195 research outputs found
Association of EP2 receptor and SLC19A3 in regulating breast cancer metastasis
published_or_final_versio
Communicating with mismatch and tension: treatment provision experiences of primary care doctors treating patients with overactive bladder in Hong Kong
Outcome Measures for Disease-Modifying Trials in Parkinson\u27s Disease: Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative
\ua9 2023-The authors. Published by IOS Press.Background: Multi-Arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson\u27s disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach. Objective: To provide an up-To-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials. Methods: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives\u27 input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory. Results: An extensive inventory of OM was created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages. Conclusion: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges
Neurogenesis Drives Stimulus Decorrelation in a Model of the Olfactory Bulb
The reshaping and decorrelation of similar activity patterns by neuronal
networks can enhance their discriminability, storage, and retrieval. How can
such networks learn to decorrelate new complex patterns, as they arise in the
olfactory system? Using a computational network model for the dominant neural
populations of the olfactory bulb we show that fundamental aspects of the adult
neurogenesis observed in the olfactory bulb -- the persistent addition of new
inhibitory granule cells to the network, their activity-dependent survival, and
the reciprocal character of their synapses with the principal mitral cells --
are sufficient to restructure the network and to alter its encoding of odor
stimuli adaptively so as to reduce the correlations between the bulbar
representations of similar stimuli. The decorrelation is quite robust with
respect to various types of perturbations of the reciprocity. The model
parsimoniously captures the experimentally observed role of neurogenesis in
perceptual learning and the enhanced response of young granule cells to novel
stimuli. Moreover, it makes specific predictions for the type of odor
enrichment that should be effective in enhancing the ability of animals to
discriminate similar odor mixtures
Embedding Patient Input in Outcome Measures for Long-Term Disease-Modifying Parkinson Disease Trials
BACKGROUND: Clinical trials of disease-modifying therapies in PD require valid and responsive primary outcome measures that are relevant to patients. OBJECTIVES: The objective is to select a patient-centered primary outcome measure for disease-modification trials over three or more years. METHODS: Experts in Parkinson's disease (PD), statistics, and health economics and patient and public involvement and engagement (PPIE) representatives reviewed and discussed potential outcome measures. A larger PPIE group provided input on their key considerations for such an endpoint. Feasibility, clinimetric properties, and relevance to patients were assessed and synthesized. RESULTS: Although initial considerations favored the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in Off, feasibility, PPIE input, and clinimetric properties supported the MDS-UPDRS Part II. However, PPIE input also highlighted the importance of nonmotor symptoms, especially in the longer term, leading to the selection of the MDS-UPDRS Parts I + II sum score. CONCLUSIONS: The MDS-UPDRS Parts I + II sum score was chosen as the primary outcome for large 3-year disease-modification trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Association between knee alignment and knee pain in patients surgically treated for medial knee osteoarthritis by high tibial osteotomy. A one year follow-up study
<p>Abstract</p> <p>Background</p> <p>The association between knee alignment and knee pain in knee osteoarthritis (OA) is unclear. High tibial osteotomy, a treatment option in knee OA, alters load from the affected to the unaffected compartment of the knee by correcting malalignment. This surgical procedure thus offers the possibility to study the cross-sectional and longitudinal association of alignment to pain. The aims were to study 1) the preoperative association of knee alignment to preoperative knee pain and 2) the association of change in knee alignment with surgery to change in knee pain over time in patients operated on for knee OA by high tibial osteotomy.</p> <p>Methods</p> <p>182 patients (68% men) mean age 53 years (34 - 69) with varus alignment having tibial osteotomy by the hemicallotasis technique for medial knee OA were consecutively included. Knee alignment was assessed by the Hip-Knee-Ankle (HKA) angle from radiographs including the hip and ankle joints. Knee pain was measured by the subscale pain (0 - 100, worst to best scale) of the Knee injury and Osteoarthritis Outcome Score (KOOS) preoperatively and at one year follow-up. To estimate the association between knee alignment and knee pain multivariate regression analyses were used.</p> <p>Results</p> <p>Mean preoperative varus alignment was 170 degrees (153 - 178) and mean preoperative KOOS pain was 42 points (3 - 86). There was no association between preoperative varus alignment and preoperative KOOS pain, crude analysis 0.02 points (95% CI -0.6 - 0.7) change in pain with every degree of HKA angle, adjusted analysis 0.3 points (95% CI -1.3 - 0.6).</p> <p>The mean postoperative knee alignment was 184 degrees (171 - 185). The mean change in knee alignment was 13 degrees (0 - 30). The mean change in KOOS pain was 32 (-16 - 83). There was neither any association between change in knee alignment and change in KOOS pain over time, crude analysis 0.3 point (95% CI -0.6 - 1.2), adjusted analysis 0.4 points (95% CI 0.6 - 1.4).</p> <p>Conclusion</p> <p>We found no association between knee alignment and knee pain in patients with knee OA indicating that alignment and pain are separate entities, and that the degree of preoperative malalignment is not a predictor of knee pain after high tibial osteotomy.</p
Indicated prevention interventions for anxiety in children and adolescents: a review and meta-analysis of school-based programs
Anxiety disorders are among the most common youth mental health disorders. Early intervention can reduce elevated anxiety symptoms. School-based interventions exist but it is unclear how effective targeted approaches are for reducing symptoms of anxiety. This review and meta-analysis aimed to determine the effectiveness of school-based indicated interventions for symptomatic children and adolescents. The study was registered with PROSPERO [CRD42018087628]. We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Library for randomised-controlled trials comparing indicated programs for child and adolescent (5–18 years) anxiety to active or inactive control groups. Data were extracted from papers up to December 2019. The primary outcome was efficacy (mean change in anxiety symptom scores). Sub-group and sensitivity analyses explored intervention intensity and control type. We identified 20 studies with 2076 participants. Eighteen studies were suitable for meta-analysis. A small positive effect was found for indicated programs compared to controls on self-reported anxiety symptoms at post-test (g = − 0.28, CI = − 0.50, − 0.05, k = 18). This benefit was maintained at 6 (g = − 0.35, CI = − 0.58, − 0.13, k = 9) and 12 months (g = − 0.24, CI = − 0.48, 0.00, k = 4). Based on two studies, > 12 month effects were very small (g = − 0.01, CI = − 0.38, 0.36). No differences were found based on intervention intensity or control type. Risk of bias and variability between studies was high (I2 = 78%). Findings show that school-based indicated programs for child and adolescent anxiety can produce small beneficial effects, enduring for up to 12 months. Future studies should include long-term diagnostic assessments
Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set
We report a measurement of the bottom-strange meson mixing phase \beta_s
using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays
in which the quark-flavor content of the bottom-strange meson is identified at
production. This measurement uses the full data set of proton-antiproton
collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment
at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity.
We report confidence regions in the two-dimensional space of \beta_s and the
B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2,
-1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in
agreement with the standard model expectation. Assuming the standard model
value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +-
0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +-
0.009 (syst) ps, which are consistent and competitive with determinations by
other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
Recent trends in chronic disease, impairment and disability among older adults in the United States
<p>Abstract</p> <p>Background</p> <p>To examine concurrent prevalence trends of chronic disease, impairment and disability among older adults.</p> <p>Methods</p> <p>We analyzed the 1998, 2004 and 2008 waves of the Health and Retirement Study, a nationally representative survey of older adults in the United States, and included 31,568 community dwelling adults aged 65 and over. Measurements include: prevalence of chronic diseases including hypertension, heart disease, stroke, diabetes, cancer, chronic lung disease and arthritis; prevalence of impairments, including impairments of cognition, vision, hearing, mobility, and urinary incontinence; prevalence of disability, including activities of daily living (ADLs) and instrumental activities of daily living (IADLs).</p> <p>Results</p> <p>The proportion of older adults reporting no chronic disease decreased from 13.1% (95% Confidence Interval [CI], 12.4%-13.8%) in 1998 to 7.8% (95% CI, 7.2%-8.4%) in 2008, whereas the proportion reporting 1 or more chronic diseases increased from 86.9% (95% CI, 86.2%-89.6%) in 1998 to 92.2% (95% CI, 91.6%-92.8%) in 2008. In addition, the proportion reporting 4 or more diseases increased from 11.7% (95% CI, 11.0%-12.4%) in 1998 to 17.4% (95% CI, 16.6%-18.2%) in 2008. The proportion of older adults reporting no impairments was 47.3% (95% CI, 46.3%-48.4%) in 1998 and 44.4% (95% CI, 43.3%-45.5%) in 2008, whereas the proportion of respondents reporting 3 or more was 7.2% (95% CI, 6.7%-7.7%) in 1998 and 7.3% (95% CI, 6.8%-7.9%) in 2008. The proportion of older adults reporting any ADL or IADL disability was 26.3% (95% CI, 25.4%-27.2%) in 1998 and 25.4% (95% CI, 24.5%-26.3%) in 2008.</p> <p>Conclusions</p> <p>Multiple chronic disease is increasingly prevalent among older U.S. adults, whereas the prevalence of impairment and disability, while substantial, remain stable.</p
Gait stability and variability measures show effects of impaired cognition and dual tasking in frail people
<p>Abstract</p> <p>Background</p> <p>Falls in frail elderly are a common problem with a rising incidence. Gait and postural instability are major risk factors for falling, particularly in geriatric patients. As walking requires attention, cognitive impairments are likely to contribute to an increased fall risk. An objective quantification of gait and balance ability is required to identify persons with a high tendency to fall. Recent studies have shown that stride variability is increased in elderly and under dual task condition and might be more sensitive to detect fall risk than walking speed. In the present study we complemented stride related measures with measures that quantify trunk movement patterns as indicators of dynamic balance ability during walking. The aim of the study was to quantify the effect of impaired cognition and dual tasking on gait variability and stability in geriatric patients.</p> <p>Methods</p> <p>Thirteen elderly with dementia (mean age: 82.6 ± 4.3 years) and thirteen without dementia (79.4 ± 5.55) recruited from a geriatric day clinic, walked at self-selected speed with and without performing a verbal dual task. The Mini Mental State Examination and the Seven Minute Screen were administered. Trunk accelerations were measured with an accelerometer. In addition to walking speed, mean, and variability of stride times, gait stability was quantified using stochastic dynamical measures, namely regularity (sample entropy, long range correlations) and local stability exponents of trunk accelerations.</p> <p>Results</p> <p>Dual tasking significantly (p < 0.05) decreased walking speed, while stride time variability increased, and stability and regularity of lateral trunk accelerations decreased. Cognitively impaired elderly showed significantly (p < 0.05) more changes in gait variability than cognitive intact elderly. Differences in dynamic parameters between groups were more discerned under dual task conditions.</p> <p>Conclusions</p> <p>The observed trunk adaptations were a consistent instability factor. These results support the concept that changes in cognitive functions contribute to changes in the variability and stability of the gait pattern. Walking under dual task conditions and quantifying gait using dynamical parameters can improve detecting walking disorders and might help to identify those elderly who are able to adapt walking ability and those who are not and thus are at greater risk for falling.</p
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