demonstrated increased risk-taking in adolescents with Conduct Disorder (CD) compared with typically developing controls. Increased risk-taking may partly mediate the pathway from genetic or environmental risk to CD. We investigated the familial basis of risk-taking by examining whether the unaffected relatives of CD probands (n = 22) showed heightened risk-taking in a gambling task, in common with affected probands (n = 44). Adolescents with CD were more likely to select risky options than the typically developing controls (n = 37) and unaffected relatives. Our findings confirm the association between CD and increased risk-taking, but suggest that this decision-making style may not have a familial basis.
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Transtorno da Personalidade Antissocial/genética , Transtorno da Personalidade Antissocial/psicologia , Transtorno da Conduta/genética , Transtorno da Conduta/psicologia , Jogo de Azar/genética , Jogo de Azar/psicologia , Assunção de Riscos , Adolescente , Comportamento de Escolha , Tomada de Decisões , Feminino , Humanos , Masculino , Valores de ReferênciaRESUMO
OBJECTIVE: Conduct disorder (CD) is characterized by impulsive, aggressive, and antisocial behaviors that might be related to deficits in empathy and moral reasoning. The brain's default mode network (DMN) has been implicated in self-referential cognitive processes of this kind. METHOD: This study examined connectivity between key nodes of the DMN in 29 adolescent boys with CD and 29 age- and sex-matched typically developing adolescent boys. The authors ensured that group differences in DMN connectivity were not explained by comorbidity with other disorders by systematically controlling for the effects of substance use disorders (SUDs), attention-deficit/hyperactivity disorder (ADHD) symptoms, psychopathic traits, and other common mental health problems. RESULTS: Only after adjusting for co-occurring ADHD symptoms, the group with CD showed hypoconnectivity between core DMN regions compared with typically developing controls. ADHD symptoms were associated with DMN hyperconnectivity. There was no effect of psychopathic traits on DMN connectivity in the group with CD, and the key results were unchanged when controlling for SUDs and other common mental health problems. CONCLUSION: Future research should directly investigate the possibility that the aberrant DMN connectivity observed in the present study contributes to CD-related deficits in empathy and moral reasoning and examine self-referential cognitive processes in CD more generally.
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Comportamento do Adolescente/fisiologia , Córtex Cerebral/fisiopatologia , Transtorno da Conduta/fisiopatologia , Conectoma , Adolescente , Córtex Cerebral/diagnóstico por imagem , Transtorno da Conduta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
OBJECTIVE: the aim of this study is to report satisfaction rates and identify factors predicting satisfaction in the Pennsylvania Workers' Compensation (WC) system. METHODS: Cross-sectional survey data on satisfaction and care experience of injured workers were collected annually for 14 years with 27,712 injured workers responding. RESULTS: The overall response rate was 19.44%. The overall proportion of satisfied workers was 83.97% with a range of 80.43% to 88.13%. Obtaining a correct initial diagnosis [odds ratio (OR)â=â4.26], explanation of WC rights (ORâ=â2.58), and physician explanation of treatment options (ORâ=â1.83) most strongly predicted satisfaction. CONCLUSIONS: Injured worker satisfaction with their medical care exceeded 80% in all years surveyed. Patient perception of a correct initial diagnosis, explanation of WC rights, and explanation of treatment options were the strongest predictors of satisfaction during the 14-year study period.