DPVis: Visual Analytics with Hidden Markov Models for Disease Progression Pathways

Clinical researchers use disease progression models to understand patient status and characterize progression patterns from longitudinal health records. One approach for disease progression modeling is to describe patient status using a small number of states that represent distinctive distributions over a set of observed measures. Hidden Markov models (HMMs) and its variants are a class of models that both discover these states and make inferences of health states for patients. Despite the advantages of using the algorithms for discovering interesting patterns, it still remains challenging for medical experts to interpret model outputs, understand complex modeling parameters, and clinically make sense of the patterns. To tackle these problems, we conducted a design study with clinical scientists, statisticians, and visualization experts, with the goal to investigate disease progression pathways of chronic diseases, namely type 1 diabetes (T1D), Huntington's disease, Parkinson's disease, and chronic obstructive pulmonary disease (COPD). As a result, we introduce DPVis which seamlessly integrates model parameters and outcomes of HMMs into interpretable and interactive visualizations. In this study, we demonstrate that DPVis is successful in evaluating disease progression models, visually summarizing disease states, interactively exploring disease progression patterns, and building, analyzing, and comparing clinically relevant patient subgroups.Comment: to appear at IEEE Transactions on Visualization and Computer Graphic

The Parkinson's progression markers initiative (PPMI) - establishing a PD biomarker cohort.

ObjectiveThe Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials.MethodsA total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org.ResultsApproximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS-UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α-synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t-tau (45/53) and p-tau (16/18) were reduced in PD versus HC (P < 0.01).InterpretationPPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials

Arbeiten zur Optischen Kohärenztomographie, Magnetresonanzspektroskopie und Ultrahochfeld-Magnetresonanztomographie

Abstrakt (Deutsch) Hintergrund: Die Multiple Sklerose ist eine der häufigsten neurologischen Erkrankungen, die zu Behinderung bereits im jungen Erwachsenenalter führen kann. Hierzu tragen im Krankheitsprozess sowohl neuroinflammatorische wie auch neurodegenerative Komponenten bei. Moderne bildgebende Verfahren wie die Ultrahochfeld-Magnetresonanztomographie (UHF-MRT), die Optische Kohärenztomographie (OCT) und die Magnetresonanzspektroskopie (MRS) können benutzt werden, um diese neurodegenerativen Prozesse näher zu charakterisieren und im zeitlichen Verlauf zu beobachten. Zielsetzung: Ziel ist es, die genannten Verfahren zur Charakterisierung von Kohorten von MS-Patienten einzusetzen und die Verfahren zueinander, sowie mit klinischen Parametern in Beziehung zu setzen oder diagnostisch zu nutzen. Methodik: Patienten mit Multipler Sklerose oder Neuromyelitis optica wurden klinisch-neurologisch, mit Optischer Kohärenztomographie, Sehprüfungen, Untersuchungen der visuell evozierten Potentiale (VEP), (Ultrahochfeld-) Magnetresonanztomographie und Magnetresonanzspektroskopie untersucht. Ergebnisse: Die in der Studie eingesetzten bildgebenden Verfahren konnten dazu beitragen, Neuroinflammation und Neurodegeneration bei an Multiple Sklerose erkrankten Patienten näher zu charakterisieren. So steht eine mittels OCT messbare Verdünnung retinaler Nervenfaserschichten (RNFL) in Zusammenhang mit dem per MRT gemessenen Hirnparenchymvolumen und Neurodegeneration anzeigenden Parametern, die mithilfe der Magnetresonanzspektroskopie untersucht wurden. Mithilfe der UHF-MRT konnte ein Zusammenhang zwischen dem Volumen und der entzündlichen Läsionslast der Sehstrahlung, der RNFL-Dicke, VEP-Latenzen und Einschränkungen des Sehvermögens dargestellt werden. Außerdem ließen sich mit der UHF-MRT auch neurogenerative Aspekte im Sinne von bleibenden Parenchymdefekten innerhalb entzündlicher Läsionen und einer Verschmächtigung der Sehstrahlung nachweisen und die Detektion insbesondere kortikaler MS-Läsionen wurde im Vergleich zur konventionellen MRT verbessert. Zusammenfassung: OCT, MRS und UHF-MRT sind Verfahren, die eine genauere Beschreibung von Neuroinflammation und Neurodegeneration bei MS-Patienten ermöglichen, wie hier vor allem für die Sehbahn gezeigt wurde. Sie sind nichtinvasiv und lassen sich zur näheren Charakterisierung des aktuellen Zustandes und zur Beobachtung des Krankheitsverlaufs von MS-Patienten benutzen.Abstract (English) Background: Multiple sclerosis (MS) is the most common disabling neurologic disease, that causes impairment in younger people. Both neuroinflammatory and neurodegenerative processes contribute to the pathogenesis of multiple sclerosis. Innovative imaging methods, such as ultra-high field magnetic resonance tomography (UHF-MRI), optic coherence tomography (OCT) and magnetic resonance spectroscopy (MRS) can be used for characterizing these neurodegenerative processes in detail and over time course. Objective: To use the imaging methods mentioned above to further characterize cohorts of MS patients and to correlate the parameters with themselves as well as with clinical parameters and to evaluate their prognostic and diagnostic relevance. Methods: Patients with multiple sclerosis were examined clinically, by OCT, visual acuity testing, examination of visually evoked potentials, ultra high field magnetic resonance tomography and magnetic resonance spectroscopy. Results: The imaging methods used in these studies contributed to further characterize neuroinflammation und neurodegeneration in multiple sclerosis patients. A thinning of the retinal nerve fiber layer (RNFL) is correlated with brain parenchyma volume measured by MRI, and markers indicating ongoing neurodegenerative processes as detected by MRS. Using UHF-MRI, a correlation between optic radiation properties (such as inflammatory lesion load and its volume) and RNFL thickness, VEP latencies and visual impairment could be demonstrated. Furthermore, UHF-MRI demonstrated neurodegenerative aspects such as parenchymal defects within inflammatory lesions, an optic radiation thinning and allowed a more precise detection of MS lesions than conventional MRI, in particular cortical grey matter lesions. Summary: OCT, MRS and UHF-MRI are feasible methods to provide a more detailed description of neuroinflammation and neurodegeneration in MS patients, as demonstrated in these studies particularly for the visual pathway. They are non-invasive and can be utilized for clinical to study the disease course and also in differential diagnostic procedures

Cohort profile: the Siyakhula cohort, rural South Africa

No abstract available

Non-adherence to eye care in people with diabetes

Objective Evaluate individual factors that impact adherence to eye care follow-up in patients with diabetes. Design and methods A 4-year retrospective chart review was conducted for 1968 patients with diabetes over age 40 from an urban academic center. Data collected included demographics, insurance, visual acuity, smoking status, medications, dates of dilated fundus examinations (DFE), and reported hemoglobin A1C and blood glucose levels. The primary outcome was timely DFE follow-up adherence following the initial eye exam visit. Results Overall, 41.6% of patients adhered to initial follow-up eye care recommendations. Multivariable analysis demonstrated that patients with severe diabetic retinopathy (DR) were more adherent than patients with mild DR (OR 1.86). Other variables associated with increased adherence were visual impairment and reported A1C or blood glucose. Smoking was associated with decreased adherence. Ethnicity and insurance were also significantly associated with adherence. Longitudinal follow-up rates were influenced by additional factors, including ethnicity and neighborhood deprivation index. Conclusions Patients with moderate to severe DR and/ or visual impairment were more likely to adhere to timely DFE follow-up. This could relate to the presence of visual symptoms and/or other systemic manifestations of diabetes. Smokers were less likely to adhere to timely DFE follow-up. One hypothesis is patients who smoke have other symptomatic health problems which patients prioritize over asymptomatic ocular disorders. In order to reduce vision loss from DR, practitioners should be aware that patients with mild and moderate DR, patients with normal vision, and smokers are at greater risk for poor follow-up eye care adherence. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved

Visual Perceptual Difficulties and Under-Achievement at School in a Large Community-Based Sample of Children

Difficulties with visual perception (VP) are often described in children with neurological or developmental problems. However, there are few data regarding the range of visual perceptual abilities in populations of normal children, or on the impact of these abilities on children's day-to-day functioning. Methods Data were obtained for 4512 participants in an ongoing birth cohort study (Avon Longitudinal Study of Parents and Children; ALSPAC). The children's mothers responded to questions designed to elicit indications of visual perceptual difficulties or immaturity, when their children were aged 13 years. We examined associations with standardised school test results in reading and in mathematics at age 1314 years (SATS-KS3), accounting for potential confounders including IQ. Results Three underlying factors explained half the variance in the VP question responses. These correlated best with questions on interpreting cluttered scenes; guidance of movement and face recognition. The adjusted parameter estimates (95% CI) for the cluttered-scenes factor (0.05; 0.02 to 0.08; p<0.001) suggested positive associations with the reading test results whilst that for the guidance-of-movement factor (0.03; 0.00 to 0.06; p = 0.026) suggested positive association with the mathematics results. The raw scores were associated with both test results. Discussion VP abilities were widely distributed in this sample of 13-year old children. Lower levels of VP function were associated with under-achievement in reading and in mathematics. Simple interventions can help children with VP difficulties, so research is needed into practicable, cost-effective strategies for identification and assessment, so that support can be targeted appropriately

Chronic Post-Concussion Neurocognitive Deficits. I. Relationship with White Matter Integrity.

We previously identified visual tracking deficits and associated degradation of integrity in specific white matter tracts as characteristics of concussion. We re-explored these characteristics in adult patients with persistent post-concussive symptoms using independent new data acquired during 2009-2012. Thirty-two patients and 126 normal controls underwent cognitive assessments and MR-DTI. After data collection, a subset of control subjects was selected to be individually paired with patients based on gender and age. We identified patients' cognitive deficits through pairwise comparisons between patients and matched control subjects. Within the remaining 94 normal subjects, we identified white matter tracts whose integrity correlated with metrics that indicated performance degradation in patients. We then tested for reduced integrity in these white matter tracts in patients relative to matched controls. Most patients showed no abnormality in MR images unlike the previous study. Patients' visual tracking was generally normal. Patients' response times in an attention task were slowed, but could not be explained as reduced integrity of white matter tracts relating to normal response timing. In the present patient cohort, we did not observe behavioral or anatomical deficits that we previously identified as characteristic of concussion. The recent cohort likely represented those with milder injury compared to the earlier cohort. The discrepancy may be explained by a change in the patient recruitment pool circa 2007 associated with an increase in public awareness of concussion

Maternal thyroid function and child educational attainment: prospective cohort study

Objective: To determine if first trimester maternal thyroid dysfunction is a critical determinant of child scholastic performance and overall educational attainment. Design: Prospective cohort study. Setting: Avon Longitudinal Study of Parents and Children cohort in the UK. Participants: 4615 mother-child pairs with an available first trimester sample (median 10 weeks gestation, interquartile range 8-12). Exposures: Free thyroxine, thyroid stimulating hormone, and thyroid peroxidase antibodies assessed as continuous measures and the seven clinical categories of maternal thyroid function. Main outcome measures: Five age-specific national curriculum assessments in 3580 children at entry stage assessment at 54 months, increasing up to 4461 children at their final school assessment at age 15. Results: No strong evidence of clinically meaningful associations of first trimester free thyroxine and thyroid stimulating hormone levels with entry stage assessment score or Standard Assessment Test scores at any of the key stages was found. Associations of maternal free thyroxine or thyroid stimulating hormone with the total number of General Certificates of Secondary Education (GCSEs) passed (range 0-16) were all close to the null: free thyroxine, rate ratio per pmol/L 1.00 (95% confidence interval 1.00 to 1.01); and thyroid stimulating hormone, rate ratio 0.98 (0.94 to 1.02). No important relationship was observed when more detailed capped scores of GCSEs allowing for both the number and grade of pass or when language, mathematics, and science performance were examined individually or when all educational assessments undertaken by an individual from school entry to leaving were considered. 200 (4.3%) mothers were newly identified as having hypothyroidism or subclinical hypothyroidism and 97 (2.1%) subclinical hyperthyroidism or hyperthyroidism. Children of mothers with thyroid dysfunction attained an equivalent number of GCSEs and equivalent grades as children of mothers with euthyroidism. Conclusions: Maternal thyroid dysfunction in early pregnancy does not have a clinically important association with impaired child performance at school or educational achievement