Coagulation profiles are associated with early clinical outcomes in neonatal encephalopathy

Introduction: Neonatal encephalopathy (NE) is associated with coagulation abnormalities. We aimed to investigate the serial alterations in coagulation profiles in term infants with NE and correlate with their clinical outcomes. This was a prospective cohort study in a tertiary referral, university-affiliated maternity hospital. Neonates exposed to perinatal asphyxia were recruited (n = 82) and 39 received therapeutic hypothermia. Infants had serial coagulation tests including platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen in the first week of life. The main outcome measures included MRI brain and EEG seizures. Our results show that mortality was predicted on day 1 by decreased Fibrinogen (AUC = 0.95, p = 0.009) and by PT on day 2 with a cutoff of 22 s. An abnormal MRI was predicted by Fibrinogen on day 3 with a cut-off value of 2 g/L. For prediction of grade II/III NE, PT on day 2 of life was strongest with a cut-off value of 14 s. Only elevated APTT levels on day 1 of life were predictive of seizures (AUC = 0.65, p = 0.04). Conclusion: Coagulation parameters are strong predictors of outcomes such as abnormal NE grade, seizures, and mortality

Dilemmas on emicizumab in children with haemophilia A: A survey of strategies from PedNet centres.

INTRODUCTION Haemophilia A care has changed with the introduction of emicizumab. Experience on the youngest children is still scarce and clinical practice varies between haemophilia treatment centres. AIM We aimed to assess the current clinical practice on emicizumab prophylaxis within PedNet, a collaborative research platform for paediatricians treating children with haemophilia. METHODS An electronic survey was sent to all PedNet members (n = 32) between October 2022 and February 2023. The survey included questions on the availability of emicizumab, on the practice of initiating prophylaxis in previously untreated or minimally treated patients (PUPs or MTPs) and emicizumab use in patients with or without inhibitors. RESULTS All but four centres (28/32; 88%) responded. Emicizumab was available in clinical practice in 25/28 centres (89%), and in 3/28 for selected patients only (e.g. with inhibitors). Emicizumab was the preferred choice for prophylaxis in PUPs or MTPs in 20/25 centres; most (85%) started emicizumab prophylaxis before 1 year of age (30% before 6 months of age) and without concomitant FVIII (16/20; 80%). After the loading dose, 13/28 centres administered the recommended dosing, while the others adjusted the interval of injections to give whole vials. In inhibitor patients, the use of emicizumab during ITI was common, with low-dose ITI being the preferred protocol. CONCLUSION Most centres choose to initiate prophylaxis with emicizumab before 12 months of age and without concomitant FVIII. In inhibitor patients, ITI is mostly given in addition to emicizumab, but there was no common practice on how to proceed after successful ITI

Bleeding control improves after switching to emicizumab: Real-world experience of 177 children in the PedNet registry

Introduction: Despite the rapid uptake of emicizumab in the paediatric haemophilia A (HA) population, real-world data on the safety and efficacy is limited. Aim: To report on bleeding and safety in paediatric patients receiving emicizumab prophylaxis. Methods: Data were extracted from the multicentre prospective observational PedNet Registry (NCT02979119). Children with haemophilia A, and ≥50 FVIII exposures or inhibitors present receiving emicizumab maintenance therapy were analysed. Data were summarized as medians with interquartile range (IQR, P25–P75). Mean (95% confidence interval (CI)), annualized (joint) bleeding rate (A(J)BR) during emicizumab and ≤2 years before emicizumab prophylaxis were modelled and compared using negative binomial regression. Results: Total of 177 patients started emicizumab at median 8.6 years (IQR 4.8–13.1), most had no FVIII inhibitors (64%). Follow up before emicizumab was median: 1.68 years (IQR: 1.24–1.90) and during emicizumab: 1.32 years (IQR:.94–2.11). In patients without inhibitors, mean ABR reduced after starting emicizumab from 2.41 (CI 1.98–2.95) to 1.11 (CI.90–1.36, p <.001), while AJBR reduced from.74 (CI.56–.98) to.31 (CI.21–.46, p <.001). Concordantly, in patients with inhibitors, mean ABR reduced from 5.08 (CI 4.08–6.38) to.75 (CI.56–1.01, p <.001), while AJBR reduced from 1.90 (CI 1.42–2.58) to.34 (CI.21–.56, p <.001). Five emicizumab-related adverse events were reported (3% of the cohort), including one patient with antidrug antibodies. Conclusion: This study showed improved bleeding control compared to previous treatment and a favourable safety profile during emicizumab therapy in paediatric haemophilia A patients. Trial registration: Clin.gov.trial-NCT02979119

Dilemmas on emicizumab in children with haemophilia A: A survey of strategies from PedNet centres

INTRODUCTION: Haemophilia A care has changed with the introduction of emicizumab. Experience on the youngest children is still scarce and clinical practice varies between haemophilia treatment centres. AIM: We aimed to assess the current clinical practice on emicizumab prophylaxis within PedNet, a collaborative research platform for paediatricians treating children with haemophilia. METHODS: An electronic survey was sent to all PedNet members (n = 32) between October 2022 and February 2023. The survey included questions on the availability of emicizumab, on the practice of initiating prophylaxis in previously untreated or minimally treated patients (PUPs or MTPs) and emicizumab use in patients with or without inhibitors. RESULTS: All but four centres (28/32; 88%) responded. Emicizumab was available in clinical practice in 25/28 centres (89%), and in 3/28 for selected patients only (e.g. with inhibitors). Emicizumab was the preferred choice for prophylaxis in PUPs or MTPs in 20/25 centres; most (85%) started emicizumab prophylaxis before 1 year of age (30% before 6 months of age) and without concomitant FVIII (16/20; 80%). After the loading dose, 13/28 centres administered the recommended dosing, while the others adjusted the interval of injections to give whole vials. In inhibitor patients, the use of emicizumab during ITI was common, with low-dose ITI being the preferred protocol. CONCLUSION: Most centres choose to initiate prophylaxis with emicizumab before 12 months of age and without concomitant FVIII. In inhibitor patients, ITI is mostly given in addition to emicizumab, but there was no common practice on how to proceed after successful ITI

Long-term safety and efficacy of extended-interval prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) in subjects with haemophilia B

The safety, efficacy, and prolonged half-life of recombinant factor IX Fc fusion protein (rFIXFc) were demonstrated in the Phase 3 B-LONG (adults/adolescents ≥12 years) and Kids B-LONG (children <12 years) studies of subjects with haemophilia B (≤2 IU/dl). Here, we report interim, long-term safety and efficacy data from B-YOND, the rFIXFc extension study. Eligible subjects who completed B-LONG or Kids B-LONG could enrol in B-YOND. There were four treatment groups: weekly prophylaxis (20–100 IU/kg every 7 days), individualised prophylaxis (100 IU/kg every 8–16 days), modified prophylaxis (further dosing personalisation to optimise prophylaxis), and episodic (on-demand) treatment. Subjects could change treatment groups at any point. Primary endpoint was inhibitor development. One hundred sixteen subjects enrolled in B-YOND. From the start of the parent studies to the B-YOND interim data cut, median duration of rFIXFc treatment was 39.5 months and 21.9 months among adults/adolescents and children, respectively; 68/93 (73.1 %) adults/adolescents and 9/23 (39.1 %) children had ≥100 cumulative rFIXFc exposure days. No inhibitors were observed. Median annualised bleeding rates (ABRs) were low in all prophylaxis regimens: weekly (≥12 years: 2.3; <6 years: 0.0; 6 to <12 years: 2.7), individualised (≥12 years: 2.3; 6 to <12 years: 2.4), and modified (≥12 years: 2.4). One or two infusions were sufficient to control 97 % (adults/adolescents) and 95 % (children) of bleeding episodes. Interim data from B-YOND are consistent with data from B-LONG and Kids B-LONG, and confirm the long-term safety of rFIXFc, absence of inhibitors, and maintenance of low ABRs with prophylactic dosing every 1 to 2 weeks

The First Data Release of the Sloan Digital Sky Survey

The Sloan Digital Sky Survey has validated and made publicly available its First Data Release. This consists of 2099 square degrees of five-band (u, g, r, i, z) imaging data, 186,240 spectra of galaxies, quasars, stars and calibrating blank sky patches selected over 1360 square degrees of this area, and tables of measured parameters from these data. The imaging data go to a depth of r ~ 22.6 and are photometrically and astrometrically calibrated to 2% rms and 100 milli-arcsec rms per coordinate, respectively. The spectra cover the range 3800--9200 A, with a resolution of 1800--2100. Further characteristics of the data are described, as are the data products themselves.Comment: Submitted to The Astronomical Journal. 16 pages. For associated documentation, see http://www.sdss.org/dr

Correction of haemostasis can be reduced to four days for CVAD implantation in severe haemophilia A patients: Data from the PedNet study group.

INTRODUCTION Central venous access devices (CVAD) are used to facilitate intravenous treatment with coagulation factor concentrates (CFCs) in haemophilia A (HA). Guidelines for perioperative CFC replacement therapy are based on single centre experiences, and the length of replacement therapy varies. AIM The aim of this study was to evaluate whether haemostasis coverage under four days is as effective and safe as a longer period of haemostatic coverage. METHODS We identified patients with severe HA without inhibitors or major bleeds within one month of the surgery who received their first CVAD. We compared the CFC consumption and bleeds between children with ≤4 and those who received 5-7 perioperative treatment days including the day of surgery. Bleeds were recorded up to 4 days after the end of perioperative haemostatic coverage. RESULTS In total, 144 children met the eligibility criteria and were included in the study cohort: 34 had received haemostatic coverage for ≤4 days, while 110 had received 5-7 days of haemostatic coverage. One bleed related to the surgery occurred in both groups. CONCLUSION Overall, the bleeding complications were rare. Haemostatic coverage with CFCs under ≤4 days with elective CVAD insertions was as effective as coverage for ≥5 days

Valuing Victoria Business Improvement District's Urban Forest - a comparison of methodologies

There are more than 200 Business Improvement Districts (BIDs) operating across the United Kingdom. A BID is a business‐led and business funded body formed to improve a defined commercial area. Several BIDs in the UK have either already developed their green infrastructure plans or are currently looking at similar audits. The Victoria BID in London, was the first to carry out an audit and this has led to significant interest and investment in environmental improvements in the area. More recently 14 other London BIDs have completed their audits. The two Liverpool BIDs and Northwich BID in Cheshire, have also carried out their audit and are due to publish their Green Infrastructure Prospectus in summer 2016. Victoria BID’s Green Audit identified the importance of the urban forest. The population of mature trees, mainly London Plane (Platanus × acerifolia) providing a wide range of benefits for the BID area. Itree was used to assess the economic value of the urban forest. However, for the non‐tree green infrastructure elements the GI‐Val toolkit was used. As part of the EU Cost Action IP1204 "GreenInUrbs", further work has been carried out to look at the use of itree and GI‐Val. The results showed that the itree provided more detailed data that could not only be used to establish the economic value of the urban forest, and inform detailed management planning. However, data capture was expensive and time consuming. GI‐Val in contrast provided less detailed data on the green infrastructure resource, provided a wider range of tools and values, and took significantly less resource to gather and analyze data. GI‐Val also was able to provide data on a wider range of green infrastructure typologies than itree. However, the results provided less accurate data on the economic value of the green infrastructure

Fitusiran Prophylaxis Improves Health-Related Quality of Life in People with Hemophilia a or B, with or without Inhibitors: Results of ATLAS-PPX Study

[No Abstract Available