Background and Purpose—: Poststroke pneumonia is a potentially preventable complication after stroke associated with poor outcome. We developed and externally validated a prognostic score for predicting risk of pneumonia after ischemic stroke. Methods—: The prognostic score was developed based on clinical data routinely collected after admission from the Berlin Stroke Register, Germany. The association of demographics, comorbidities, and clinical characteristics with poststroke pneumonia was investigated using multivariable logistic regression analyses. Independent predictors of poststroke pneumonia were translated into a point scoring system based on the corresponding regression coefficients. The predictive properties of the developed prognostic score were externally validated using an independent data set from the Stroke Register Northwest-Germany. Results—: Between 2007 and 2009, 15 335 patients with ischemic stroke were registered within the Berlin Stroke Register. The observed rate of pneumonia in hospital was 7.2%. A 10-point score was derived for prediction of poststroke pneumonia (Age ≥75 years=1, Atrial fibrillation=1, Dysphagia=2, male Sex=1, stroke Severity, National Institutes of Health Stroke Scale 0–4=0, 5–15=3, ≥16=5; A 2 DS 2 ). The proportion of pneumonia varied between 0.3% in patients with a score of 0 point to 39.4% in patients with a score of 10 points. The score demonstrated excellent discrimination (C-statistic 0.84; 95% CI, 0.83–0.85) and calibration (McFadden R2 =0.21). Prediction, discrimination, and calibration properties were reproduced in the validation cohort consisting of 45 085 patients with ischemic stroke. Conclusions—: The A 2 DS 2 score is a valid tool for predicting poststroke pneumonia based on routinely available data. A 2 DS 2 might be useful for guiding monitoring of high-risk patients or prophylactic pneumonia management in clinical routine.
14 October 2016 in Journal of Cerebral Blood Flow & Metabolism
Stroke-associated pneumonia is a frequent complication after stroke associated with poor outcome. Dysphagia is a known risk factor for stroke-associated pneumonia but accumulating evidence suggests that stroke induces an immunodepressive state increasing susceptibility for stroke-associated pneumonia. We aimed to confirm that stroke-induced immunodepression syndrome is associated with stroke-associated pneumonia independently from dysphagia by investigating the predictive properties of monocytic HLA-DR expression as a marker of immunodepression as well as biomarkers for inflammation (interleukin-6) and infection (lipopolysaccharide-binding protein). This was a prospective, multicenter study with 11 study sites in Germany and Spain, including 486 patients with acute ischemic stroke. Daily screening for stroke-associated pneumonia, dysphagia and biomarkers was performed. Frequency of stroke-associated pneumonia was 5.2%. Dysphagia and decreased monocytic HLA-DR were independent predictors for stroke-associated pneumonia in multivariable regression analysis. Proportion of pneumonia ranged between 0.9% in the higher monocytic HLA-DR quartile (≥21,876 mAb/cell) and 8.5% in the lower quartile (≤12,369 mAb/cell). In the presence of dysphagia, proportion of pneumonia increased to 5.9% and 18.8%, respectively. Patients without dysphagia and normal monocytic HLA-DR expression had no stroke-associated pneumonia risk. We demonstrate that dysphagia and stroke-induced immunodepression syndrome are independent risk factors for stroke-associated pneumonia. Screening for immunodepression and dysphagia might be useful for identifying patients at high risk for stroke-associated pneumonia.
Objectives: Emerging evidence suggests that fatigue in myasthenia gravis (MG) is a relevant problem that negatively impacts activities of daily living (ADL). The relationship between fatigue and quality of life (QoL) has never been systematically explored in MG patients. The study aimed to assess the prevalence of fatigue and its relation to ADL and QoL as well as to identify factors associated with fatigue in MG.Material and Methods: This was a cross‐sectional observational study in patients with confirmed diagnosis of MG independent of disease severity. Prevalence of fatigue was assessed using the Chalder Fatigue Scale (CFQ). Impact of fatigue on ADL and QoL was assessed by the MG activities of daily living profile (MG‐ADL) and the MG‐specific quality‐of‐life instrument (MG‐QoL), respectively. Association of fatigue with sociodemographics, clinical characteristics of MG, and comorbidities including mood and anxiety disorders as well as sleep disorders was investigated using multivariable logistic regression analyses.Results: Overall, 200 MG patients were included. The observed rate of fatigue was 56.1%, of those 70.4% fulfilled the criteria of chronic fatigue (CF) with a duration of ≥6 months. Relevant fatigue was strongly associated to ADL and QoL. Factors associated with relevant fatigue were disease severity and depressive state. Furthermore, positive muscle‐specific tyrosine kinase (MuSK) antibody status showed a strong association with relevant fatigue.Conclusions: MG patients have a high prevalence of fatigue which negatively impacts ADL and QoL. MG‐specific clinical characteristics are related to fatigue and might help to identify MG patients at risk for fatigue.
Myasthenia gravis (MG) is a rare autoimmune disease characterised by exertion-induced muscle weakness that can lead to potentially life-threatening myasthenic crises. Detectable antibodies are directed against specific postsynaptic structures of the neuromuscular junction. MG is a chronic condition that can be improved through therapies, but to date, not cured. Standard treatment has been unchanged for decades and includes symptomatic treatment with acetylcholine-esterase inhibitors and disease-modifying treatment with steroids, steroid-sparing immunosuppressants and thymectomy. Overall, a relevant proportion of patients does not achieve a satisfactory clinical improvement under standard treatment. Additionally, long-term therapy with steroids can cause significant side effects and latency to clinical improvement with standard steroid-sparing immunosuppressants and after thymectomy can take months to years. In recent years, treatment of MG has changed fundamentally due to improved evidence from phase 3 trials and the regulatory approval of complement inhibitors and FcRn inhibitors as add-on treatment options. This provides new optimism for substantially more patients reaching minimal manifestation status and has led to a shift in treatment strategy with more targeted therapies being employed early in the course of the disease, especially in patients with high disease activity. In this focussed review, we provide an overview of the diagnosis, classification and standard treatment of MG, followed by data from randomised controlled trials on the modern drugs already available for therapy and those still in the final stages of clinical development. In the second part, we provide an overview of real-world data for already approved therapies and outline how the availability of new biologicals is changing both clinical decision-making and patient journey.
Glucocorticoids (GC) are the most commonly used immune‐directed therapy in myasthenia gravis (MG). However, to date, GC have not proven their effectiveness in the setting of a randomized clinical trial that complies with currently accepted standards. The rationale for the use of GC in MG is the autoimmune nature of the disease, which is supported by consistent positive results from retrospective studies. Well‐defined recommendations for treatment of MG with GC are lacking and further hampered by inter‐ and intra‐individual differences in the disease course and responses to GC treatment. Uncertainties concerning GC treatment in MG encompass the indication for treatment initiation, exact dosage, dose adjustment in specific conditions (e.g., pregnancy, thymectomy), mode of tapering, and surveillance of adverse events (AE). This review illustrates the mode of action of GC in the treatment for MG, presents the currently available data on GC treatment in MG, and attempts to translate the currently available information into clinical recommendations.