Complement Profiles in Patients with Amyotrophic Lateral Sclerosis: A Prospective Observational Cohort Study.

BACKGROUND: The complement system has been suggested to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS), a progressive motor neuron disease. In the present study, we compared levels of selected complement markers to clinical outcome in ALS patients. METHODS: This observational, explorative cohort study included 92 ALS patients, 61 neurological controls (NCs) admitted for suspected aneurysmal subarachnoid haemorrhage, and 96 neurologically healthy controls (NHCs). Peripheral blood and cerebrospinal fluid (CSF) were obtained for the measurement of ficolin-1, -2, and -3; collectin-11, MBL, MASP-3, MAP-1, C4, C3, PTX-3, and complement activation products C4c, C3bc, and sC5b-9. We recorded clinical outcomes of ALS patients for 24 to 48 months after inclusion in order to analyse the effects of the complement markers on survival time. RESULTS: Compared with both control groups, ALS patients exhibited increased collectin-11, C4 and sC5b-9 in plasma, as well as increased ficolin-3 in CSF. Ficolin-2 was significantly decreased in plasma of the ALS patients compared with NHCs, but not with NCs. The concentration of collectin-11, C3 and C3bc correlated negatively with the revised ALS functional rating scale (ALSFRS-R). No association was found between levels of complement markers and survival as estimated by hazard ratios. CONCLUSION: ALS patients exhibit aberrant expression of selected mediators of the lectin complement pathway as well as increased activation of the terminal complement pathway, corroborating the notion that the complement system might be involved in the pathophysiology of ALS.

Prediction of survival in amyotrophic lateral sclerosis: a nationwide, Danish cohort study.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with great heterogeneity. Biological prognostic markers are needed for the patients to plan future supportive treatment, palliative treatment, and end-of-life decisions. In addition, prognostic markers are greatly needed for the randomization in clinical trials. OBJECTIVE: This study aimed to test the ALS Functional Rating Scale-Revised (ALSFRS-R) progression rate (ΔFS) as a prognostic marker of survival in a Danish ALS cohort. METHODS: The ALSFRS-R score at test date in association with duration of symptoms, from the onset of symptoms until test date, (defined as ΔFS') was calculated for 90 Danish patients diagnosed with either probable or definite sporadic ALS. Median survival time was then estimated from the onset of symptoms until primary endpoint (either death or tracheostomy). ΔFS' was subjected to survival analysis using Cox proportional hazards modelling, log-rank test, and Kaplan-Meier survival analysis. RESULTS AND CONCLUSIONS: Both ΔFS' and age was found to be strong predictors of survival of the Danish ALS cohort. Both variables are easily obtained at the time of diagnosis and could be used by clinicians and ALS patients to plan future supportive and palliative treatment. Furthermore, ΔFS', is a simple, prognostic marker that predicts survival in the early phase of disease as well as at later stages of the disease.

Optimizing Residents' Performance of Lumbar Puncture: An RCT Comparing the Effect of Preparatory Interventions on Performance and Self-Confidence.

BACKGROUND: Lumbar puncture is often associated with uncertainty and limited experience on the part of residents; therefore, preparatory interventions can be essential. There is growing interest in the potential benefit of videos over written text. However, little attention has been given to whether the design of the videos impacts on subsequent performance. OBJECTIVE: To investigate the effect of different preparatory interventions on learner performance and self-confidence regarding lumbar puncture (LP). DESIGN: Randomized controlled trial in which participants were randomly assigned to one of three interventions as preparation for performing lumbar puncture: 1) goal- and learner-centered video (GLV) presenting procedure-specific process goals and learner-centered information; 2) traditional video (TV) providing expert-driven content, but no process goals; and 3) written text (WT) with illustrations. PARTICIPANTS AND MAIN MEASURES: Participants were PGY-1 doctors without LP experience. After the preparatory intervention, participants performed an LP in a simulated setting with a standardized patient and an assistant. Two content experts, blinded to participant group allocation, assessed video recordings of the performance using the Lumbar Puncture Assessment Tool (LumPAT) and an overall global rating. Participants rated their self-confidence immediately prior to performing the procedure. The primary outcome was the difference in LumPAT scores among groups. KEY RESULTS: A total of 110 PGY-1 doctors were included. Results demonstrated significant differences in LumPAT mean scores among the three groups: GLV, 42.8; TV, 40.6; WT, 38.1 (p = 0.01). The global rating scores were highest in the GLV group (p = 0.026). Self-confidence scores differed significantly among the three groups (p = 0.003), with the TV group scoring the highest. There were no significant correlations between self-confidence scores and performance scores in any of the groups. CONCLUSION: A video designed with procedure-specific process goals and learner-centered information resulted in better subsequent LP performance than a traditionally designed video or written text. Participants' self-confidence was not predictive of their actual performance.

Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease: effect of l-DOPA treatment and changes in levodopa-induced dyskinesia.

Levodopa (l-DOPA, l-3,4-dihydroxyphenylalanine) is the most effective drug in the symptomatic treatment of Parkinson's disease (PD), but chronic use initiates a maladaptive process leading to l-DOPA-induced dyskinesia (LID). Risk factors for early onset LID include younger age, more severe disease at baseline and higher daily l-DOPA dose, but biomarkers to predict the risk of motor complications are not yet available. Here, we investigated whether CSF levels of catecholamines and its metabolites are altered in PD patients with LID [PD-LID, n = 8)] as compared to non-dyskinetic PD patients receiving l-DOPA (PD-L, n = 6), or not receiving l-DOPA (PD-N, n = 7) as well as non-PD controls (n = 16). PD patients were clinically assessed using the Unified Parkinson's Disease Rating Scale and Unified Dyskinesia Rating Scale and CSF was collected after overnight fasting and 1-2 h after oral intake of l-DOPA or other anti-Parkinson medication. CSF catecholamines and its metabolites were analyzed by HPLC with electrochemical detection. We observed (i) decreased levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid in PD patients not receiving l-DOPA (ii) higher dopamine (DA) levels in PD-LID as compared to controls (iii) higher DA/l-DOPA and lower DOPAC/DA ratio's in PD-LID as compared to PD-L and (iv) an age-dependent increase of DA and decrease of DOPAC/DA ratio in controls. These results suggest increased DA release from non-DA cells and deficient DA re-uptake in PD-LID. Monitoring DA and DOPAC in CSF of l-DOPA-treated PD patients may help identify patients at risk of developing LID.

Assessment of Residents Readiness to Perform Lumbar Puncture: A Validation Study.

BACKGROUND: Lumbar puncture is a common procedure in many specialties. The procedure serves to diagnose life-threatening conditions, often requiring rapid performance. However, junior doctors possess uncertainties regarding performing the procedure and frequently perform below expectations. Hence, proper training and assessment of performance is crucial before entering clinical practice. OBJECTIVE: To develop and collect validity evidence for an assessment tool for lumbar puncture performance, including a standard to determine when trainees are ready for clinical practice. DESIGN: Development of a new tool, based on clinician interviews and a literature review, was followed by an explorative study to gather validity evidence. PARTICIPANTS AND MAIN MEASURES: We interviewed 12 clinicians from different specialties. The assessment tool was used to assess 11 doctors at the advanced beginners' level and 18 novices performing the procedure in a simulated, ward-like setting with a standardized patient. Procedural performance was assessed by three content experts. We used generalizability theory to explore reliability. The discriminative ability of the tool was explored by comparing performance scores between the two groups. The contrasting groups method was used to set a pass/fail standard and the consequences of this was explored. KEY RESULTS: The interviews identified that in addition to the technical aspects of the procedure, non-technical elements involving planning and conducting the procedure are important. Cronbach's alpha = 0.92, Generalizability-coefficient was 0.88 and a Decision-study found one rater was sufficient for low-stakes assessments (G-coefficient 0.71). The discriminative ability was confirmed by a significant difference between the mean scores of novices, 40.9 (SD 6.1) and of advanced beginners, 47.8 (SD 4.0), p = 0.004. A standard of 44.0 was established which was consistent with the raters' global judgments of pass/fail. CONCLUSION: We developed and demonstrated strong validity evidence for the lumbar puncture assessment tool. The tool can be used to assess readiness for practice.