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The conventional approach to the analysis of a Phase III trial in head injury or stroke takes an ordered scale measuring functional outcome and collapses the scale to a binary outcome of favorable versus unfavorable. This discards potentially relevant information which limits statistical power and moreover is not in accord with clinical practice. We propose an alternative approach where a favorable outcome is defined as better than would be expected, taking account of each individual patient's baseline prognosis. This is illustrated through a worked example based on data from a Phase III trial in head injury. The approach is also compared with the proportional odds model, which is another statistical approach that can exploit an ordered outcome scale. The approach raises issues of clinical, statistical, and regulatory importance, and we initiate what we believe needs to become a widespread debate amongst the community involved in clinical research in head injury and stroke.

Background and Purpose-Primary intracerebral hemorrhage (ICH) accounts for 10% to 20% of stroke but carries the highest rates of mortality and morbidity of all stroke subtypes. Current treatment, however, is varied and haphazard. The most recent Cochrane systematic review refers to 4 prospective, randomized controlled trials. We present a further meta-analysis to include 3 new trials. In addition, we review the trials of Chen et al and McKissock et al and discuss aspects of their quality that, we believe, prevent their inclusion in modern day meta-analysis. Methods-Literature databases and articles were searched from 1966 to October 1999. Using the end points of death and dependency, the results of the 7 identified randomized trials were expressed as odds ratios. All available data were then analyzed with meta-analysis techniques. Analysis of relevant subsets of trials was also carried out. Results-Meta-analysis of all 7 trials shows a trend toward a higher chance of death and dependency after surgery (OR 1.20; 95% CI 0.83 to 1.74). Meta-analysis was also carried out after exclusion of the Chen and McKissock trials for reasons discussed in the text. This meta-analysis suggests a benefit from surgery, with a reduction in the chances of death and dependency after surgical treatment by a factor of 0.63 (OR 0.63; 95% CI 0.35 to 1.14). Conclusions-When meta-analysis is restricted to modern-day, post-CT, well-constructed, balanced trials, a trend for surgery to reduce the chances of death and dependency is found. Perhaps, then, in the modern era of CT, good neuroanesthesia, intensive care, and the operating microscope, surgery has a role in the treatment of supratentorial intracerebral hemorrhage. The results of a large, multicenter, randomized controlled trial are urgently needed, and the ongoing International Surgical Trial of Intracerebral Hemorrhage should fulfill this objective. (Stroke.

The aim of the study was to find out the prevalence of transfusion transmitted infections (TTI) in voluntary and replacement donors. A total of 9599 donors were analysed for the prevalence of TTI over a period of 2 years.Of these 61.2% were voluntary donors and 38.8% were replacement donors. Prevalence of TTI in total donors was 0.6%. Prevalence of hepatitis B was highest (0.34%) followed by syphilis (0.11%), HIV&HCV (0.06%) and malaria (0.01%). Prevalence was more in male replacement donors. Extensive donor selection and screening procedures will help in improving the blood safety.

This is the first study in which it is documented that some of the perilesional hypoperfused tissue around human ICH regains its perfusion in the long term, leading the authors to suggest that there may be a penumbra in human ICH. Medical or surgical therapeutic interventions could increase the volume of perilesional brain that recovers after the initial insult. The results of this study therefore support the concept that intervention in ICH has the potential to reduce the ultimate neurological deficit and improve outcome.

IntroductionMultimodality monitoring is regularly employed in adult traumatic brain injury (TBI) patients where it provides physiologic and therapeutic insight into this heterogeneous condition. Pediatric studies are less frequent.MethodsAn analysis of data collected prospectively from 12 pediatric TBI patients admitted to Addenbrooke’s Hospital, Pediatric Intensive Care Unit (PICU) between August 2012 and December 2014 was performed. Patients’ intracranial pressure (ICP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) were monitored continuously using brain monitoring software ICM+®,) Pressure reactivity index (PRx) and ‘Optimal CPP’ (CPPopt) were calculated. Patient outcome was dichotomized into survivors and non-survivors.ResultsAt 6 months 8/12 (66%) of the cohort survived the TBI. The median (±IQR) ICP was significantly lower in survivors 13.1±3.2 mm Hg compared to non-survivors 21.6±42.9 mm Hg (p = 0.003). The median time spent with ICP over 20 mm Hg was lower in survivors (9.7+9.8% vs 60.5+67.4% in non-survivors; p = 0.003). Although there was no evidence that CPP was different between survival groups, the time spent with a CPP close (within 10 mm Hg) to the optimal CPP was significantly longer in survivors (90.7±12.6%) compared with non-survivors (70.6±21.8%; p = 0.02). PRx provided significant outcome separation with median PRx in survivors being 0.02±0.19 compared to 0.39±0.62 in non-survivors (p = 0.02).ConclusionOur observations provide evidence that multi-modality monitoring may be useful in pediatric TBI with ICP, deviation of CPP from CPPopt, and PRx correlating with patient outcome.

STUDY QUESTION Does the presence of adenomyosis in women treated with IVF alter IVF outcomes? SUMMARY ANSWER Adenomyosis does not significantly alter IVF outcomes when adjusted for confounding factors including maternal age and smoking status. WHAT IS KNOWN ALREADY Studies evaluating adenomyosis and its impact on infertility, particularly when focusing on IVF, remain controversial. Many studies report that adenomyosis has a detrimental effect on IVF outcomes, however age is strongly related with both the prevalence of adenomyosis and worse reproductive outcomes. STUDY DESIGN, SIZE, DURATION A prospective cohort study of women undergoing 4002 IVF cycles who had undergone a screening ultrasound assessing features of adenomyosis from 1 January 2016 to 31 March 2018 at a multi-site private fertility clinic. Of these women, 1228 fulfilled the inclusion criteria and commenced an IVF cycle, with a subset of 715 women undergoing an embryo transfer (ET). Women were defined as having adenomyosis if there was sonographic evidence of adenomyosis on ultrasound as per the Morphological Uterus Sonographic Assessment criteria, and were then compared to women without. PARTICIPANTS/MATERIALS, SETTING, METHODS All women at a private multi-site IVF clinic who underwent a standardised ultrasound to identify features of adenomyosis and also commenced an IVF cycle were assessed for their outcomes. These included clinical pregnancy (defined as the presence of a gestational sac on ultrasound at 7 weeks’ gestation), clinical pregnancy loss, number of cancelled cycles, number of useful embryos for transfer or freezing and live birth rates. As a secondary aim, initiated stimulation cycles and those that had an ET were analysed separately to determine when an effect of adenomyosis on IVF might occur: during stimulation or transfer. MAIN RESULTS AND THE ROLE OF CHANCE When adjusting for confounders, women with and without sonographic features of adenomyosis had no significant differences in most of their IVF outcomes including live birth rates. LIMITATIONS, REASONS FOR CAUTION Adenomyosis had a detrimental impact on IVF outcomes prior to adjusting for confounding factors. No allowance was made for the possibility that confounding factors may merely reduce the effect size of adenomyosis on IVF outcomes. Second, despite a power calculation, the study was underpowered as not all fresh cycles led to an ET. WIDER IMPLICATIONS OF THE FINDINGS This is one of the largest studies to evaluate adenomyosis and IVF outcomes, while also importantly adjusting for confounding factors. The results suggest that adenomyosis does not have the detrimental impact on IVF that has previously been suggested, possibly reducing the importance of screening for and treating this entity. STUDY FUNDING/COMPETING INTEREST(S) The study received no external funding. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER ACTRN12617000796381.

Microglia, the tissue resident macrophages of the CNS, are implicated in a broad range of neurological pathologies, from acute brain injury to dementia. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single cell and bulk RNA sequencing, we defined distinct cellular populations of acutely in vivo-activated microglia, and characterised a dramatic switch in microglial population composition in patients suffering from acute brain injury. We mapped expression quantitative trait loci (eQTLs) in human microglia and show that many diseaseassociated eQTLs in microglia replicate well in a human induced pluripotent stem cell (hIPSC) derived macrophage model system. Using ATAC-seq from 95 individuals in this hIPSC model we fine-map candidate causal variants at risk loci for Alzheimer's disease, the most prevalent neurodegenerative condition in acute brain injury patients. Our study provides the first population-scale transcriptional map of a critically important cell for neurodegenerative disorders.