Objective To investigate intrathecal inflammation using cerebrospinal fluid (CSF) cytokines and chemokines in a subgroup of pediatric epilepsy patients with frequent daily seizures. Methods We measured 32 cytokines/chemokines using multiplex immunoassay in CSF collected from pediatric patients with febrile infection‐related epilepsy syndrome (FIRES)/FIRES‐related disorders (FRD; n = 6), febrile status epilepticus (FSE; n = 8), afebrile status epilepticus (ASE; n = 8), and chronic epilepsy with frequent daily seizures (n = 21) and compared the results with noninflammatory neurological disorders (NIND; n = 20) and encephalitis (n = 43). We also performed longitudinal CSF cytokine/chemokine studies in three cases with FIRES/FRD. Results The median age of onset of seizures was 2.4 years (range = 0.08‐12.5). Median CSF timing from the onset of seizures was longer in chronic epilepsy (540 days), whereas FIRES, FSE, and ASE had CSF tested within 1‐2 days of onset of seizures (P < .001). The elevation of cytokines/chemokines was higher in FIRES followed by FSE, when compared to chronic epilepsy and NIND controls. Th1‐associated cytokines/chemokines (TNF‐α, CXCL9, CXCL10, CXCL11), IL‐6, CCL2, CCL19, and CXCL1 (P < .05) were elevated in FIRES, in contrast to the elevation of a broader network of cytokines/chemokines in encephalitis. The cytokines/chemokines (CXCL9, CXCL10, CXCL11, and CCL19) were elevated in FSE when compared to ASE despite the similar median seizure duration and timing of CSF testing in relation to seizures. Chronic epilepsy generally lacked significant elevation of cytokines/chemokines despite frequent daily seizures. The median concentrations of the cytokines/chemokines rapidly declined on serial testing during the course of illness in all three FIRES/FRD cases. Significance We identify significant differences in CSF cytokine/chemokine profile between FIRES/FRD and encephalitis. The prominent elevation of CSF cytokines and chemokines in FIRES/FRD and to a lesser extent FSE highlights that the cytokine/chemokine elevation is significantly associated with the etiology of the underlying process rather than purely reactive. However, it is unclear whether the immune activation contributes to the disease process.
Expressions for the bias of the least-squares and modified Yule-Walker estimators in a correctly specified multivariate autoregression of arbitrary order are obtained without assuming that the innovations are Gaussian. Instead, the innovations are assumed to form a martingale difference sequence which is stationary up to sixth order and which has finite sixth moments. The errors in the expressions are shown to be O(n-3rz), as the sample size n + 03, under some moment conditions. The expressions obtained are the same in the Gaussian and non-Gaussian cases.
12011 Background: Older people experience significant adverse effects of cancer and anti-cancer therapy due to age-related vulnerabilities, including medical, functional, cognitive, nutritional and psychosocial issues. Comprehensive geriatric assessment and management (CGAM) provides a powerful framework to assess an older person’s health status and offers a coordinated, person-centered approach to care. Despite its effectiveness, the uptake of CGAM in oncology has been limited due to a lack of randomized evidence in this setting. This study evaluated the effectiveness of CGAM in older people with cancer. Methods: INTEGERATE is a prospective, randomized, parallel group, open-label study in patients aged >70 years with cancer planned for chemotherapy, targeted therapy or immunotherapy. Patients were randomly assigned (1:1) to receive either geriatrician-led CGAM integrated with usual care (integrated oncogeriatric care) or usual care alone, using minimization to balance treatment intent, cancer type, age, sex and performance status. Health-related quality of life (HRQOL) was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-ELD14 at 0, 12, 18 and 24 weeks. The primary outcome was HRQOL measured by the validated Elderly Functional Index (ELFI) score. Major secondary outcomes included function, mood, nutrition, health utility, treatment delivery, healthcare utilization and survival. Results: Of the 154 patients who underwent randomization, 13 died by week 12 and 130 (92.2% of the remaining patients) completed at least two primary outcome assessments. For the primary outcome, patients in the intervention group had significantly better ELFI score than the usual care group across all followup timepoints, with a maximal difference at week 18 (estimated marginal mean ELFI score 72.0 vs 58.7, p= 0.001). In addition, significant differences favoring the intervention group over the usual care group were seen in HRQOL (domains: physical, role and social functioning; mobility, burden of illness and future worries), unplanned hospital admissions (-1.2 admissions per person-years, p< 0.001) and early treatment discontinuation (32.9% vs 53.2%, p = 0.01). Conclusions: Integrated oncogeriatric care led to improvements in HRQOL, unplanned hospital admissions and treatment discontinuation in older people receiving systemic anti-cancer therapy. Older people (>70 years) planned for anti-cancer therapy should receive CGAM to optimize their clinical care and health outcomes. Clinical trial information: ACTRN12614000399695 .
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