Development and Use of a Web-based Data Management System for a Randomized Clinical Trial of Adolescents and Young Adults

Recent advances in technology provide support for multi-site, web-based data entry systems and the storage of data in a centralized location, resulting in immediate access to data for investigators, reduced participant burden and human entry error, and improved integrity of clinical trial data. The purpose of this paper is to describe the development of a comprehensive, web-based data management system for a multi-site randomized behavioral intervention trial. Strategies used to create this study-specific data management system included interdisciplinary collaboration, design mapping, feasibility assessments, and input from an advisory board of former patients with characteristics similar to the targeted population. The resulting data management system and development strategies provide a template for other behavioral intervention studies

The Resilience in Illness Model Part 2: Confirmatory Evaluation in Adolescents and Young Adults With Cancer

BACKGROUND: Empirically derived and tested models are necessary to develop effective, holistic interventions to improve positive health outcomes in adolescents and young adults (AYA) with cancer, yet few exist. This article is the second of 2 articles reporting on evaluation of the Resilience in Illness Model (RIM) as a predictive model to guide positive health research and practice. OBJECTIVE: The aim of this study was to report the confirmatory model evaluation of the RIM. METHODS: A confirmatory evaluation of RIM was done using baseline data from a sample of 113 AYA aged 11 to 24 years who were undergoing hematopoietic stem cell transplant and enrolled in a randomized controlled trial of a behavioral intervention to enhance resilience. Data were analyzed using latent variable structural equation modeling. RESULTS: Goodness-of-fit indices supported RIM as a confirmed model that accounted for large amounts of variance in the outcomes of self-transcendence (62%) and resilience (72%), and in 3 of 5 mediators, specifically social integration (74%), courageous coping (80%), and hope-derived meaning (87%), as well as small to moderate amounts of variance in the remaining mediators of defensive coping (1%) and family environment (35%). CONCLUSIONS: Findings establish the RIM as a plausible predictive framework for explaining ways AYA with cancer transcend their illness and achieve resilience resolution and for guiding intervention studies in this population. Additional research is needed to explore RIM's transferability based on stage of illness, other chronic diseases, and cultural diversity. IMPLICATIONS FOR PRACTICE: Results support the RIM as an appropriate guide for developing and evaluating interventions to foster positive adjustment in AYA with cancer

Dental side effects of long-term obstructive sleep apnea therapy:a 10-year follow-up study

OBJECTIVES: Patients with obstructive sleep apnea (OSA) are usually treated with either mandibular advancement device (MAD) or continuous positive airway pressure (CPAP) therapy. The objective of this study is to evaluate changes in dental occlusion associated with long-term MAD and CPAP therapy. MATERIALS AND METHODS: Data from 14 OSA patients using MAD and 17 OSA patients using CPAP therapy were evaluated at baseline, 2-year and 10-year follow-up. Changes in dental occlusion were analyzed from dental plaster casts with a digital sliding caliper. RESULTS: At 2-year follow-up, MAD therapy resulted in significant dental changes when compared with baseline values. In MAD therapy, overjet and overbite decreased with 1.1 ± 1.8 mm and 1.1 ± 1.2 mm respectively. With CPAP therapy overjet and overbite decreased significantly with 0.2 ± 0.5 mm and 0.3 ± 0.5 mm, respectively. Both groups also showed significant changes in molar occlusion. After a 10-year follow-up, significant and more pronounced changes were seen in overjet and overbite. In MAD therapy, overjet and overbite decreased with 3.5 ± 1.5 mm and 2.9 ± 1.5 mm respectively when compared with baseline values. In CPAP therapy, overjet and overbite decreased with 0.7 ± 1.5 mm and 0.8 ± 1.4 mm respectively when compared with baseline values. CONCLUSIONS: This study demonstrates that MAD and CPAP therapy result in significant changes in dental occlusion. These changes appear progressive and more pronounced with MAD compared to CPAP therapy. CLINICAL RELEVANCE: Long-term OSA treatment results in significant dental side effects that may progress over time. Informed consent is fundamental before starting MAD treatment and individualized long-term follow-up is of eminent importance

Recruitment strategies and rates of a multi-site behavioral intervention for adolescents and young adults with cancer

INTRODUCTION: To provide an overview of factors related to recruitment of adolescents and young adults (AYA) into research and recruitment rates and reasons for refusal from a multicenter study entitled "Stories and Music for Adolescent/Young Adult Resilience during Transplant" (SMART). METHODS: A randomized clinical trial study design was used. The settings included 9 hospitals. The sample included AYAs (aged 11-24 years) who were undergoing a stem cell transplant. Several instruments were used to measure symptom distress, coping, resilience, and quality of life in AYA with cancer. RESULTS: A total of 113 AYA were recruited (50%) for this study. Strategies were refined as the study continued to address challenges related to recruitment. We provide a description of recruitment strategies and an evaluation of our planning, implementing, and monitoring of recruitment rates for the SMART study. DISCUSSION: When designing a study, careful consideration must be given to factors influencing recruitment as well as special considerations for unique populations. Dissemination of strategies specific to unique populations will be helpful to the design of future research studies

Impact of Reclassification of Oncocytic and Follicular Thyroid Carcinoma by the 2022 WHO Classification

Background The 2022 WHO Classification categorizes oncocytic (OTC) and follicular thyroid carcinoma (FTC), based on the degree of capsular and vascular invasion, into minimally invasive (MI), encapsulated angio-invasive (EA), and widely invasive tumors (WI). While associations with clinical outcomes have been studied extensively in FTC, robust clinical data are lacking for OTC. We aimed to investigate the impact of the reclassification of OTC and FTC by the 2022 WHO Classification on clinical outcomes.Methods All adult OTC and FTC patients treated at the Erasmus MC (the Netherlands) between 2000 and 2016 were retrospectively included. All tumors were extensively revised by 2 independent pathologists, facilitated by Palga: Dutch Pathology Databank. Kaplan-Meier curves were used to study the association of the 2004 and 2022 WHO Classification with overall survival, disease-specific survival (DSS), recurrence-free survival, and radioactive iodine (RAI)-refractory disease.Results Among 52 OTC and 89 FTC patients, 15 (28.8%) OTC and 34 (38.2%) FTC tumors were reclassified as EAOTC or EAFTC. The 2022 WHO Classification substantially improved risk stratification in both subtypes for DSS, compared to the 2004 edition. Ten-year DSS rates were 100% for MIOTC, 92.9% for EAOTC, and 56.5% for WIOTC, compared to 100% (MIOTC) and 64.2% (WIOTC) following the 2004 WHO Classification. For FTC and RAI-refractory disease, similar trends were observed.Conclusion Classification of OTC and FTC into 3 subcategories as defined by the 2022 WHO Classification substantially improves discrimination between low-, intermediate-, and high-risk patients, especially for DSS and RAI-refractory disease

Effect of acute hyperglycaemia and/or hyperinsulinaemia on proinflammatory gene expression, cytokine production and neutrophil function in humans

AIMS: Type 2 diabetes is frequently associated with infectious complications. Swift activation of leucocytes is important for an adequate immune response. We determined the selective effects of hyperglycaemia and hyperinsulinaemia on lipopolysaccharide (LPS)-induced proinflammatory gene expression and cytokine production in leucocytes and on neutrophil functions. METHODS: Six healthy humans were studied on four occasions for 6 h during: (i) lower insulinaemic euglycaemic clamp, (ii) lower insulinaemic hyperglycaemic clamp, (iii) hyperinsulinaemic euglycaemic clamp, and (iv) hyperinsulinaemic hyperglycaemic clamp. Target levels of plasma glucose were 12.0 mmol/l (hyperglycaemic clamps) or 5.0 mmol/l (euglycaemic clamps). Target plasma insulin levels were 400 pmol/l (hyperinsulinaemic clamps) or 100 pmol/l (lower insulinaemic clamps). RESULTS: Hyperglycaemia reduced LPS-induced mRNA expression of nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor alpha (NFKBIA), interleukin-1 alpha (IL1A) and chemokine (C-C motif) ligand 3 (CCL3), whereas during hyperinsulinaemia enhanced mRNA levels occurred in six out of eight measured inflammation-related genes, irrespective of plasma glucose levels. Combined hyperglycaemia and hyperinsulinaemia led to enhanced IL1A, interleukin-1 beta (IL1B) and CCL3 mRNA levels upon LPS stimulation. Neither hyperglycaemia nor hyperinsulinaemia altered cytokine protein production, neutrophil migration, phagocytic capacity or oxidative burst activity. CONCLUSIONS: These results suggest that short-term hyperglycaemia and hyperinsulinaemia influence the expression of several inflammatory genes in an opposite direction, that the acute effects of hyperinsulinaemia on inflammatory mRNA levels may be stronger than those of hyperglycaemia, and that the effects of insulin, in particular, may be relevant in the concurrent presence of hyperglycaemi

Carleson measures for Hilbert spaces of analytic functions on the complex half-plane

The notion of a Carleson measure was introduced by Lennart Carleson in his proof of the Corona Theorem for H∞(D). In this paper we will define it for certain type of reproducing kernel Hilbert spaces of analytic functions of the complex half-plane, C+, which will include Hardy, Bergman and Dirichlet spaces. We will obtain several necessary or sufficient conditions for a positive Borel measure to be Carleson by preforming tests on reproducing kernels, weighted Bergman kernels, and studying the tree model obtained from a decomposition of the complex half-plane. The Dirichlet space will be investigated in detail as a special case. Finally, we will present a control theory application of Carleson measures in determining admissibility of controls in well-posed linear evolution equations

Weighted composition operators on the Dirichlet space: boundedness and spectral properties

Boundedness of weighted composition operators W u,φ acting on the classical Dirichlet space D as W u,φ f=u(f∘φ) is studied in terms of the multiplier space associated to the symbol φ , i.e., M(φ)={u∈D:W u,φ is bounded on D} . A prominent role is played by the multipliers of the Dirichlet space. As a consequence, the spectrum of W u,φ in D whenever φ is an automorphism of the unit disc is studied, extending a recent work of Hyvärinen et al. (J. Funct. Anal. 265:1749–1777, 2013) to the context of the Dirichlet space

Randomized clinical trial of therapeutic music video intervention for resilience outcomes in adolescents/young adults undergoing hematopoietic stem cell transplant: a report from the Children's Oncology Group

BACKGROUND: To reduce the risk of adjustment problems associated with hematopoietic stem cell transplant (HSCT) for adolescents/young adults (AYAs), we examined efficacy of a therapeutic music video (TMV) intervention delivered during the acute phase of HSCT to: 1) increase protective factors of spiritual perspective, social integration, family environment, courageous coping, and hope-derived meaning; 2) decrease risk factors of illness-related distress and defensive coping; and 3) increase outcomes of self-transcendence and resilience. METHODS: This was a multisite randomized, controlled trial (COG-ANUR0631) conducted at 8 Children's Oncology Group sites involving 113 AYAs aged 11-24 years undergoing myeloablative HSCT. Participants, randomized to the TMV or low-dose control (audiobooks) group, completed 6 sessions over 3 weeks with a board-certified music therapist. Variables were based on Haase's Resilience in Illness Model (RIM). Participants completed measures related to latent variables of illness-related distress, social integration, spiritual perspective, family environment, coping, hope-derived meaning, and resilience at baseline (T1), postintervention (T2), and 100 days posttransplant (T3). RESULTS: At T2, the TMV group reported significantly better courageous coping (Effect Size [ES], 0.505; P = .030). At T3, the TMV group reported significantly better social integration (ES, 0.543; P = .028) and family environment (ES, 0.663; P = .008), as well as moderate nonsignificant effect sizes for spiritual perspective (ES, 0.450; P = .071) and self-transcendence (ES, 0.424; P = .088). CONCLUSIONS: The TMV intervention improves positive health outcomes of courageous coping, social integration, and family environment during a high-risk cancer treatment. We recommend the TMV be examined in a broader population of AYAs with high-risk cancers