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BACKGROUND: Apical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19. OBJECTIVE: To prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients. METHODS: In this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed. RESULTS: CTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8-95.2) and negative predictive value (NPV; 97.8 %, 96.5-98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8-95.5; NPV 99.7 %, 98.3-100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2-40.1), myalgia (8.9, 2.1-38.2) and higher core body temperature (1.9, 1.1-3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality. CONCLUSION: Apical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.
Subject(s)
COVID-19 , Computed Tomography Angiography , Stroke , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Biomarkers , Computed Tomography Angiography/methods , COVID-19/diagnostic imaging , Lung/diagnostic imaging , Prognosis , Prospective Studies , SARS-CoV-2 , Stroke/diagnostic imagingABSTRACT
Introduction: Health workers faced overwhelming demands and experienced crisis levels of burnout before the COVID-19 pandemic; the pandemic presented unique challenges that further impaired their mental health. Methods: Data from the General Social Survey Quality of Worklife Module were analyzed to compare self-reported mental health symptoms among U.S. adult workers from 2018 (1,443 respondents, including 226 health workers) and 2022 (1,952, including 325 health workers). Logistic regression was used to examine associations between health workers' reported perceptions of working conditions and anxiety, depression, and burnout. Results: From 2018 to 2022, health workers reported an increase of 1.2 days of poor mental health during the previous 30 days (from 3.3 days to 4.5 days); the percentage who reported feeling burnout very often (11.6% to 19.0%) increased. In 2022, health workers experienced a decrease in odds of burnout if they trusted management (odds ratio [OR] = 0.40), had supervisor help (OR = 0.26), had enough time to complete work (OR = 0.33), and felt that their workplace supported productivity (OR = 0.38), compared with those who did not. Harassment at work was associated with increased odds of anxiety (OR = 5.01), depression (OR = 3.38), and burnout (OR = 5.83). Conclusions and implications for public health practice: Health workers continued to face a mental health crisis in 2022. Positive working conditions were associated with less burnout and better mental health. CDC's National Institute for Occupational Safety and Health has developed a national campaign, Impact Wellbeing, to provide employers of health workers with resources to improve the mental health of these workers.
Subject(s)
Burnout, Professional , Mental Health , Adult , Humans , United States/epidemiology , Working Conditions , Pandemics , Health Personnel/psychology , Burnout, Professional/epidemiology , Burnout, Professional/psychology , Surveys and Questionnaires , Vital SignsABSTRACT
Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men. Localised PCa can be treated effectively, but most patients relapse/progress to more aggressive disease. One possible mechanism underlying this progression is alternative splicing of the androgen receptor, with AR variant 7(ARV7) considered to play a major role. Using viability assays, we confirmed that ARV7-positive PCa cells were less sensitive to treatment with cabazitaxel and an anti-androgen-enzalutamide. Also, using live-holographic imaging, we showed that PCa cells with ARV7 exhibited an increased rate of cell division, proliferation, and motility, which could potentially contribute to a more aggressive phenotype. Furthermore, protein analysis demonstrated that ARV7 knock-down was associated with a decrease in insulin-like growth factor-2 (IGFBP-2) and forkhead box protein A1(FOXA1). This correlation was confirmed in-vivo using PCa tissue samples. Spearman rank correlation analysis showed significant positive associations between ARV7 and IGFBP-2 or FOXA1 in tissue from patients with PCa. This association was not present with the AR. These data suggest an interplay of FOXA1 and IGFBP-2 with ARV7-mediated acquisition of an aggressive prostate cancer phenotype.
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PURPOSE: Cortical visual impairment (CVI) is the most common cause of visual impairment in children today and can impact the outcomes of children who rely on augmentative and alternative communication (AAC). This study provides baseline data of 13 children with CVI who used AAC during their first year of participation in an integrated CVI program. One purpose was to describe similarities and differences in the student's demographic, functional vision, communication, and educational profiles. A second purpose was to examine differences in students described with different communicator profiles. METHOD: Archived student records were de-identified and reviewed using a systematic coding scheme. Two researchers independently reviewed and coded all student records. Reliability was established. Measures included CVI Range scores; supports for positioning, mobility, vision, and writing; AAC systems, including modes, access methods, and language representation; communicative competence; self-determination; literacy; and mathematics. RESULTS: The study yielded a rich description of similarities and differences among students at baseline and led to careful consideration of differences among the participants with emergent communicator and context-dependent communicator profiles. CONCLUSIONS: Currently, limited evidence exists that informs practice regarding AAC assessment and intervention for children with CVI. This article describes a small sample of children with CVI who use AAC. Results underscore the need for educators and practitioners to ensure that vision functioning in students with CVI is evaluated carefully and regularly when conducting AAC assessment and intervention and formulating communication or education goals. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21357684.
Subject(s)
Communication Aids for Disabled , Communication Disorders , Vision Disorders , Child , Humans , Communication , Communication Disorders/complications , Communication Disorders/therapy , Reproducibility of Results , Retrospective Studies , Vision Disorders/complications , Vision Disorders/therapyABSTRACT
PURPOSE: Recovering from stroke in remote Australia has rarely been considered, even though rehabilitation services are generally scarce. The primary purpose of this study was to explore stroke recovery, from the perspective of stroke survivors in remote northwest Queensland (NWQ), to explicate the lens through which they view recovering. The secondary purpose was to explore the role of technology to support stroke survivors in remote locations along their recovery journey. METHODS: A qualitative study was undertaken using elements of constructivist grounded theory for data collection and analysis. Semi-structured interviews were conducted with fifteen stroke survivors and two partners living, working or travelling in remote NWQ. RESULTS: From the participants' perspective, recovering in a remote area after stroke is about living my life, as it evolves by endeavouring to recover my way and navigating my recovery in my world. Technology was only considered helpful when it supported participants to recover their way in their world. CONCLUSION: Recovering from stroke from the perspective of stroke survivors in remote NWQ is about living their life, as they want it to be, and as it unfolds within their own context. Technology only has a place when it can support them to recover their way in their world. These findings reinforce the importance of health professionals listening, learning about, and enabling stroke survivors along their recovery journey, within their remote context and support network.Implications for RehabilitationRecovering from the perspective of stroke survivors is about living their life as it evolves.To support stroke survivors from remote areas, health professionals need to listen to and learn from each stroke survivor about what matters to them, what works for them, and about their world; including the challenges (e.g., switching between services) and enablers (e.g., community support) as the stroke survivor perceives them.Finding ways to utilise the strengths within and around them, may improve the recovery process for the stroke survivor in a remote area, ensuring they can access care that meets their needs in their world.Working together with stroke survivors, health professionals need to consider how technology could help them to live their life, while recovering their way and in their world.
Subject(s)
Stroke Rehabilitation , Stroke , Humans , Qualitative Research , Queensland , SurvivorsABSTRACT
Constipation is a common but not a universal feature in early PD, suggesting that gut involvement is heterogeneous and may be part of a distinct PD subtype with prognostic implications. We analysed data from the Parkinson's Incidence Cohorts Collaboration, composed of incident community-based cohorts of PD patients assessed longitudinally over 8 years. Constipation was assessed with the MDS-UPDRS constipation item or a comparable categorical scale. Primary PD outcomes of interest were dementia, postural instability and death. PD patients were stratified according to constipation severity at diagnosis: none (n = 313, 67.3%), minor (n = 97, 20.9%) and major (n = 55, 11.8%). Clinical progression to all three outcomes was more rapid in those with more severe constipation at baseline (Kaplan-Meier survival analysis). Cox regression analysis, adjusting for relevant confounders, confirmed a significant relationship between constipation severity and progression to dementia, but not postural instability or death. Early constipation may predict an accelerated progression of neurodegenerative pathology.
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Common variable immunodeficiency disorders (CVID) are multi-system disorders where target organ damage is mediated by infective, autoimmune and inflammatory processes. Bronchiectasis is probably the most common disabling complication of CVID. The risk factors for bronchiectasis in CVID patients are incompletely understood. The New Zealand CVID study (NZCS) is a nationwide longitudinal observational study of adults, which commenced in 2006. In this analysis, the prevalence and risk factors for bronchiectasis were examined in the NZCS. After informed consent, clinical and demographic data were obtained with an interviewer-assisted questionnaire. Linked electronic clinical records and laboratory results were also reviewed. Statistical methods were applied to determine if variables such as early-onset disease, delay in diagnosis and increased numbers of infections were associated with greater risk of bronchiectasis. One hundred and seven adult patients with a diagnosis of CVID are currently enrolled in the NZCS, comprising approximately 70% of patients known to have CVID in New Zealand. Fifty patients (46·7%) had radiologically proven bronchiectasis. This study has shown that patients with compared to those without bronchiectasis have an increased mortality at a younger age. CVID patients with bronchiectasis had a greater number of severe infections consequent to early-onset disease and delayed diagnosis. Indigenous Maori have a high prevalence of CVID and a much greater burden of bronchiectasis compared to New Zealand Europeans. Diagnostic latency has not improved during the study period. Exposure to large numbers of infections because of early-onset disease and delayed diagnosis was associated with an increased risk of bronchiectasis. Earlier diagnosis and treatment of CVID may reduce the risk of bronchiectasis and premature death in some patients.
Subject(s)
Bronchiectasis/immunology , Common Variable Immunodeficiency/immunology , Cohort Studies , Delayed Diagnosis , Female , Humans , Immunoglobulins, Intravenous/immunology , Longitudinal Studies , Male , Middle Aged , New Zealand , PrevalenceABSTRACT
INTRODUCTION: Mounting evidence supports the existence of an important feedforward cycle between sleep and neurodegeneration, wherein neurodegenerative diseases cause sleep and circadian abnormalities, which in turn exacerbate and accelerate neurodegeneration. If so, sleep therapies bear important potential to slow progression in these diseases. FINDINGS: This cycle is challenging to study, as its bidirectional nature renders cause difficult to disentangle from effect. Likewise, well-controlled intervention studies are often impractical in the setting of established neurodegenerative disease. It is this that makes understanding sleep and circadian abnormalities in Huntington's disease (HD) important: as a monogenic fully penetrant neurodegenerative condition presenting in midlife, it provides a rare opportunity to study sleep and circadian abnormalities longitudinally, prior to and throughout disease manifestation, and in the absence of confounds rendered by age and comorbidities. It also provides potential to trial sleep therapies at a preclinical or early disease stage. Moreover, its monogenic nature facilitates the development of transgenic animal models through which to run parallel pre-clinical studies. HD, therefore, provides a key model condition through which to gain new insights into the sleep-neurodegeneration interface. CONCLUSIONS: Here, we begin by summarising contemporary knowledge of sleep abnormalities in HD, and consider how well these parallel those of Alzheimer's and Parkinson's as more common neurodegenerative conditions. We then discuss what is currently known of the sleep-neurodegeneration cyclical relationship in HD. We conclude by outlining key directions of current and future investigation by which to advance the sleep-neurodegeneration field via studies in HD.
Subject(s)
Huntington Disease , Neurodegenerative Diseases , Animals , Circadian Rhythm , Disease Models, Animal , Huntington Disease/complications , Huntington Disease/genetics , SleepABSTRACT
Purpose Many children begin school with limited vocabularies, placing them at a high risk of academic difficulties. The goal of this study was to examine the effects of a vocabulary intervention program, Story Friends, designed to improve vocabulary knowledge of at-risk preschool children. Method Twenty-four early-childhood classrooms were enrolled in a cluster-randomized design to evaluate the effects of a revised Story Friends curriculum. In each classroom, three to four preschoolers were identified as having poor language abilities, for a total of 84 participants. In treatment classrooms, explicit vocabulary instruction was embedded in prerecorded storybooks and opportunities for review and practice of target vocabulary were integrated into classroom and home practice activities. In comparison classrooms, prerecorded storybooks included target vocabulary, but without explicit instruction, and classroom and home strategies focused on general language enrichment strategies without specifying vocabulary targets to teach. Intervention activities took place over 13 weeks, and 36 challenging, academically relevant vocabulary words were targeted. Results Children in the treatment classrooms learned significantly more words than children in the comparison classrooms, who learned few target words based on exposure. Large effect sizes (mean d = 1.83) were evident as the treatment group averaged 42% vocabulary knowledge versus 11% in the comparison group, despite a gradual decline in vocabulary learning by the treatment group over the school year. Conclusions Findings indicate that a carefully designed vocabulary intervention can produce substantial gains in children's vocabulary knowledge. The Story Friends program is feasible for delivery in early childhood classrooms and effective in teaching challenging vocabulary to high-risk preschoolers. Supplemental Material https://doi.org/10.23641/asha.13158185.
Subject(s)
Child Language , Vocabulary , Child , Child, Preschool , Humans , Language , Language Tests , LearningABSTRACT
OBJECTIVE: Current research does not provide a clear explanation for why some patients with Parkinson's Disease (PD) develop psychotic symptoms. The 'aberrant salience hypothesis' of psychosis has been influential and proposes that dopaminergic dysregulation leads to inappropriate attribution of salience to irrelevant/non-informative stimuli, facilitating the formation of hallucinations and delusions. The aim of this study is to investigate whether non-motivational salience is altered in PD patients and possibly linked to the development of psychotic symptoms. METHODS: We investigated salience processing in 14 PD patients with psychotic symptoms, 23 PD patients without psychotic symptoms and 19 healthy controls. All patients were on dopaminergic medication for their PD. We examined emotional salience using a visual oddball fMRI paradigm that has been used to investigate early stages of schizophrenia spectrum psychosis, controlling for resting cerebral blood flow as assessed with arterial spin labelling fMRI. RESULTS: We found significant differences between patient groups in brain responses to emotional salience. PD patients with psychotic symptoms had enhanced brain responses in the striatum, dopaminergic midbrain, hippocampus and amygdala compared to patients without psychotic symptoms. PD patients with psychotic symptoms showed significant correlations between the levels of dopaminergic drugs they were taking and BOLD signalling, as well as psychotic symptom scores. CONCLUSION: Our study suggests that enhanced signalling in the striatum, dopaminergic midbrain, the hippocampus and amygdala is associated with the development of psychotic symptoms in PD, in line with that proposed in the 'aberrant salience hypothesis' of psychosis in schizophrenia.
Subject(s)
Brain/diagnostic imaging , Emotions/physiology , Parkinson Disease/diagnostic imaging , Psychotic Disorders/diagnostic imaging , Adult , Aged , Amygdala/physiopathology , Brain/physiopathology , Diagnosis, Differential , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Parkinson Disease/complications , Parkinson Disease/physiopathology , Psychotic Disorders/complications , Psychotic Disorders/physiopathology , Schizophrenia/diagnostic imaging , Schizophrenia/physiopathologyABSTRACT
PURPOSE: Human pluripotent stem cell (hPSC)-derived dopaminergic neuron progenitor cells (DAPCs) are a potential therapy for Parkinson's disease (PD). However, their intracranial administration raises safety concerns including uncontrolled proliferation, migration and inflammation. Here, we apply a bimodal imaging approach to investigate the fate of DAPC transplants in the rat striatum. PROCEDURES: DAPCs co-expressing luciferase and ZsGreen or labelled with micron-sized particles of iron oxide (MPIOs) were transplanted in the striatum of RNU rats (n = 6 per group). DAPCs were tracked in vivo using bioluminescence and magnetic resonance (MR) imaging modalities. RESULTS: Transgene silencing in differentiating DAPCs accompanied with signal attenuation due to animal growth rendered the bioluminescence undetectable by week 2 post intrastriatal transplantation. However, MR imaging of MPIO-labelled DAPCs showed that transplanted cells remained at the site of injection for over 120 days. Post-mortem histological analysis of DAPC transplants demonstrated that labelling with either luciferase/ZsGreen or MPIOs did not affect the ability of cells to differentiate into mature dopaminergic neurons. Importantly, labelled cells did not elicit increased glial reactivity compared to non-labelled cells. CONCLUSIONS: In summary, our findings support the transplantation of hPSC-derived DAPCs as a safe treatment for PD.
Subject(s)
Dopaminergic Neurons/cytology , Human Embryonic Stem Cells/cytology , Luminescent Measurements , Magnetic Resonance Imaging , Neural Stem Cells/transplantation , Stem Cell Transplantation , Animals , Brain/diagnostic imaging , Carcinogenesis/pathology , Cell Differentiation , Cell Line , Ferric Compounds/chemistry , Genes, Reporter , Glial Fibrillary Acidic Protein/metabolism , Humans , Male , Neural Stem Cells/cytology , Neuroglia/metabolism , Particle Size , RatsABSTRACT
Learning to read and spell is an important but difficult achievement for children who have complex communication needs. Given that assessment is a vital part of any intervention program, one major barrier is the lack of reliable and valid assessments for this population. This study evaluated the reliability and validity of Dynamic Assessment of the Alphabetic Principle (DAAP), which does not require spoken responses. For this study, 27 preschool and school-aged children with typical development completed the DAAP and other standard measures of phonemic awareness and early literacy. Results indicated the DAAP had high internal consistency and strong correlations among its subtests, indicating high reliability. Moreover, performance on the DAAP had high correlations with standard measures of phonemic awareness and early literacy, providing evidence of its validity. Consequently, the DAAP represents one approach to fill the important need for assessments of early literacy that do not require speech responses.
Subject(s)
Literacy , Phonetics , Child , Child, Preschool , Communication Aids for Disabled , Communication Disorders/rehabilitation , Female , Healthy Volunteers , Humans , Language Tests , Male , Reading , Reproducibility of ResultsABSTRACT
BACKGROUND: Cross-sectional studies have identified that the prevalence of neuropsychiatric symptoms (NPS) in Parkinson's disease (PD) ranges from 70-89%. However, there are few longitudinal studies determining the impact of NPS on quality of life (QoL) in PD patients and their caregivers. We seek to determine the progression of NPS in early PD. METHODS: Newly diagnosed idiopathic PD cases (n = 212) and age-matched controls (n = 99) were recruited into a longitudinal study. NPS were assessed using the Neuropsychiatric Inventory with Caregiver Distress scale (NPI-D). Further neuropsychological and clinical assessments were completed by participants, with reassessment at 18 and 36 months. Linear mixed-effects modelling determined factors associated with NPI-D and QoL over 36 months. RESULTS: Depression, anxiety, apathy and hallucinations were more frequent in PD than controls at all time points (p < 0.05). Higher motor severity at baseline was associated with worsening NPI-D scores over time (ß = 0.1, p < 0.05), but not cognition. A higher NPI total score was associated with poorer QoL at any time point (ß = 0.3, p < 0.001), but not changed in QoL scores. CONCLUSION: NPS are significantly associated with poorer QoL, even in early PD. Screening for NPS from diagnosis may allow efficient delivery of better support and treatment to patients and their families.
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This ex-post facto study reanalyzed data from Romski et al. to examine whether intervention focus moderated the relationship between pre-intervention standardized measures of receptive language and post-intervention standardized measures of receptive and expressive language age and observations of expressive target vocabulary size. In all, 62 toddlers with developmental delay were randomly assigned to augmented communication-input (AC-I), augmented communication-output (AC-O), or spoken communication (SC) interventions. AC-I provided augmented language input via spoken language and a speech-generating device (SGD); AC-O encouraged the production of augmented output via an SGD; and SC provided spoken input and encouraged spoken output without using an SGD. Intervention focus moderated the impact of initial receptive language on expressive language age and expressive target vocabulary size. Participants in AC-I, when compared to those in the other two interventions, had a significantly stronger relationship between initial receptive language and post-intervention expressive language age. For expressive target vocabulary size, participants in AC-O showed a strong relationship and those in AC-I a slightly weaker relationship between initial receptive language and expressive target vocabulary size; no significant relationship was found in the SC group. Results emphasize that different interventions may have distinct outcomes for children with higher or lower initial receptive language.
Subject(s)
Communication Aids for Disabled , Developmental Disabilities/rehabilitation , Language Development Disorders/rehabilitation , Speech Therapy/methods , Child, Preschool , Female , Humans , Infant , Language Tests , Male , Prognosis , VocabularyABSTRACT
Objective: to investigate the impact of the availability and supply of social care on healthcare utilisation (HCU) by older adults in high income countries. Design: systematic review and meta-analysis. Data sources: medline, EMBASE, Scopus, Health Management Information Consortium, Cochrane Database of Systematic Reviews, NIHR Health Technology Assessment, NHS Economic Evaluation Database, Database of Abstracts of Reviews of Effectiveness, SCIE Online and ASSIA. Searches were carried out October 2016 (updated April 2017 and May 2018). (PROSPERO CRD42016050772). Study selection: observational studies from high income countries, published after 2000 examining the relationship between the availability of social care (support at home or in care homes with or without nursing) and healthcare utilisation by adults >60 years. Studies were quality assessed. Results: twelve studies were included from 11,757 citations; ten were eligible for meta-analysis. Most studies (7/12) were from the UK. All reported analysis of administrative data. Seven studies were rated good in quality, one fair and four poor. Higher social care expenditure and greater availability of nursing and residential care were associated with fewer hospital readmissions, fewer delayed discharges, reduced length of stay and expenditure on secondary healthcare services. The overall direction of evidence was consistent, but effect sizes could not be confidently quantified. Little evidence examined the influence of home-based social care, and no data was found on primary care use. Conclusions: adequate availability of social care has the potential to reduce demand on secondary health services. At a time of financial stringencies, this is an important message for policy-makers.
Subject(s)
Health Services for the Aged/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Social Work/statistics & numerical data , Aged , HumansABSTRACT
BACKGROUND: A wealth of evidence implicates both central and peripheral immune changes as contributing to the pathogenesis of Parkinson's disease (PD). It is critical to better understand this aspect of PD given that it is a tractable target for disease-modifying therapy. Age-related changes are known to occur in the immune system (immunosenescence) and might be of particular relevance in PD given that its prevalence rises with increasing age. We therefore sought to investigate this with respect to T cell replicative senescence, a key immune component of human ageing. METHODS: Peripheral blood mononuclear cells were extracted from blood samples from 41 patients with mild PD (Hoehn and Yahr stages 1-2, mean (SD) disease duration 4.3 (1.2) years) and 41 age- and gender-matched controls. Immunophenotyping was performed with flow cytometry using markers of T lymphocyte activation and senescence (CD3, CD4, CD8, HLA-DR, CD38, CD28, CCR7, CD45RA, CD57, CD31). Cytomegalovirus (CMV) serology was measured given its proposed relevance in driving T cell senescence. RESULTS: Markers of replicative senescence in the CD8+ population were strikingly reduced in PD cases versus controls (reduced CD57 expression (p = 0.005), reduced percentage of 'late differentiated' CD57loCD28hi cells (p = 0.007) and 'TEMRA' cells (p = 0.042)), whilst expression of activation markers (CD28) was increased (p = 0.005). This was not driven by differences in CMV seropositivity. No significant changes were observed in the CD4 population. CONCLUSIONS: This study demonstrates for the first time that the peripheral immune profile in PD is distinctly atypical for an older population, with a lack of the CD8+ T cell replicative senescence which characterises normal ageing. This suggests that 'abnormal' immune ageing may contribute to the development of PD, and markers of T cell senescence warrant further investigation as potential biomarkers in this condition.
Subject(s)
Aging/pathology , Immunosenescence , Parkinson Disease/pathology , T-Lymphocytes/metabolism , Aged , Antigens, CD/metabolism , Case-Control Studies , Cellular Senescence , Cytomegalovirus/immunology , Female , Flow Cytometry , Humans , Immunoglobulin G , Immunophenotyping , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Parkinson Disease/blood , SerologyABSTRACT
BACKGROUND: Psoriasis is a chronic T-cell-mediated skin disease with marked social and economic burdens. Current treatments are unsatisfactory, with unpredictable remission times and incompletely understood modes of action. Recent advances in our understanding of the pathogenesis of psoriasis have identified the imbalance between CD4+ T effector cells, particularly the T helper (Th)17 subset, and regulatory T cells (Tregs) as key to the development of psoriatic lesions, and therefore a novel therapeutic target. OBJECTIVES: To quantify in patients the effects of three commonly used psoriasis treatment modalities on the Th1, Th2, Th17 and Treg subsets, and to test whether any change correlates with clinical response. METHODS: Flow cytometry was used to enumerate Th1, Th2, Th17 and Treg subsets in blood and skin of patients with psoriasis before and after receiving any of the following treatments: narrowband ultraviolet B (NB-UVB), adalimumab and topical betamethasone-calcipotriol combination (Dovobet® ) RESULTS: All patients responded clinically to the treatments. NB-UVB significantly increased the numbers of circulating and skin Tregs, while, by contrast, adalimumab reduced Th17 cells in these compartments, and Dovobet had dual effects by both increasing Tregs and reducing Th17 cells. CONCLUSIONS: The differential effects reported here for the above-mentioned treatment modalities could be exploited to optimize or design therapeutic strategies to overcome the inflammatory drivers more effectively and restore the Th17-Treg balance in psoriasis.
Subject(s)
Adalimumab/therapeutic use , Betamethasone/analogs & derivatives , Calcitriol/analogs & derivatives , Dermatologic Agents/therapeutic use , Psoriasis/drug therapy , T-Lymphocytes, Regulatory/drug effects , Ultraviolet Therapy , Administration, Cutaneous , Betamethasone/therapeutic use , Calcitriol/therapeutic use , Drug Combinations , Female , Humans , Lymphocytosis/chemically induced , Lymphopenia/chemically induced , Male , Middle Aged , Ointments , T-Lymphocyte Subsets , T-Lymphocytes, Regulatory/radiation effects , Th17 Cells/drug effects , Th17 Cells/radiation effectsABSTRACT
WHAT IS KNOWN ON THE SUBJECT: Person-centered care, as compared to standard approaches, is a widely accepted, evidence-based approach for managing aggressive behaviour in persons with dementia. The attitudes, beliefs and values of long-term care and mental health nursing employees are important prerequisites to implementing person-centered practices. Research shows that nursing employees typically support person-centered approaches; however, less is known about the attitudes of non-nursing employee groups. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE: Nurse managers and administrators tended to agree with person-centered approaches for managing aggression in dementia, suggesting some prerequisites are in place to support wider adoption of person-centered frameworks. Employees with more resident contact tended to support person-centered approaches the least, suggesting discipline-specific trainings may not be adequate for preparing frontline staff to use person-centered techniques. Attitudes towards aggressive behaviour may be especially varied and contradictory within certain employee groups, providing implications for facility-wide initiatives. IMPLICATIONS FOR PRACTICE: Person-centered values and practices should be monitored and reinforced across the organization. Person-centered trainings should be interdisciplinary in nature and focused on care areas, such as mealtime or bathing. Long-term care facilities should consider allowing nurse management and registered nurses to share the burden of direct resident care with frontline employees on a more regular basis. ABSTRACT: Introduction Implementing person-centered care requires shared attitudes, beliefs and values among all care employees. Existing research has failed to examine the attitudes of non-nursing employees. Aim This study examined attitudes towards aggression among nursing and non-nursing employees to address gaps in existing research and assess readiness for wider adoption of person-centered frameworks. Method The Management of Aggression in People with Dementia Attitude Questionnaire was used to survey attitudes of employees in Michigan-based nursing homes. Results Overall, employees preferred person-centered over standard approaches. Job title was a significant predictor of paradigm support. Frontline employees were found to support person-centered attitudes the least. Wide-ranging responses were noted within employee groups. Discussion Job title may influence the degree to which an employee supports and utilizes person-centered approaches. Employees with the most contact with persons with dementia may be the least likely to implement person-centered approaches. In contrast to prior studies, years of experience was not a significant predictor of attitude towards aggressive behaviour. Wide-ranging responses indicate that employee attitudes are varied and complex. Implications Person-centered approaches should be trained within care areas rather than individual employee groups. Programs should be interdisciplinary and seek to establish a shared understanding of person-centered beliefs and values.
Subject(s)
Aggression , Attitude of Health Personnel , Dementia/nursing , Long-Term Care , Patient-Centered Care , Adult , Dementia/complications , HumansABSTRACT
OBJECTIVE: To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline. METHODS: FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8â months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18â months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA. RESULTS: PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (ß=0.38, p=0.001) and MoCA (ß=0.3, p=0.002) at 18â months controlling for baseline score. CONCLUSIONS: Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia.
Subject(s)
Blood Glucose/metabolism , Brain/diagnostic imaging , Fluorodeoxyglucose F18 , Parkinson Disease/blood , Parkinson Disease/diagnostic imaging , Positron-Emission Tomography , Aged , Aged, 80 and over , Brain Mapping , Cognitive Dysfunction/blood , Cognitive Dysfunction/diagnostic imaging , Cohort Studies , England , Female , Humans , Longitudinal Studies , Male , Mental Status Schedule , Middle Aged , Statistics as TopicABSTRACT
Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by a triad of motor, psychiatric and cognitive deficits with the latter classically attributed to disruption of fronto-striatal circuits. However, emerging evidence suggests that some of the cognitive deficits in HD may have their origin in other structures including the hippocampus. Hippocampal abnormalities have been reported in HD mouse models particularly in terms of performance on the Morris Water Maze. However, in these animals, it is difficult to be certain whether the spatial memory deficits are due to local pathology within this structure or their poor mobility and motivation. Thus, a better model of hippocampal dysfunction in HD is needed especially given that we have previously shown that patients with HD have hippocampal-related problems from the very earliest stages of disease. In this study, our aim was therefore to understand the cellular and behavioural consequences of local overexpression of mutant huntingtin (mHTT) in the hippocampus of adult mice. We found that a targeted injection of a lentivirus, encoding an N-terminal of mHTT with 82 CAG repeats, into the murine hippocampus led to the focal formation of mHTT aggregates, long-term spatial memory impairments with decreased neurogenesis and expression of the immediate early gene c-fos. This study has therefore shown for the first time that local expression of mHTT in the dentate gyrus has deleterious effects, including its neurogenic capacity, with functional behavioural consequences, which fits well with recent data on hippocampal deficits seen in patients with HD.