Bridge study protocol : an international, observational cohort study on the transition of healthcare for adolescents with chronic conditions

Introduction More than 10% of adolescents live with a chronic disease or disability that requires regular medical follow-up as they mature into adulthood. During the first 2 years after adolescents with chronic conditions are transferred to adult hospitals, non-adherence rates approach 70% and emergency visits and hospitalisation rates significantly increase. The purpose of the Bridge study is to prospectively examine associations of transition readiness and care experiences with transition success: young patients' health, health-related quality of life (HRQoL) and adherence to medical appointments as well as costs of care. In addition, we will track patients' growing independence and educational and employment pathways during the transition process. Methods and analysis Bridge is an international, prospective, observational cohort study. Study participants are adolescents with a chronic health condition or disability and their parents/guardians who attended the New Children's Hospital in Helsinki, Finland, or the Royal Children's Hospital (RCH) in Melbourne, Australia. Baseline assessment took place approximately 6 months prior to the transfer of care and follow-up data will be collected 1 year and 2 years after the transfer of care. Data will be collected from patients' hospital records and from questionnaires completed by the patient and their parent/guardian at each time point. The primary outcomes of this study are adherence to medical appointments, clinical health status and HRQoL and costs of care. Secondary outcome measures are educational and employment outcomes. Ethics and dissemination The Ethics Committee for Women's and Children's Health and Psychiatry at the Helsinki University Hospital (HUS/1547/2017) and the RCH Human Research Ethics Committee (38035) have approved the Bridge study protocol. Results will be published in international peer-reviewed journals and summaries will be provided to the funders of the study as well as patients and their parents/guardians.Peer reviewe

Cognitive reserve, executive function, and memory in parkinson’s disease

Cognitive impairment is acknowledged as a feature of Parkinson’s disease (PD), and the most common cognitive declines are in executive function (EF) and memory. Cognitive reserve (CR) may offer some protection against cognitive dysfunction in PD. The present study used two proxies of CR (years of education, premorbid IQ) to examine the relationship between CR and (i) EF (ii) memory in a large PD sample (n = 334). Two aspects of EF were examined, including verbal fluency and planning skills. Two aspects of verbal memory were examined, including immediate recall and delayed recall. For EF, both CR proxies significantly predicted verbal fluency, but only years of education predicted planning skills. Years of education significantly predicted immediate recall, but premorbid IQ did not. Neither CR proxy predicted delayed recall. These findings suggest that CR, in particular years of education, may contribute to EF and memory function in those with PD. A key finding of this study is the varying contribution of CR proxies to different aspects of the same cognitive domain. The findings indicate that using only one proxy has the potential to be misleading and suggest that when testing the relationship between CR and cognition, studies should include tasks that measure different aspects of the cognitive domain(s) of interest

Shorter Disease Duration Is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn's Disease But Not Ulcerative Colitis.

Background & aimsPatients with Crohn's disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration.MethodsWe analyzed data from a retrospective, multicenter, consortium of patients with CD (n = 650) or UC (n = 437) treated with vedolizumab from May 2014 through December 2016. Using time to event analyses, we compared rates of clinical remission, corticosteroid-free remission (CSFR), and endoscopic remission between patients with early-stage (≤2 years duration) and later-stage (>2 years) CD or UC. We used Cox proportional hazards models to identify factors associated with outcomes.ResultsWithin 6 months initiation of treatment with vedolizumab, significantly higher proportions of patients with early-stage CD, vs later-stage CD, achieved clinical remission (38% vs 23%), CSFR (43% vs 14%), and endoscopic remission (29% vs 13%) (P < .05 for all comparisons). After adjusting for disease-related factors including previous exposure to TNF antagonists, patients with early-stage CD were significantly more likely than patients with later-stage CD to achieve clinical remission (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.02-2.49), CSFR (aHR, 3.39; 95% CI, 1.66-6.92), and endoscopic remission (aHR, 1.90; 95% CI, 1.06-3.39). In contrast, disease duration was not a significant predictor of response among patients with UC.ConclusionsPatients with CD for 2 years or less are significantly more likely to achieve a complete response, CSFR, or endoscopic response to vedolizumab than patients with longer disease duration. Disease duration does not associate with response vedolizumab in patients with UC

Bridge study protocol: an international, observational cohort study on the transition of healthcare for adolescents with chronic conditions

IntroductionMore than 10% of adolescents live with a chronic disease or disability that requires regular medical follow-up as they mature into adulthood. During the first 2 years after adolescents with chronic conditions are transferred to adult hospitals, non-adherence rates approach 70% and emergency visits and hospitalisation rates significantly increase. The purpose of the Bridge study is to prospectively examine associations of transition readiness and care experiences with transition success: young patients’ health, health-related quality of life (HRQoL) and adherence to medical appointments as well as costs of care. In addition, we will track patients’ growing independence and educational and employment pathways during the transition process.Methods and analysisBridge is an international, prospective, observational cohort study. Study participants are adolescents with a chronic health condition or disability and their parents/guardians who attended the New Children’s Hospital in Helsinki, Finland, or the Royal Children’s Hospital (RCH) in Melbourne, Australia. Baseline assessment took place approximately 6 months prior to the transfer of care and follow-up data will be collected 1 year and 2 years after the transfer of care. Data will be collected from patients’ hospital records and from questionnaires completed by the patient and their parent/guardian at each time point. The primary outcomes of this study are adherence to medical appointments, clinical health status and HRQoL and costs of care. Secondary outcome measures are educational and employment outcomes.Ethics and disseminationThe Ethics Committee for Women’s and Children’s Health and Psychiatry at the Helsinki University Hospital (HUS/1547/2017) and the RCH Human Research Ethics Committee (38035) have approved the Bridge study protocol. Results will be published in international peer-reviewed journals and summaries will be provided to the funders of the study as well as patients and their parents/guardians.</p

Beyond factor analysis: Multidimensionality and the Parkinson’s Disease Sleep Scale-Revised

Many studies have sought to describe the relationship between sleep disturbance and cognition in Parkinson’s disease (PD). The Parkinson’s Disease Sleep Scale (PDSS) and its variants (the Parkinson’s disease Sleep Scale-Revised; PDSS-R, and the Parkinson’s Disease Sleep Scale-2; PDSS-2) quantify a range of symptoms impacting sleep in only 15 items. However, data from these scales may be problematic as included items have considerable conceptual breadth, and there may be overlap in the constructs assessed. Multidimensional measurement models, accounting for the tendency for items to measure multiple constructs, may be useful more accurately to model variance than traditional confirmatory factor analysis. In the present study, we tested the hypothesis that a multidimensional model (a bifactor model) is more appropriate than traditional factor analysis for data generated by these types of scales, using data collected using the PDSS-R as an exemplar. 166 participants diagnosed with idiopathic PD participated in this study. Using PDSS-R data, we compared three models: a unidimensional model; a 3-factor model consisting of sub-factors measuring insomnia, motor symptoms and obstructive sleep apnoea (OSA) and REM sleep behaviour disorder (RBD) symptoms; and, a confirmatory bifactor model with both a general factor and the same three sub-factors. Only the confirmatory bifactor model achieved satisfactory model fit, suggesting that PDSS-R data are multidimensional. There were differential associations between factor scores and patient characteristics, suggesting that some PDSS-R items, but not others, are influenced by mood and personality in addition to sleep symptoms. Multidimensional measurement models may also be a helpful tool in the PDSS and the PDSS-2 scales and may improve the sensitivity of these instruments

The hippocampus and entorhinal cortex encode the path and Euclidean distances to goals during navigation

BACKGROUND Despite decades of research on spatial memory, we know surprisingly little about how the brain guides navigation to goals. While some models argue that vectors are represented for navigational guidance, other models postulate that the future path is computed. Although the hippocampal formation has been implicated in processing spatial goal information, it remains unclear whether this region processes path- or vector-related information. RESULTS We report neuroimaging data collected from subjects navigating London's Soho district; these data reveal that both the path distance and the Euclidean distance to the goal are encoded by the medial temporal lobe during navigation. While activity in the posterior hippocampus was sensitive to the distance along the path, activity in the entorhinal cortex was correlated with the Euclidean distance component of a vector to the goal. During travel periods, posterior hippocampal activity increased as the path to the goal became longer, but at decision points, activity in this region increased as the path to the goal became closer and more direct. Importantly, sensitivity to the distance was abolished in these brain areas when travel was guided by external cues. CONCLUSIONS The results indicate that the hippocampal formation contains representations of both the Euclidean distance and the path distance to goals during navigation. These findings argue that the hippocampal formation houses a flexible guidance system that changes how it represents distance to the goal depending on the fluctuating demands of navigation

Human and mouse neuroinflammation markers in Niemann‐Pick disease, type C1

Niemann‐Pick disease, type C1 (NPC1) is an autosomal recessive lipid storage disorder in which a pathological cascade, including neuroinflammation occurs. While data demonstrating neuroinflammation is prevalent in mouse models, data from NPC1 patients is lacking. The current study focuses on identifying potential markers of neuroinflammation in NPC1 from both the Npc1 mouse model and NPC1 patients. We identified in the mouse model significant changes in expression of genes associated with inflammation and compared these results to the pattern of expression in human cortex and cerebellar tissue. From gene expression array analysis, complement 3 (C3) was increased in mouse and human post‐mortem NPC1 brain tissues. We also characterized protein levels of inflammatory markers in cerebrospinal fluid (CSF) from NPC1 patients and controls. We found increased levels of interleukin 3, chemokine (C‐X‐C motif) ligand 5, interleukin 16 and chemokine ligand 3 (CCL3), and decreased levels of interleukin 4, 10, 13 and 12p40 in CSF from NPC1 patients. CSF markers were evaluated with respect to phenotypic severity. Miglustat treatment in NPC1 patients slightly decreased IL‐3, IL‐10 and IL‐13 CSF levels; however, further studies are needed to establish a strong effect of miglustat on inflammation markers. The identification of inflammatory markers with altered levels in the cerebrospinal fluid of NPC1 patients may provide a means to follow secondary events in NPC1 disease during therapeutic trials.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147148/1/jimd0083.pd