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BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease that damages myelin in the central nervous system (CNS). We investigated the profile of CCN3, a known regulator of immune function and a potential mediator of myelin regeneration, in multiple sclerosis in the context of disease state and disease-modifying treatment. METHODS: CCN3 expression was analysed in plasma, immune cells, CSF and brain tissue of MS patient groups and control subjects by ELISA, western blot, qPCR, histology and in situ hybridization. RESULTS: Plasma CCN3 levels were comparable between collective MS cohorts and controls but were significantly higher in progressive versus relapsing-remitting MS and between patients on interferon-ß versus natalizumab. Higher body mass index was associated with higher CCN3 levels in controls as reported previously, but this correlation was absent in MS patients. A significant positive correlation was found between CCN3 levels in matched plasma and CSF of MS patients which was absent in a comparator group of idiopathic intracranial hypertension patients. PBMCs and CD4+ T cells significantly upregulated CCN3 mRNA in MS patients versus controls. In the CNS, CCN3 was detected in neurons, astrocytes and blood vessels. Although overall levels of area immunoreactivity were comparable between non-affected, demyelinated and remyelinated tissue, the profile of expression varied dramatically. CONCLUSIONS: This investigation provides the first comprehensive profile of CCN3 expression in MS and provides rationale to determine if CCN3 contributes to neuroimmunological functions in the CNS.
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Interferón beta/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/metabolismo , Natalizumab/uso terapéutico , Proteína Hiperexpresada del Nefroblastoma/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteína Hiperexpresada del Nefroblastoma/genética , Resultado del TratamientoRESUMEN
PURPOSE: While pain is prevalent among survivors of head and neck cancer (HNC), there is a lack of data on pain management in the community oncology setting. We described sociodemographic correlates and disparities associated with patient-reported pain among patients with HNC. METHODS: We used the 2017-2021 nationwide community oncology data set from Navigating Cancer, which included electronic patient-reported outcomes. We identified a retrospective cohort of patients diagnosed with HNC (N = 25,572), with ≥ 1 patient-reported pain event. We adjusted for demographic (sex, age, smoking history, marital status) and clinical (cancer site) factors associated with pain reporting and pain resolution by new pain prescription on the basis of race (White v non-White patients), using multivariate logistic regression models. RESULTS: Our analytic cohort included 2,331 patients, 90.58% White, 58.62% married, with an average age of 66.47 years. Of these, 857 patients (36.76%) reported ≥ 1 pain event during study period. Mean resolution time (in minutes) for pain incidents was significantly longer for White patients than non-White patients (99.6 ± 3.2 v 74.9 ± 7.2, P < .05). After adjusting for covariates, smoking was associated with a 25% increased odds of reporting pain incidents (adjusted odds ratio [aOR], 1.25; 95% CI, 1.03 to 1.52). There was no statistically significant difference in odds of pain reporting between White versus non-White patients (aOR, 0.97; 95% CI, 0.73 to 1.30). However, White patients were significantly more likely to receive new prescription for pain than non-White patients (aOR, 2.52; 95% CI, 1.09 to 5.86). CONCLUSION: We found racial differences in patient-reported pain management, with White patients significantly more likely to receive new pain prescriptions. As pain management is a mainstay in cancer care, equity in pain management is critical to optimize quality of life for patients with HNC.
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Neoplasias de Cabeza y Cuello , Manejo del Dolor , Humanos , Anciano , Estudios Retrospectivos , Calidad de Vida , Dolor , Medición de Resultados Informados por el PacienteRESUMEN
The extent of grey matter demyelination and neurodegeneration in the progressive multiple sclerosis (PMS) brains at post-mortem associates with more severe disease. Regional tissue atrophy, especially affecting the cortical and deep grey matter, including the thalamus, is prognostic for poor outcomes. Microglial and complement activation are important in the pathogenesis and contribute to damaging processes that underlie tissue atrophy in PMS. We investigated the extent of pathology and innate immune activation in the thalamus in comparison to cortical grey and white matter in blocks from 21 cases of PMS and 10 matched controls. Using a digital pathology workflow, we show that the thalamus is invariably affected by demyelination and had a far higher proportion of active inflammatory lesions than forebrain cortical tissue blocks from the same cases. Lesions were larger and more frequent in the medial nuclei near the ventricular margin, whilst neuronal loss was greatest in the lateral thalamic nuclei. The extent of thalamic neuron loss was not associated with thalamic demyelination but correlated with the burden of white matter pathology in other forebrain areas (Spearman r = 0.79, p < 0.0001). Only thalamic neuronal loss, and not that seen in other forebrain cortical areas, correlated with disease duration (Spearman r = -0.58, p = 0.009) and age of death (Spearman r = -0.47, p = 0.045). Immunoreactivity for the complement pattern recognition molecule C1q, and products of complement activation (C4d, Bb and C3b) were elevated in thalamic lesions with an active inflammatory pathology. Complement regulatory protein, C1 inhibitor, was unchanged in expression. We conclude that active inflammatory demyelination, neuronal loss and local complement synthesis and activation in the thalamus, are important to the pathological and clinical disease outcomes of PMS.
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Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple , Atrofia/patología , Activación de Complemento , Sustancia Gris/patología , Humanos , Esclerosis Múltiple/patología , Esclerosis Múltiple Crónica Progresiva/patología , Tálamo/patologíaRESUMEN
PURPOSE: Among patients receiving chemotherapy, symptom monitoring with electronic patient-reported outcomes (ePROs) is associated with improved clinical outcomes, satisfaction, and compliance with therapy. Standard approaches for ePRO implementation are not established, warranting evaluation in community cancer practices. We present implementation findings of ePRO symptom monitoring across a large multisite community oncology practice network. METHODS: Patients initiating a new systemic therapy at one of the 210 practice sites at Texas Oncology were invited to use the Navigating Cancer ePRO platform, with stepped-wedge implementation from July to December 2020. Participating patients received a weekly prompt by text message or e-mail to self-report common symptoms and well-being. Severe self-reported symptoms triggered a real-time notification to nursing triage to address the symptom. Enrollment and compliance were systematically tracked weekly with evaluation of barriers and facilitators to adoption and sustainability. RESULTS: Four thousand three hundred seventy-five patients planning systemic treatment were enrolled and participated. Seventy-three percent (1,841 of 2,522) of enrolled patients completed at least one ePRO assessment. Among these individuals, 64% (16,299 of 25,061) of available weekly ePRO assessments were completed. Over a 10-week period, compliance declined from 72% to 52%. Barriers currently being addressed include lack of a second reminder text or e-mail prompt, inconsistent discussion of reported ePROs by clinicians at visits, and COVID-related changes in workflow. Facilitators included ease of use and patient and staff engagement on the importance of PROs for symptom management. CONCLUSION: ePROs can be effectively implemented in community oncology practice. Utilization of ePROs is high but diminishes over time without attention to barriers. Ongoing work to address barriers and optimize compliance are underway.
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COVID-19 , Medición de Resultados Informados por el Paciente , Electrónica , Humanos , Pandemias , SARS-CoV-2 , Encuestas y Cuestionarios , Texas/epidemiologíaRESUMEN
The primary objective of this study was to test the relevance of hydrological classification and class differences to the characteristics of woody riparian vegetation in a subtropical landscape in Queensland, Australia. We followed classification procedures of the environmental flow framework ELOHA - Ecological Limits of Hydrologic Alteration. Riparian surveys at 44 sites distributed across five flow classes recorded 191 woody riparian species and 15, 500 individuals. There were differences among flow classes for riparian species richness, total abundance, and abundance of regenerating native trees and shrubs. There were also significant class differences in the occurrence of three common tree species, and 21 indicator species (mostly native taxa) further distinguished the vegetation characteristics of each flow class. We investigated the influence of key drivers of riparian vegetation structure (climate, depth to water table, stream-specific power, substrate type, degree of hydrologic alteration, and land use) on riparian vegetation. Patterns were explained largely by climate, particularly annual rainfall and temperature. Strong covarying drivers (hydrology and climate) prevented us from isolating the independent influences of these drivers on riparian assemblage structure. The prevalence of species considered typically rheophytic in some flow classes implies a more substantial role for flow in these classes but needs further testing. No relationships were found between land use and riparian vegetation composition and structure. This study demonstrates the relevance of flow classification to the structure of riparian vegetation in a subtropical landscape, and the influence of covarying drivers on riparian patterns. Management of environmental flows to influence riparian vegetation assemblages would likely have most potential in sites dominated by rheophytic species where hydrological influences override other controls. In contrast, where vegetation assemblages are dominated by a diverse array of typical rainforest species, and other factors including broad-scale climatic gradients and topographic variables have greater influence than hydrology, riparian vegetation is likely to be less responsive to environmental flow management.
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OBJECTIVE: to compare the views of general practitioners and hospital staff on the reasons for unplanned readmission of older people. METHODS: we studied 124 patients aged 65 years or over who were readmitted within 28 days of discharge. We determined the views of hospital staff and the patient's general practitioner on the reasons for readmission and compared them using McNemar's test. RESULTS: the crude readmission rate was 13.2%. The commonest agreed reason for readmission was a relapse or complication of the initial illness. Opinions differed most significantly when the reason was poor health or inadequate preparation on discharge. CONCLUSION: hospital discharge policies should take into account general practitioners' views on the causes of unplanned readmission.