Birmingham's Evangelical free churches and the First World War

This thesis demonstrates that the First World War did not have a major long-term impact on the evangelical free churches of Birmingham. Whilst many members were killed in the conflict, and local church auxiliaries were disrupted, once the participants – civil and military – returned, the work and mission of the churches mostly continued as they had before the conflict, the exception being the Adult School movement, which had been in decline prior to the conflict. It reveals impacts on local church life, including new opportunities for women amongst the Baptist and Congregational churches where they began to serve as deacons. The advent of conscription forced church members to personally face the issue as to whether as Christians they could in conscience bear arms. The conflict also speeded ecumenical co-operation nationally, in areas such as recognition of chaplains, and locally, in organising local prayer meetings and commemorations. The close of the conflict galvanised support for the League of Nations and for international co-operation which had been interrupted by the conflict. It has shown evidence of combatants and non-combatants alike being sustained through the conflict by their faith. Responses to the conflict varied from enthusiastic support to absolute opposition

The implications of outcome truncation in reproductive medicine RCTs: a simulation platform for trialists and simulation study.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-08-01, epub 2021-08-06Publication status: PublishedFunder: Wellcome Trust; Grant(s): 204796/Z/16/ZBackgroundRandomised controlled trials in reproductive medicine are often subject to outcome truncation, where the study outcomes are only defined in a subset of the randomised cohort. Examples include birthweight (measurable only in the subgroup of participants who give birth) and miscarriage (which can only occur in participants who become pregnant). These outcomes are typically analysed by making a comparison between treatment arms within the subgroup (for example, comparing birthweights in the subgroup who gave birth or miscarriages in the subgroup who became pregnant). However, this approach does not represent a randomised comparison when treatment influences the probability of being observed (i.e. survival). The practical implications of this for the design and interpretation of reproductive trials are unclear however.MethodsWe developed a simulation platform to investigate the implications of outcome truncation for reproductive medicine trials. We used this to perform a simulation study, in which we considered the bias, type 1 error, coverage, and precision of standard statistical analyses for truncated continuous and binary outcomes. Simulation settings were informed by published assisted reproduction trials.ResultsIncreasing treatment effect on the intermediate variable, strength of confounding between the intermediate and outcome variables, and the presence of an interaction between treatment and confounder were found to adversely affect performance. However, within parameter ranges we would consider to be more realistic, the adverse effects were generally not drastic. For binary outcomes, the study highlighted that outcome truncation could cause separation in smaller studies, where none or all of the participants in a study arm experience the outcome event. This was found to have severe consequences for inferences.ConclusionWe have provided a simulation platform that can be used by researchers in the design and interpretation of reproductive medicine trials subject to outcome truncation and have used this to conduct a simulation study. The study highlights several key factors which trialists in the field should consider carefully to protect against erroneous inferences. Standard analyses of truncated binary outcomes in small studies may be highly biassed, and it remains to identify suitable approaches for analysing data in this context

Antibiotic Class and Outcome in Post-stroke Infections: An Individual Participant Data Pooled Analysis of VISTA-Acute

Antibiotics; Post-stroke infections; Post-stroke pneumoniaAntibiòtics; Infeccions posteriors a un accident cerebrovascular; Pneumònia posterior a un accident cerebrovascularAntibióticos; Infecciones posteriores a un accidente cerebrovascular; Neumonía posterior a un accidente cerebrovascularIntroduction: Antibiotics used to treat post-stroke infections have differing antimicrobial and anti-inflammatory effects. Our aim was to investigate whether antibiotic class was associated with outcome after post-stroke infection. Methods: We analyzed pooled individual participant data from the Virtual International Stroke Trials Archive (VISTA)-Acute. Patients with ischemic stroke and with an infection treated with systemic antibiotic therapy during the first 2 weeks after stroke onset were eligible. Antibiotics were grouped into eight classes, according to antimicrobial mechanism and prevalence. The primary analysis investigated whether antibiotic class for any infection, or for pneumonia, was independently associated with a shift in 90 day modified Rankin Scale (mRS) using ordinal logistic regression. Results: 2,708 patients were eligible (median age [IQR] = 74 [65 to 80] y; 51% female; median [IQR] NIHSS score = 15 [11 to 19]). Pneumonia occurred in 35%. Treatment with macrolides (5% of any infections; 9% of pneumonias) was independently associated with more favorable mRS distribution for any infection [OR (95% CI) = 0.59 (0.42 to 0.83), p = 0.004] and for pneumonia [OR (95% CI) = 0.46 (0.29 to 0.73), p = 0.001]. Unfavorable mRS distribution was independently associated with treatment of any infection either with carbapenems, cephalosporins or monobactams [OR (95% CI) = 1.62 (1.33 to 1.97), p < 0.001], penicillin plus β-lactamase inhibitors [OR (95% CI) = 1.26 (1.03 to 1.54), p = 0.025] or with aminoglycosides [OR (95% CI) = 1.73 (1.22 to 2.46), p = 0.002]. Conclusion: This retrospective study has several limitations including effect modification and confounding by indication. Macrolides may have favorable immune-modulatory effects in stroke-associated infections. Prospective evaluation of the impact of antibiotic class on treatment of post-stroke infections is warranted.The Open Access Publication Fund of Charité—Universitätsmedizin Berlin and Professor Meisel as corresponding author will provide funding to cover the open access publication/article processing fe

Phase II randomised, placebo-controlled, clinical trial of interleukin-1 receptor antagonist in intracerebral haemorrhage: BLOcking the Cytokine IL-1 in ICH (BLOC-ICH)

PURPOSE: Recombinant human interleukin-1 receptor antagonist (anakinra) is an anti-inflammatory with efficacy in animal models of stroke. We tested the effect of anakinra on perihaematomal oedema in acute intracerebral haemorrhage (ICH) and explored effects on inflammatory markers. METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled trial in patients with acute, spontaneous, supratentorial ICH between May 2019 and February 2021. Patients were randomised to 100 mg subcutaneous anakinra within 8 h of onset, followed by five, 12-hourly, 100 mg subcutaneous injections, or matched placebo. Primary outcome was oedema extension distance (OED) on a 72 h CT scan. Secondary outcomes included plasma C-reactive protein (CRP) and interleukin-6 (IL-6). FINDINGS: 25 patients (target = 80) were recruited, 14 randomised to anakinra, 11 to placebo. Mean age was 67 and 52% were male. The anakinra group had higher median baseline ICH volume (12.6 ml, interquartile range[IQR]:4.8-17.9) versus placebo (5.5 ml, IQR:2.1-10.9). Adjusting for baseline, 72 h OED was not significantly different between groups (mean difference OED anakinra vs placebo -0.05 cm, 95% confidence interval [CI]: -0.17-0.06, p = 0.336). There was no significant difference in area-under-the-curve to Day 4 for IL-6 and CRP, but a post-hoc analysis demonstrated IL-6 was 56% (95% CI: 2%-80%) lower at Day 2 with anakinra. There were 10 and 2 serious adverse events in anakinra and placebo groups, respectively, none attributed to anakinra. CONCLUSION: We describe feasibility for delivering anakinra in acute ICH and provide preliminary safety data. We lacked power to test for effects on oedema thus further trials will be required