Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial

Item does not contain fulltextBACKGROUND: Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the extent of the haemorrhage. We aimed to investigate whether platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral haemorrhage associated with antiplatelet therapy use. METHODS: We did this multicentre, open-label, masked-endpoint, randomised trial at 60 hospitals in the Netherlands, UK, and France. We enrolled adults within 6 h of supratentorial intracerebral haemorrhage symptom onset if they had used antiplatelet therapy for at least 7 days beforehand and had a Glasgow Coma Scale score of at least 8. With use of a secure web-based system that concealed allocation and used biased coin randomisation, study collaborators randomly assigned participants (1:1; stratified by hospital and type of antiplatelet therapy) to receive either standard care or standard care with platelet transfusion within 90 min of diagnostic brain imaging. Participants and local investigators giving interventions were not masked to treatment allocation, but allocation was concealed from outcome assessors and investigators analysing data. The primary outcome was shift towards death or dependence rated on the modified Rankin Scale (mRS) at 3 months, and analysed by ordinal logistic regression, adjusted for stratification variables and the Intracerebral Haemorrhage Score. The primary analysis was done in the intention-to-treat population and safety analyses were done in the intention-to-treat and as-treated populations. This trial is registered with the Netherlands Trial Register, number NTR1303, and is now closed. FINDINGS: Between Feb 4, 2009, and Oct 8, 2015, 41 sites enrolled 190 participants. 97 participants were randomly assigned to platelet transfusion and 93 to standard care. The odds of death or dependence at 3 months were higher in the platelet transfusion group than in the standard care group (adjusted common odds ratio 2.05, 95% CI 1.18-3.56; p=0.0114). 40 (42%) participants who received platelet transfusion had a serious adverse event during their hospital stay, as did 28 (29%) who received standard care. 23 (24%) participants assigned to platelet transfusion and 16 (17%) assigned to standard care died during hospital stay. INTERPRETATION: Platelet transfusion seems inferior to standard care for people taking antiplatelet therapy before intracerebral haemorrhage. Platelet transfusion cannot be recommended for this indication in clinical practice. FUNDING: The Netherlands Organisation for Health Research and Development, Sanquin Blood Supply, Chest Heart and Stroke Scotland, French Ministry of Health

Study protocol training for life: a stepped wedge cluster randomized trial about emergency obstetric simulation-based training in a low-income country

Abstract Background Globally perinatal and maternal mortality rates remain unacceptably high. There is increasing evidence that simulation-based training in obstetric emergencies is associated with improvement in clinical outcomes. However, the results are not entirely consistent. The need for continued research in a wide variety of clinical settings to establish what works, where and why was recommended. The aim of this study is to investigate the effectiveness of an emergency obstetric simulation-based training program with medical technical and teamwork skills on maternal and perinatal mortality in a low-income country. Methods A stepped wedge cluster randomized trial will be conducted at the medium to high-risk labour ward at Mulago Hospital, Kampala, Uganda, with an annual delivery rate of over 23,000. The training will be performed using a train-the-trainers model in which training is cascaded down from master trainers to local facilitators (gynaecologists) to learners (senior house officers). Local facilitators will be trained during a four-day train-the-trainers course with an annual repetition. The senior house officers will be naturally divided in seven clusters and randomized for the moment of training. The training consists of a one-day, monodisciplinary, simulation-based training followed by repetition training sessions. Scenarios are based on the main local causes of maternal and neonatal mortality and focus on both medical technical and crew resource management skills. Kirkpatrick’s classification will be used to evaluate the training program. Primary outcome will be the composite of maternal and neonatal mortality ratios. Secondary outcome will comprise course perception, evaluation of the instructional design of the training, knowledge, technical skills, team performance, percentage of ventouse deliveries, percentage of caesarean sections, and a Weighted Adverse Outcome Score. Discussion This stepped wedge cluster randomized trial will investigate the effect of a monodisciplinary simulation-based obstetric training in a low-income country, focusing on both medical technical skills and crew resource management skills, on patient outcome at one of the largest labour wards worldwide. We will use a robust study design which will allow us to better understand the training effects, and difficulties in evaluating training programs in low-income countries. Trial registration ISRCTN98617255 , retrospectively registered July 23, 2018

Intra- and interindividual attack frequency variability of chronic cluster headache

BackgroundThe lack of knowledge about the intra- and interindividual attack frequency variability in chronic cluster headache complicates power and sample size calculations for baseline periods of trials, and consensus on their most optimal duration.MethodsWe analyzed the 12-week baseline of the ICON trial (occipital nerve stimulation in medically intractable chronic cluster headache) for: (i) weekly vs. instantaneous recording of attack frequency; (ii) intra-individual and seasonal variability of attack frequency; and (iii) the smallest number of weeks to obtain a reliable estimate of baseline attack frequency.ResultsWeekly median (14.4 [8.2–24.0]) and instantaneous (14.2 [8.0–24.5]) attack frequency recordings were similar (p = 0.20; Bland-Altman plot). Median weekly attack frequency was 15.3 (range 4.2–140) and highest during spring (p = 0.001) compared to the other seasons. Relative attack frequency variability decreased with increasing attack frequency (p = 0.010). We tabulated the weekly attack frequency estimation accuracies compared to, and the associated deviations from, the 12-week gold standard for different lengths of the observation period.ConclusionWeekly retrospective attack frequency recording is as good as instantaneous recording and more convenient. Attack frequency is highest in spring. Participants with ≥3 daily attacks show less attack frequency variability than those wit