Assessing behavioural changes in ALS: cross-validation of ALS-specific measures

Objective: The Beaumont Behavioural Inventory (BBI) is a behavioural proxy report for the assessment of behavioural changes in ALS. This tool has been validated against the FrSBe, a non-ALS specific behavioural assessment, and further comparison of the BBI against a disease-specific tool was considered. This study cross-validates the BBI against the ALS-FTD-Q. Methods: 60 ALS patients, 8% also meeting criteria for FTD, were recruited. All patients were evaluated using the BBI and the ALS-FTD-Q, completed by a carer. Correlational analysis was performed to assess construct validity. Precision, sensitivity, specificity and overall accuracy of the BBI, when compared to the ALS-FTD-Q, were obtained. Results: The mean score of the whole sample on the BBI was 11.45±13.06. ALS-FTD patients scored significantly higher than non-demented ALS patients (31.6±14.64, 9.62±11.38; p<.0001). A significant large positive correlation between the BBI and the ALS-FTD-Q was observed (r=.807, p<.0001), and no significant correlations between the BBI and other clinical/demographic characteristics, indicating good convergent and discriminant validity, respectively. 72% of overall concordance was observed. Precision, sensitivity and specificity for the classification of severely impaired patients were adequate. However, lower concordance in the classification of mild behavioural changes was observed, with higher sensitivity using the BBI, most likely secondary to BBI items which endorsed behavioural aspects not measured by the ALS-FTD-Q. Discussion: Good construct validity has been further confirmed when the BBI is compared to an ALS-specific tool. Furthermore, the BBI is a more comprehensive behavioural assessment for ALS, as it measures the whole behavioural spectrum in this condition

Re-evaluating syndicalist opposition to the First World War

It has been argued that support for the First World War by the important French syndicalist organisation, the Confédération Générale du Travail (CGT) has tended to obscure the fact that other national syndicalist organisations remained faithful to their professed workers’ internationalism: on this basis syndicalists beyond France, more than any other ideological persuasion within the organised trade union movement in immediate pre-war and wartime Europe, can be seen to have constituted an authentic movement of opposition to the war in their refusal to subordinate class interests to those of the state, to endorse policies of ‘defencism’ of the ‘national interest’ and to abandon the rhetoric of class conflict. This article, which attempts to contribute to a much neglected comparative historiography of the international syndicalist movement, re-evaluates the syndicalist response across a broad geographical field of canvas (embracing France, Italy, Spain, Ireland, Britain and America) to reveal a rather more nuanced, ambiguous and uneven picture. While it highlights the distinctive nature of the syndicalist response compared with other labour movement trends, it also explores the important strategic and tactical limitations involved, including the dilemma of attempting to translate formal syndicalist ideological commitments against the war into practical measures of intervention, and the consequences of the syndicalists’ subordination of the political question of the war to the industrial struggle

A randomized, double-blind, placebo-controlled trial of intravenous alpha-1 antitrypsin for ARDS secondary to COVID-19

Background: Patients with severe coronavirus disease 2019 (COVID-19) develop a febrile pro-inflammatory cytokinemia with accelerated progression to acute respiratory distress syndrome (ARDS). Here we report the results of a phase 2, multicenter, randomized, double-blind, placebo-controlled trial of intravenous (IV) plasma-purified alpha-1 antitrypsin (AAT) for moderate to severe ARDS secondary to COVID-19 (EudraCT 2020-001391-15).  Methods: Patients (n = 36) were randomized to receive weekly placebo, weekly AAT (Prolastin, Grifols, S.A.; 120 mg/kg), or AAT once followed by weekly placebo. The primary endpoint was the change in plasma interleukin (IL)-6 concentration at 1 week. In addition to assessing safety and tolerability, changes in plasma levels of IL-1β, IL-8, IL-10, and soluble tumor necrosis factor receptor 1 (sTNFR1) and clinical outcomes were assessed as secondary endpoints.  Findings: Treatment with IV AAT resulted in decreased inflammation and was safe and well tolerated. The study met its primary endpoint, with decreased circulating IL-6 concentrations at 1 week in the treatment group. This was in contrast to the placebo group, where IL-6 was increased. Similarly, plasma sTNFR1 was substantially decreased in the treatment group while remaining unchanged in patients receiving placebo. IV AAT did not definitively reduce levels of IL-1β, IL-8, and IL-10. No difference in mortality or ventilator-free days was observed between groups, although a trend toward decreased time on ventilator was observed in AAT-treated patients.  Conclusions: In patients with COVID-19 and moderate to severe ARDS, treatment with IV AAT was safe, feasible, and biochemically efficacious. The data support progression to a phase 3 trial and prompt further investigation of AAT as an anti-inflammatory therapeutic.  Funding: ECSA-2020-009; Elaine Galwey Research Bursary.</p