A note on deficit analysis in dependency models involving Coxian claim amounts

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Intracerebral implantation of human neural stem cells and motor recovery after stroke: multicentre prospective single-arm study (PISCES-2)

Background Human neural stem cell implantation may offer improved recovery from stroke. We investigated the feasibility of intracerebral implantation of the allogeneic human neural stem cell line CTX0E03 in the subacute—chronic recovery phase of stroke and potential measures of therapeutic response in a multicentre study. Methods We undertook a prospective, multicentre, single-arm, open-label study in adults aged >40 years with significant upper limb motor deficits 2–13 months after ischaemic stroke. 20 million cells were implanted by stereotaxic injection to the putamen ipsilateral to the cerebral infarct. The primary outcome was improvement by 2 or more points on the Action Research Arm Test (ARAT) subtest 2 at 3 months after implantation. Findings Twenty-three patients underwent cell implantation at eight UK hospitals a median of 7 months after stroke. One of 23 participants improved by the prespecified ARAT subtest level at 3 months, and three participants at 6 and 12 months. Improvement in ARAT was seen only in those with residual upper limb movement at baseline. Transient procedural adverse effects were seen, but no cell-related adverse events occurred up to 12 months of follow-up. Two deaths were unrelated to trial procedures. Interpretation Administration of human neural stem cells by intracerebral implantation is feasible in a multicentre study. Improvements in upper limb function occurred at 3, 6 and 12 months, but not in those with absent upper limb movement at baseline, suggesting a possible target population for future controlled trials. Funding ReNeuron, Innovate UK (application no 32074-222145). Trial registration number EudraCT Number: 2012-003482-1

Publication Bias in Reports of Animal Stroke Studies Leads to Major Overstatement of Efficacy

Publication bias confounds attempts to use systematic reviews to assess the efficacy of various interventions tested in experiments modelling acute ischaemic stroke, leading to a 30% overstatement of efficacy of interventions tested in animals

'Drowning in here in his bloody sea' : exploring TV cop drama's representations of the impact of stress in modern policing

The Criminal Justice System is a part of society that is both familiar and hidden. It is familiar in that a large part of daily news and television drama is devoted to it (Carrabine, 2008; Jewkes, 2011). It is hidden in the sense that the majority of the population have little, if any, direct contact with the Criminal Justice System, meaning that the media may be a major force in shaping their views on crime and policing (Carrabine, 2008). As Reiner (2000) notes, the debate about the relationship between the media, policing, and crime has been a key feature of wider societal concerns about crime since the establishment of the modern police force. He outlines the recurring themes in post-war debates in this field. For Conservatives there has been an ongoing concern that the media is criminongenic, as it serves to undermine traditional institutions, including the police. From the viewpoint of radical criminology, the impact of the media is two-fold: it exaggerates legitimate concerns about crime and emphasises the bureaucratic and other restrictions under which the police operate (Reiner, 2000). This is seen as undermining due process and legitimatising what can be termed a ‘maverick’ approach to policing. An early example of this can be seen in Clint Eastwood’s Dirty Harry movies (Siegel, 1971) where Harry Callaghan acts as a one-man law enforcement system outside of the formal legal process, a process portrayed as corrupt, inefficient, and concerned with offenders’ rights rather than protecting victims. From a policing perspective, Reiner (2000) argues that film and TV drama creates a simplistic narrative of crime solving that is almost completely divorced from the reality of modern police work, a finding consistent with more recent work by Cummins et al., (2014)

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice