Background: Glucocorticoid resistance—reduced function of the glucocorticoid receptor (GR)—is seen in many depressed patients. It is argued that this resistance to glucocorticoids leads to failure of normal feedback regulation on the immune system. High levels of pro-inflammatory cytokines result. Purpose: We sought to identify evidence supporting or refuting a link between glucocorticoid resistance and immune dysregulation in depression and to summarize retrieved evidence in aggregate form. Methods: We systematically reviewed and meta-analyzed studies that examined cytokine levels in depressed patients compared with controls and that also reported a measure of glucocorticoid resistance. These measures included plasma cortisol, the dexamethasone suppression test (DST), GR expression levels, and the results of in vitro assays of GR function. We conducted four separate meta-analyses to test for moderating effects of glucocorticoid resistance on cytokine production in depression. Results: After sub-grouping 32 studies by the ratio of cortisol levels in patients compared with controls, we observed a trend for increasing glucocorticoid resistance (i.e., the most hypercortisolemic patients) to be associated with increased production of interleukin (IL)-6 [ d = 0.94; 95% CI (0.29, 1.59)] and tumour necrosis factor (TNF)-α [ d = 0.46; 95% CI (0.12, 0.79)]. We stratified nine studies that reported DST results by relative glucocorticoid resistance between patients and controls, identifying a trend for higher glucocorticoid resistance in patients, compared with controls, to be associated with higher cytokine production in patients (170 patients and 187 controls). This was particularly evident when studies were sub-grouped by source of cytokine—plasma ( d = 1.04; 95% CI, 0.57–1.50) versus in vitro ( d = 0.24; 95% CI, −0.20 to 0.67). Stratifying the four studies (147 patients and 118 controls) that used in vitro assays of GR function or GR expression to quantify glucocorticoid resistance revealed variable contributions to cytokine production in patients compared with controls (overall effect size: d = 1.35; 95% CI 0.53–2.18). Combining our analyses of studies that reported DST results with those that used in vitro assays of GR function or GR expression to quantify glucocorticoid resistance (302 patients and 277 controls), we noted that although depressed patients produced more cytokines than controls ( d = 1.02; 95% CI, 0.55–1.49), there was no evident positive correlation between glucocorticoid resistance and inflammation. Conclusions: Our work provides some support for a model conceptualizing glucocorticoid resistance...
ObjectiveTo investigate features of Guillain-Barré syndrome (GBS) following SARS-CoV-2 vaccines and evaluate for a causal link between the two.MethodsWe captured cases of GBS after SARS-CoV-2 vaccination through a national, open-access, online surveillance system. For each case, the certainty of GBS was graded using the Brighton criteria, and the relationship to the vaccine was examined using modified WHO Causality Assessment criteria. We compared age distribution of cases with that of prepandemic GBS cases and clinical features with the International GBS Outcome Study (IGOS).ResultsBetween 1 January and 30 June 2021, we received 67 reports of GBS following the ChAdOx1 vaccine (65 first doses) and three reports following the BNT162b2 vaccine (all first doses). The causal association with the vaccine was classified as probable for 56 (80%, all ChAdOx1), possible for 12 (17%, 10 ChAdOx1) and unlikely for two (3%, 1 ChAdOx1). A greater proportion of cases occurred in the 50–59 age group in comparison with prepandemic GBS. Most common clinical variants were sensorimotor GBS (n=55; 79%) and facial diplegia with paraesthesias (n=10; 14%). 10% (n=7/69) of patients reported an antecedent infection, compared with 77% (n=502/652) of the IGOS cohort (p<0.00001). Facial weakness (63% (n=44/70) vs 36% (n=220/620); p<0.00001) and sensory dysfunction (93% (n=63/68) vs 69% (n=408/588); p=0.00005) were more common but disease severity and outcomes were similar to the IGOS study.InterpretationMost reports of GBS followed the first dose of ChAdOx1 vaccine. While our study cannot confirm or refute causation, this observation, together with the absence of alternative aetiologies, different than expected age distribution and the presence of unusual clinical features support a causal link. Clinicians and surveillance bodies should remain vigilant to the possibility of this very rare adverse event and its atypical variants.
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Objective: Functional Neurological Symptoms (FNS) are disabling symptoms without macro-structural cause. While inpatient treatment confers important benefits, it is resource intensive and hence it is important to optimize its efficiency. Methods: We developed a brief, internet-based preparatory therapy based on psychoeducation and CBT, termed the Queen Square Guided Self-help (QGSH) to maximize the efficacy of the inpatient FNS treatment at the National Hospital for Neurology and Neurosurgery. Results: The QGSH aims to ensure that prior to admission the patient understands 1) The diagnosis of FNS , 2) The five areas CBT model and 3) The use of Goal setting in rehabilitation. It has now run since 2017 and 191 patients have taken part in the inpatient FNS program, with 122 of these have participated in the QGSH. It runs for up to twelve weeks and includes original videos and patient worksheets, as well as signposting to existing published resources. Information is sent weekly by e-mail and content is delivered in the form of eleven modules built around online video sessions.Conclusion: We believe that the set of materials used in QGSH has the potential to benefit patients with FNS and can support clinicians wishing to develop their expertise. It could help with the development of new FNS services, and we are in the process of developing it into a standalone service. We hope that the experience of the Queen Square team can be used to help patients and clinicians to improve the provision of FNS services.
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