Emicizumab prophylaxis in haemophilia A with inhibitors: Three years follow-up from the UK Haemophilia Centre Doctors' Organisation (UKHCDO).

INTRODUCTION: The UK National Haemophilia Database (NHD) collects data from all UK persons with haemophilia A with inhibitors (PwHA-I). It is well-placed to investigate patient selection, clinical outcomes, drug safety and other issues not addressed in clinical trials of emicizumab. AIMS: To determine safety, bleeding outcomes and early effects on joint health of emicizumab prophylaxis in a large, unselected cohort using national registry and patient reported Haemtrack (HT) data between 01 January 2018 and 30 September 2021. METHODS: Prospectively collected bleeding outcomes were analysed in people with ≥6 months emicizumab HT data and compared with previous treatment if available. Change in paired Haemophilia Joint Health Scores (HJHS) were analysed in a subgroup. Adverse events (AEs) reports were collected and adjudicated centrally. RESULTS: This analysis includes 117 PwHA-I. Mean annualised bleeding rate (ABR) was .32 (95% CI, .18; .39) over a median 42 months treatment with emicizumab. Within-person comparison (n = 74) demonstrated an 89% reduction in ABR after switching to emicizumab and an increase in zero treated bleed rate from 45 to 88% (p < .01). In a subgroup of 37 people, total HJHS improved in 36%, remained stable in 46% and deteriorated in 18%, with a median (IQR) within-person change of -2.0 (-9, 1.5) (p = .04). Three arterial thrombotic events were reported, two possibly drug related. Other AEs were generally non-severe and usually limited to early treatment, included cutaneous reactions (3.6%), headaches (1.4%), nausea (2.8%) and arthralgia (1.4%). CONCLUSIONS: Emicizumab prophylaxis is associated with sustained low bleeding rates and was generally well-tolerated in people with haemophilia A and inhibitors.

A micro RNA mediates shoot control of root branching.

Plants extract mineral nutrients from the soil, or from interactions with mutualistic soil microbes via their root systems. Adapting root architecture to nutrient availability enables efficient resource utilization, particularly in patchy and dynamic environments. Root growth responses to soil nitrogen levels are shoot-mediated, but the identity of shoot-derived mobile signals regulating root growth responses has remained enigmatic. Here we show that a shoot-derived micro RNA, miR2111, systemically steers lateral root initiation and nitrogen responsiveness through its root target TML (TOO MUCH LOVE) in the legume Lotus japonicus, where miR2111 and TML were previously shown to regulate symbiotic infections with nitrogen fixing bacteria. Intriguingly, systemic control of lateral root initiation by miR2111 and TML/HOLT (HOMOLOGUE OF LEGUME TML) was conserved in the nonsymbiotic ruderal Arabidopsis thaliana, which follows a distinct ecological strategy. Thus, the miR2111-TML/HOLT regulon emerges as an essential, conserved factor in adaptive shoot control of root architecture in dicots.

Catheter-related thrombosis: A practical approach.

Catheter-related thrombosis is a relatively common complication of central venous catheter insertion. Central venous catheter use is ubiquitous in the critical care setting and often in patients with multiple risk factors for venous thromboembolism. With a trend towards increased use of peripherally inserted central catheters, the incidence of catheter-related thrombosis is likely to increase further. Despite the scale of the problem, there is a paucity of evidence-based guidelines concerning the management of patients with catheter-related thrombosis, particularly in critically unwell patients. This has led to heterogeneity in clinical practice. In this review, we describe the risk factors for developing catheter-related thrombosis and provide practical advice for clinicians on how to recognise, diagnose and treat this common problem.

Response of estuarine meio- and macrofauna to in situ bioremediation of oil-contaminated sediment.

Numerous studies have demonstrated the efficacy of bioremediation for enhancing oil removal but the ecological effect on shoreline biota is unclear. Therefore, a field experiment was designed at an intertidal sandflat in SW England to assess the effects of nutrient addition to oiled sediments on meio- and macrofauna for a period of up to 45 weeks. Natural assemblages were exposed to different types of experimental treatments (no oil, oil alone, oil treated with slow-release fertiliser or liquid fertiliser). Bioremediation stimulated the microbial population and increased oil biodegradation. This, however, did not result in faster recolonisation rates of fertilised versus non-fertilised oiled sediments. Mild effects of oil and bioremediation treatments on benthic fauna were observed, including short-term shifts in dominance patterns. Decreased abundance of dominant species in the oiled compared to unoiled sediments resulted in significantly higher evenness of benthic assemblages within the first 11 weeks of the experiment.

Ventilation strategies in burn intensive care: A retrospective observational study.

Consensus regarding optimal burns intensive care (BICU) patient management is lacking. This study aimed to assess whether ventilation strategies, cardiovascular support and sedation in BICU patients have changed over time, and whether this affects outcome. A retrospective observational study comparing two 12-patient BICU cohorts (2005/06 and 2010/11) was undertaken. Demographic and admission characteristics, ventilation parameters, sedation, fluid resuscitation, cardiovascular support and outcome (length of stay, mortality) data were collected from patient notes. Data was analysed using T-tests, Fisher's exact and Mann-Whitney U tests. In our study cohort groups were equivalent in demographic and admission parameters. There were equal ventilator-free days in the two cohorts 10 ± 12.7 vs. 13.3 ± 12.2 ventilator free days; P = 0.447). The 2005/06 cohort were mechanically ventilated more often than in 2010/11 cohort (568 ventilator days/1000 patient BICU days vs. 206 ventilator days/1000 patient BICU days; P = 0.001). The 2005/06 cohort were ventilated less commonly in tracheostomy group/endotracheal tube spontaneous (17.8% vs. 26%; P = 0.001) and volume-controlled modes (34.4% vs. 40.8%; P = 0.001). Patients in 2010/11 cohort were more heavily sedated (P = 0.001) with more long-acting sedative drug use (P = 0.001) than the 2005/06 cohort, fluid administration was equivalent. Patient outcome did not vary. Inhalational injury patients were ventilated in volume-controlled (44.5% vs. 28.1%; P = 0.001) and pressure-controlled modes (18.2% vs. 9.5%; P = 0.001) more frequently than those without. Outcome did not vary. This study showed there has been shift away from mechanical ventilation, with increased use of tracheostomy/tracheal tube airway spontaneous ventilation. Inhalation injury patients require more ventilatory support though patient outcomes do not differ. Prospective trials are required to establish which strategies confer benefit.