scholarly journals Mapping cortical disease-burden at individual-level in frontotemporal dementia: implications for clinical care and pharmacological trials

Author(s):  
Mary Clare McKenna ◽  
Marlene Tahedl ◽  
Jasmin Lope ◽  
Rangariroyashe H. Chipika ◽  
Stacey Li Hi Shing ◽  
...  

AbstractImaging studies of FTD typically present group-level statistics between large cohorts of genetically, molecularly or clinically stratified patients. Group-level statistics are indispensable to appraise unifying radiological traits and describe genotype-associated signatures in academic studies. However, in a clinical setting, the primary objective is the meaningful interpretation of imaging data from individual patients to assist diagnostic classification, inform prognosis, and enable the assessment of progressive changes compared to baseline scans. In an attempt to address the pragmatic demands of clinical imaging, a prospective computational neuroimaging study was undertaken in a cohort of patients across the spectrum of FTD phenotypes. Cortical changes were evaluated in a dual pipeline, using standard cortical thickness analyses and an individualised, z-score based approach to characterise subject-level disease burden. Phenotype-specific patterns of cortical atrophy were readily detected with both methodological approaches. Consistent with their clinical profiles, patients with bvFTD exhibited orbitofrontal, cingulate and dorsolateral prefrontal atrophy. Patients with ALS-FTD displayed precentral gyrus involvement, nfvPPA patients showed widespread cortical degeneration including insular and opercular regions and patients with svPPA exhibited relatively focal anterior temporal lobe atrophy. Cortical atrophy patterns were reliably detected in single individuals, and these maps were consistent with the clinical categorisation. Our preliminary data indicate that standard T1-weighted structural data from single patients may be utilised to generate maps of cortical atrophy. While the computational interpretation of single scans is challenging, it offers unrivalled insights compared to visual inspection. The quantitative evaluation of individual MRI data may aid diagnostic classification, clinical decision making, and assessing longitudinal changes.

2016 ◽  
Vol 3 (2) ◽  
pp. e26 ◽  
Author(s):  
Deborah J Cohen ◽  
Sara R Keller ◽  
Gillian R Hayes ◽  
David A Dorr ◽  
Joan S Ash ◽  
...  

2021 ◽  
Vol 15 ◽  
Author(s):  
Sahin Hanalioglu ◽  
Siyar Bahadir ◽  
Ilkay Isikay ◽  
Pinar Celtikci ◽  
Emrah Celtikci ◽  
...  

Objective: Graph theory applications are commonly used in connectomics research to better understand connectivity architecture and characterize its role in cognition, behavior and disease conditions. One of the numerous open questions in the field is how to represent inter-individual differences with graph theoretical methods to make inferences for the population. Here, we proposed and tested a simple intuitive method that is based on finding the correlation between the rank-ordering of nodes within each connectome with respect to a given metric to quantify the differences/similarities between different connectomes.Methods: We used the diffusion imaging data of the entire HCP-1065 dataset of the Human Connectome Project (HCP) (n = 1,065 subjects). A customized cortical subparcellation of HCP-MMP atlas (360 parcels) (yielding a total of 1,598 ROIs) was used to generate connectivity matrices. Six graph measures including degree, strength, coreness, betweenness, closeness, and an overall “hubness” measure combining all five were studied. Group-level ranking-based aggregation method (“measure-then-aggregate”) was used to investigate network properties on population level.Results: Measure-then-aggregate technique was shown to represent population better than commonly used aggregate-then-measure technique (overall rs: 0.7 vs 0.5). Hubness measure was shown to highly correlate with all five graph measures (rs: 0.88–0.99). Minimum sample size required for optimal representation of population was found to be 50 to 100 subjects. Network analysis revealed a widely distributed set of cortical hubs on both hemispheres. Although highly-connected hub clusters had similar distribution between two hemispheres, average ranking values of homologous parcels of two hemispheres were significantly different in 71% of all cortical parcels on group-level.Conclusion: In this study, we provided experimental evidence for the robustness, limits and applicability of a novel group-level ranking-based hubness analysis technique. Graph-based analysis of large HCP dataset using this new technique revealed striking hemispheric asymmetry and intraparcel heterogeneities in the structural connectivity of the human brain.


Data in Brief ◽  
2021 ◽  
pp. 107484
Author(s):  
Marlene Tahedl ◽  
Stacey Li Hi Shing ◽  
Eoin Finegan ◽  
Rangariroyashe H. Chipika ◽  
Jasmin Lope ◽  
...  

2021 ◽  
Vol 4 (2) ◽  
Author(s):  
Géza Kogler ◽  
Christopher Hovorka

This position paper outlines the important role of academia in shaping the orthotics and prosthetics (O&P) profession and preparing for its future. In the United States, most healthcare professions including O&P are under intense pressure to provide cost effective treatments and quantifiable health outcomes. Pivotal changes are needed in the way O&P services are provided to remain competitive. This will require the integration of new technologies and data driven processes that have the potential to streamline workflows, reduce errors and inform new methods of clinical care and device manufacturing. Academia can lead this change, starting with a restructuring in academic program curricula that will enable the next generation of professionals to cope with multiple demands such as the provision of services for an increasing number of patients by a relatively small workforce of certified practitioners delivering these services at a reduced cost, with the expectation of significant, meaningful, and measurable value. Key curricular changes will require replacing traditional labor-intensive and inefficient fabrication methods with the integration of newer technologies (i.e., digital shape capture, digital modeling/rectification and additive manufacturing). Improving manufacturing efficiencies will allow greater curricular emphasis on clinical training and education – an area that has traditionally been underemphasized. Providing more curricular emphasis on holistic patient care approaches that utilize systematic and evidence-based methods in patient assessment, treatment planning, dosage of O&P technology use, and measurement of patient outcomes is imminent. Strengthening O&P professionals’ clinical decision-making skills and decreasing labor-intensive technical fabrication aspects of the curriculum will be critical in moving toward a digital and technology-centric practice model that will enable future practitioners to adapt and survive. Article PDF Link: https://jps.library.utoronto.ca/index.php/cpoj/article/view/36673/28349 How To Cite: Kogler GF, Hovorka CF. Academia’s role to drive change in the orthotics and prosthetics profession. Canadian Prosthetics & Orthotics Journal. 2021; Volume 4, Issue 2, No.21. https://doi.org/10.33137/cpoj.v4i2.36673 Corresponding Author: Géza F. KoglerOrthotics and Prosthetics Unit, Kennesaw State University.E-Mail: [email protected] ID: https://orcid.org/0000-0003-0212-5520


2013 ◽  
Vol 2013 ◽  
pp. 1-6
Author(s):  
Kelly Gebo ◽  
Cindy Voss ◽  
Joseph Mrus ◽  
HIV Research Network

This observational analysis examined the clinical outcomes of patients receiving etravirine-(ETR-) based therapy, particularly with protease inhibitors (PIs) other than darunavir (DRV) and with raltegravir (RAL). Data included treatment-experienced adults in the HIV Research Network who began ETR-containing antiretroviral regimens in 2008–2010. The primary objective was to assess 6-month outcomes (durability, i.e., still on an ETR-containing regimen; change in CD4+ cell count and HIV-1 RNA <400 copies/mL). The cohort included 587 patients receiving ETR; 42% of ETR use was in patients not on DRV/ritonavir (r). Patients receiving ETR plus DRV/r had longer durability versus those on ETR plus a PI other than DRV/r at months 6 (91.2% versus 85.5%) and 12 (77.4% versus 65.2%), respectively. Patients on regimens with a PI other than DRV/r were the least likely to be receiving ETR at month 6 (85.5%) versus patients on other ETR-based regimens. Patients on regimens without a PI and without RAL had lower virologic suppression (month 6, 54.2%; month 12, 63.2%) versus patients on other ETR-based regimens. In a clinical care, nontrial setting, ETR was used in regimens without DRV/r. In this population, the 6-month response rates were similar and durable across all regimens, except when ETR was used without RAL and without a PI.


2021 ◽  
Author(s):  
Rebeca Mozun ◽  
Cristina Ardura-Garcia ◽  
Eva S. L. Pedersen ◽  
Jakob Usemann ◽  
Florian Singer ◽  
...  

AbstractBackgroundReferences from the Global Lung Function Initiative (GLI) are widely used to interpret children’s spirometry results. We assessed fit for healthy schoolchildren.MethodsLuftiBus in the school (LUIS) is a population-based cross-sectional study done from 2013-2016 in the canton of Zurich, Switzerland. Parents and children aged 6-17 years answered questionnaires about respiratory symptoms and lifestyle. Children underwent spirometry in a mobile lung function lab. We calculated GLI-based z-scores for FEV1, FVC, FEV1/FVC, and FEF25-75 for healthy White participants. We defined appropriate fit to GLI references by mean values ±0.5 z-scores. We assessed if fit varied by age, body mass index, height, and sex using linear regression models.ResultsWe analysed data from 2036 children with valid FEV1 measurements of which 1762 also had valid FVC measurements. The median age was 12.2 years. Fit was appropriate for children aged 6-11 years for all indices. In adolescents aged 12-17 years, fit was appropriate for FEV1/FVC (mean: -0.09; SD: 1.02) z-scores, but not for FEV1 (mean: -0.62; SD: 0.98), FVC (mean: -0.60; SD: 0.98), and FEF25-75 (mean: -0.54; SD: 1.02). FEV1, FVC, and FEF25-75 z-scores fitted better in children considered overweight (means: -0.25, -0.13, -0.38) than normal weight (means: -0.55, -0.50, -0.55; p-trend: <0.001, 0.014, <0.001). FEV1, FVC, and FEF25-75 z-scores depended on both age and height (p interaction: 0.034, 0.019, <0.01).ConclusionGLI-based FEV1, FVC, and FEF25-75 z-scores do not fit White Swiss adolescents well. This should be considered when using reference equations for clinical decision making, research and international comparison.Take home messageOur study suggests GLI-based FEV1, FVC, and FEF25-75 z-scores over detect abnormal lung function in Swiss adolescents, and more so among slimmer adolescents, which has important implications for clinical care, research, and international comparisons.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012975
Author(s):  
Wyatt P. Bensken ◽  
Guadalupe Fernandez-Baca Vaca ◽  
Barbara C. Jobst ◽  
Scott M. Williams ◽  
Kurt C. Stange ◽  
...  

Objective:People with epilepsy, one-third of whom in the US are on Medicaid, experience a wide range of chronic and physical comorbidities that influence their care and outcomes. In this study, we examine the burden and racial/ethnic disparities of chronic and acute conditions, injuries, and symptoms in a large and diverse group of people with epilepsy on Medicaid.Methods:Using 5 years of Medicaid claims data we identified adult people with epilepsy and used all available claims and diagnoses to identify each person’s Clinical Classification Codes groups diagnosed during the study period. Using association rule mining we identified the top combinations of conditions and stratified these by race/ethnicity to identify potential prevalence disparities. Additionally, we examined the top combinations of conditions in high utilizers – that is individuals in the top quartile of hospitalizations and emergency department visits.Results:Among 81,963 patients the most common conditions were: anxiety and mood disorders (46.5%), hypertension (36.9%), back problems (35.2%), developmental disorders (31.6%), and headache (29.5%). When examining combinations of conditions, anxiety and mood disorders continued to have an outsized prevalence – appearing in nearly every combination. There were notable disparities in disease burden, with American Indians and Alaskan Natives having a substantially higher prevalence of developmental disabilities, while Black individuals had a higher prevalence of hypertension. These disparities persisted to the higher-order combinations that included these conditions. High utilizers had a much higher disease burden, with 75.8% having an anxiety or mood disorder, as well as a higher burden of injuries.Significance:This study shows a high prevalence of psychiatric and physical conditions and identifies racial and ethnic disparities affecting people with epilepsy. Targeting interventions to consider the comorbidities, race and ethnicity has potential to improve clinical care and reduce disparities.


2018 ◽  
Vol 84 (10) ◽  
pp. 1670-1674 ◽  
Author(s):  
Yiping Li ◽  
Talar Tejirian ◽  
J. Craig Collins

The finding of gallbladder polyps on imaging studies prompts further workup. Imaging results are often discordant with final pathology. The goal of this study is to compare polypoid lesions of the gallbladder found on preoperative ultrasound (US) with final pathologic diagnosis after cholecystectomy to help guide clinical decision-making. A retrospective study was conducted identifying adult patients who were diagnosed with polyps via US and who underwent cholecystectomy from 2008 through 2015. Imaging data, final pathology, and demographics were manually reviewed. A total of 2290 cholecystectomy patients had US-based polyps. Of these, 1661 patients (73%) did not have polyps on final pathology; primarily, stones or sludge were identified. Adenomyosis was diagnosed in 61 patients (2.7%). A total of 556 patients (24.2%) had pathologic polypoid lesions with the following breakdown: 463 (20.2%) cholesterol polyps, 43 other benign polyps (1.8%), 40 adenomas (1.7%), and 10 adenocarcinomas (0.4%). All patients with adenocarcinoma were older than 40 years and 91 per cent had US findings of polyps >10 mm. Ultrasound alone is an unreliable method of detecting real gallbladder polyps. This large database study found a very low risk of cancer. Size on US and patient age should be considered in the selection of appropriate surgical candidates with sonographic “polyps.”


BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e033923
Author(s):  
Kieran Mccafferty ◽  
Ben Caplin ◽  
Sinead Knight ◽  
Paul Hockings ◽  
David Wheeler ◽  
...  

IntroductionDiabetic kidney disease (DKD) is the leading cause of end-stage kidney disease worldwide and a major cause of premature mortality in diabetes mellitus (DM). While improvements in care have reduced the incidence of kidney disease among those with DM, the increasing prevalence of DM means that the number of patients worldwide with DKD is increasing. Improved understanding of the biology of DKD and identification of novel therapeutic targets may lead to new treatments. A major challenge to progress has been the heterogeneity of the DKD phenotype and renal progression. To investigate the heterogeneity of DKD we have set up The East and North London Diabetes Cohort (HEROIC) Study, a secondary care-based, multiethnic observational study of patients with biopsy-proven DKD. Our primary objective is to identify histological features of DKD associated with kidney endpoints in a cohort of patients diagnosed with type 1 and type 2 DM, proteinuria and kidney impairment.Methods and analysisHEROIC is a longitudinal observational study that aims to recruit 500 patients with DKD at high-risk of renal and cardiovascular events. Demographic, clinical and laboratory data will be collected and assessed annually for 5 years. Renal biopsy tissue will be collected and archived at recruitment. Blood and urine samples will be collected at baseline and during annual follow-up visits. Measured glomerular filtration rate (GFR), echocardiography, retinal optical coherence tomography angiography and kidney and cardiac MRI will be performed at baseline and twice more during follow-up. The study is 90% powered to detect an association between key histological and imaging parameters and a composite of death, renal replacement therapy or a 30% decline in estimated GFR.Ethics and disseminationEthical approval has been obtained from the Bloomsbury Research Ethics Committee (REC 18-LO-1921). Any patient identifiable data will be stored on a password-protected National Health Services N3 network with full audit trail. Anonymised imaging data will be stored in a ISO27001-certificated data warehouse.Results will be reported through peer-reviewed manuscripts and conferences and disseminated to participants, patients and the public using web-based and social media engagement tools as well as through public events.


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