Assessment scales in stroke: clinimetric and clinical considerations

As stroke care has developed, there has been a need to robustly assess the efficacy of interventions both at the level of the individual stroke survivor and in the context of clinical trials. To describe stroke-survivor recovery meaningfully, more sophisticated measures are required than simple dichotomous end points, such as mortality or stroke recurrence. As stroke is an exemplar disabling long-term condition, measures of function are well suited as outcome assessment. In this review, we will describe functional assessment scales in stroke, concentrating on three of the more commonly used tools: the National Institutes of Health Stroke Scale, the modified Rankin Scale, and the Barthel Index. We will discuss the strengths, limitations, and application of these scales and use the scales to highlight important properties that are relevant to all assessment tools. We will frame much of this discussion in the context of "clinimetric" analysis. As they are increasingly used to inform stroke-survivor assessments, we will also discuss some of the commonly used quality-of-life measures. A recurring theme when considering functional assessment is that no tool suits all situations. Clinicians and researchers should chose their assessment tool based on the question of interest and the evidence base around clinimetric properties

Insights into the high-energy γ-ray emission of Markarian 501 from extensive multifrequency observations in the Fermi era

We report on the γ-ray activity of the blazar Mrk 501 during the first 480 days of Fermi operation. We find that the average Large Area Telescope (LAT) γ-ray spectrum of Mrk 501 can be well described by a single power-law function with a photon index of 1.78 ± 0.03. While we observe relatively mild flux variations with the Fermi-LAT (within less than a factor of two), we detect remarkable spectral variability where the hardest observed spectral index within the LAT energy range is 1.52 ± 0.14, and the softest one is 2.51 ± 0.20. These unexpected spectral changes do not correlate with the measured flux variations above 0.3 GeV. In this paper, we also present the first results from the 4.5 month long multifrequency campaign (2009 March 15-August 1) on Mrk 501, which included the Very Long Baseline Array (VLBA), Swift, RXTE, MAGIC, and VERITAS, the F-GAMMA, GASP-WEBT, and other collaborations and instruments which provided excellent temporal and energy coverage of the source throughout the entire campaign. The extensive radio to TeV data set from this campaign provides us with the most detailed spectral energy distribution yet collected for this source during its relatively low activity. The average spectral energy distribution of Mrk 501 is well described by the standard one-zone synchrotron self-Compton (SSC) model. In the framework of this model, we find that the dominant emission region is characterized by a size ≲0.1 pc (comparable within a factor of few to the size of the partially resolved VLBA core at 15-43 GHz), and that the total jet power (≃1044 erg s-1) constitutes only a small fraction (∼10-3) of the Eddington luminosity. The energy distribution of the freshly accelerated radiating electrons required to fit the time-averaged data has a broken power-law form in the energy range 0.3 GeV-10 TeV, with spectral indices 2.2 and 2.7 below and above the break energy of 20 GeV. We argue that such a form is consistent with a scenario in which the bulk of the energy dissipation within the dominant emission zone of Mrk 501 is due to relativistic, proton-mediated shocks. We find that the ultrarelativistic electrons and mildly relativistic protons within the blazar zone, if comparable in number, are in approximate energy equipartition, with their energy dominating the jet magnetic field energy by about two orders of magnitude. © 2011. The American Astronomical Society

Prestroke modified Rankin stroke scale has moderate interobserver reliability and validity in an acute stroke setting

<br>Background and Purpose—The modified Rankin Scale (mRS) is the recommended functional outcome assessment in stroke trials. Utility of mRS may be limited by interobserver variability. prestroke function, described using mRS, is often used as trial entry criterion. We assessed the reliability and validity of prestroke mRS in acute stroke.</br> <br>Methods—We present two complementary analyses of the properties of prestroke mRS: (1) Paired interviewers (trained in mRS) performed independently a blinded assessment of mRS and prestroke mRS. Interobserver variability was described using percentage agreement and weighted (kw) κ statistics with 95% confidence interval (95% CI). Validity was assessed by comparing prestroke mRS with other markers of function (comorbidity; medication count; need for carers). (2) We further assessed validity using a larger retrospective dataset. We compared prestroke mRS with Charlson comorbidity index (CCI) and the Rockwood frailty index. Rank correlation coefficient or Fisher exact test were used as appropriate.</br> <br>Results—Paired interviewers assessed 74 stroke survivors. Median standard mRS was 4 (interquartile range [IQR], 2–4), median prestroke mRS was 1 (IQR, 0–3; range, 0–4). Reliability for standard mRS interview was 56% agreement, kw=0.55 (95% CI, 0.39–0.71). Reliability for prestroke mRS was 70%, kw=0.70 (95% CI, 0.53–0.87). The retrospective dataset described 231 subjects. In this data set, Spearman Rho for prestroke mRS and frailty index was J. 0.82 (95% CI, 0.78–0.86); CCI 0.50 (95% CI, 0.40–0.59); patient age 0.45 (95% CI, 0.34–0.54); medication count 0.28 (95% CI, 0.15–0.40). There was no association between need for carers and prestroke mRS (p=0.10).</br> <br>Conclusions—Interobserver reliability of prestroke mRS is limited but comparable with standard mRS. Poor correlation of prestroke mRS with certain markers of function suggests limited validity. Our data would suggest that relying on mRS alone may be a suboptimal measure of prestroke function and could potentially bias trial samples.</br&gt

Improving the efficiency of stroke trials: feasibility and efficacy of group adjudication of functional end points

<p>Background and Purpose — Use of the modified Rankin scale (mRS) in multicenter trials may be limited by interobserver variability. We assessed the effect of this on trial power and developed a novel group adjudication approach.</p> <p>Methods — We generated power and sample size estimates from simulated trials modeled with varying mRS reliability. We conducted a virtual acute stroke trial across 14 UK sites to develop a group adjudication approach. Traditional mRS interviews, performed at local sites, were digitally recorded and scored by adjudication committee. We assessed the effect of translation by comparing scores in translated mRS interviews, originally conducted in English and Mandarin. Agreement was measured using κ and weighted κ (κw) statistics and intraclass correlation coefficient.</p> <p>Results — Statistical simulations suggest that improving mRS reliability from κ=0.25 to κ=0.5 or 0.7 may allow reductions in sample size of n=386 or 490 in a typical n=2000 study. Our virtual acute stroke trial included 370 participants and 563 mRS video assessments. We adjudicated mRS in 538 of 563 (96%) study visits. At 30 and 90 days, 161 of 280 (57.5%) and 131 of 258 (50.8%) clips showed interobserver disagreement. Agreement within the adjudication committee was good (30-day κw=0.85 [95% confidence interval, 0.81–0.86]; 90-day κw=0.86 [95% confidence interval, 0.82–0.88]) without significant or systematic bias in mRS scoring compared with the local mRS. Interobserver reliability of translated mRS assessments was similar to native language clips (native [n=69] κw=0.91 [95% confidence interval, 0.94–0.99]; translated [n=89] κw=0.90 [95% confidence interval, 0.83–0.96]).</p> <p>Conclusions — Achievable improvements in interobserver reliability may substantially reduce study sample size, with associated financial benefits. Central adjudication of mRS assessments is feasible (including across international centers), valid and reliable despite the challenges of mRS assessment in large clinical trials.</p&gt