• Early changes in visuospatial episodic memory can help distinguish primary age‐related tauopathy from Alzheimer’s disease

      Robinson, Andrew C.; orcid: 0000-0003-2208-7728; email: andrew.c.robinson@manchester.ac.uk; Davidson, Yvonne S.; Roncaroli, Federico; orcid: 0000-0003-3650-5572; Minshull, James; Tinkler, Phillip; Horan, Michael A.; Payton, Antony; Pendleton, Neil; Mann, David M. A. (2021-05-29)
    • Early Inflammatory Cytokine Expression in Cerebrospinal Fluid of Patients with Spontaneous Intraventricular Hemorrhage

      Ziai, Wendy C.; email: weziai@jhmi.edu; Parry-Jones, Adrian R.; email: adrian.parry-jones@manchester.ac.uk; Thompson, Carol B.; email: cthomp45@jhu.edu; Sansing, Lauren H.; email: lauren.sansing@yale.edu; Mullen, Michael T.; email: Michael.Mullen@uphs.upenn.edu; Murthy, Santosh B.; email: sam9200@med.cornell.edu; Mould, Andrew; email: amould@jhmi.edu; Nekoovaght-Tak, Saman; email: snekoov1@gmail.com; Hanley, Daniel F.; email: dhanley@jhmi.edu (MDPI, 2021-07-30)
      We investigated cerebrospinal fluid (CSF) expression of inflammatory cytokines and their relationship with spontaneous intracerebral and intraventricular hemorrhage (ICH, IVH) and perihematomal edema (PHE) volumes in patients with acute IVH. Twenty-eight adults with IVH requiring external ventricular drainage for obstructive hydrocephalus had cerebrospinal fluid (CSF) collected for up to 10 days and had levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNFα), and C-C motif chemokine ligand CCL2 measured using enzyme-linked immunosorbent assay. Median [IQR] ICH and IVH volumes at baseline (T0) were 19.8 [5.8–48.8] and 14.3 [5.3–38] mL respectively. Mean levels of IL-1β, IL-6, IL-10, TNF-α, and CCL2 peaked early compared to day 9–10 (p 0.05) and decreased across subsequent time periods. Levels of IL-1β, IL-6, IL-8, IL-10, and CCL2 had positive correlations with IVH volume at days 3–8 whereas positive correlations with ICH volume occurred earlier at day 1–2. Significant correlations were found with PHE volume for IL-6, IL-10 and CCL2 at day 1–2 and with relative PHE at days 7–8 or 9–10 for IL-1β, IL-6, IL-8, and IL-10. Time trends of CSF cytokines support experimental data suggesting association of cerebral inflammatory responses with ICH/IVH severity. Pro-inflammatory markers are potential targets for injury reduction.
    • Early results using N-terminal pro-B-Type Natriuretic Peptide (pro-BNP) as a biomarker for the efficacy of secondary extension technique (SET) in improving myocardial function in dialysis patients with high flow fistulas.

      Haque, Mr Adam; email: adam.haque@manchester.ac.uk; Al-Khaffaf, Mr Haytham (2021-11-04)
      The association of dialysis fistulas and heart failure is believed to be due to high cardiac output. N-terminal pro-B-Type Natriuretic Peptide (pro-BNP) which is secreted by the cardiac ventricles in response to excessive stretching of the myocytes has been used as a marker of heart failure with 90% sensitivity. We report our early experience using pro-BNP levels to test the efficacy of the novel 'secondary extension technique' (SET) in improving myocardial function by reducing fistula flow. 11 patients with high fistula flows (>3000ml/m, all brachio-cephalic) and raised pro-BNP underwent SET between 2011 and 2015. SET involves extending the anastomosis from brachial to either proximal radial or ulnar arteries. We measured pro-BNP levels, fistula flow and clinical improvements both pre and post operatively. SET resulted in a median (IQR) flow rate decrease of 57.9 (11.9) % which correlated with a fall in pro-BNP of 69.6 (39) %. 7 of the 11 patients in the series pro-BNP level returned to a normal value at average follow-up of 3 months post SET. All patients had HOF-related symptom resolution post-procedure and remained asymptomatic at last follow-up CONCLUSION: Our pilot data suggests that SET is an effective way of reducing fistula flow. It also shows that BNP may be a reliable biomarker in assessing the impact of the technique on cardiac function. These results warrant further investigation in the form of a definitive, multicentre study. [Abstract copyright: Copyright © 2021. Published by Elsevier Inc.]
    • Eating for 1, Healthy and Active for 2; feasibility of delivering novel, compact training for midwives to build knowledge and confidence in giving nutrition, physical activity and weight management advice during pregnancy

      Basu, Andrea J.; Kennedy, Lynne; Tocque, Karen; Jones, Sharn; University of Chester; Wrexham Maelor Hospital (BioMed Central, 2014-07-04)
      Background: Women in Wales are more likely to be obese in pregnancy than in any other United Kingdom (UK) country. Midwives are ideally placed to explore nutrition, physical activity and weight management concerns however qualitative studies indicate they lack confidence in raising the sensitive issue of weight. Acknowledging this and the reality of finite time and resources, this study aimed to deliver compact training on nutrition, physical activity and weight management during pregnancy to increase the knowledge and confidence of midwives in this subject. Methods A compact training package for midwives was developed comprising of evidence based nutrition, physical activity and weight management guidance for pregnancy. Training was promoted via midwifery leads and delivered within the Health Board. Questionnaires based on statements from national public health guidance were used to assess changes in self-reported knowledge and confidence pre and post training. Descriptive statistics were applied and 95% confidence intervals were calculated. Results 43 midwives registered for training, 32 (74%) attended and completed the questionnaires. Although, pre training knowledge and confidence varied between participants, statistically significant improvements in self-reported knowledge and confidence were observed post training. 97% indicated knowledge of pregnancy specific food and nutrition messages as ‘better’ (95% CI 85 to 100), as opposed to 3% stating ‘stayed the same’ – 60% stated ‘much better’. 83% indicated confidence to explain the risks of raised BMI in pregnancy was either ‘much’ or ‘somewhat better’ (95% CI 66 to 93), as opposed to 17% stating ‘stayed the same’. 89% indicated confidence to discuss eating habits and physical activity was ‘much’ or ‘somewhat better’ (95% CI 73 to 97) as opposed to 11% stating ‘stayed the same’. Emergent themes highlighted that training was positively received and relevant to midwifery practice. Conclusions This study provides early indications that a compact nutrition, physical activity and weight management training package improves midwives self-reported knowledge and confidence. Cascading training across the midwifery service in the Health Board and conducting further studies to elicit longer term impact on midwifery practice and patient outcomes are recommended.
    • Editorial for the Special Issue on “Emerging Trends in Phononic Crystals”

      Nouh, Mostafa; orcid: 0000-0002-2135-5391; email: mnouh@buffalo.edu; Parnell, William J.; email: william.parnell@manchester.ac.uk; Hussein, Mahmoud I.; email: mih@colorado.edu (MDPI, 2021-08-03)
      Over the past three decades, the study of phononic crystals (PCs) has rapidly evolved into a prominent research field offering a versatile platform for the creation of structured materials with salient properties [...]
    • Editorial: Cooperation and Coordination in the Family

      Savage, James L.; email: james.savage@cantab.net; Hinde, Camilla A.; Johnstone, Rufus A. (Frontiers Media S.A., 2020-12-07)
    • Editorial: Coronavirus Disease (COVID-19): The Mental Health, Resilience, and Communication Resources for the Short- and Long-term Challenges Faced by Healthcare Workers

      Mitchell, Andrew E. P.; email: a.mitchell@chester.ac.uk; Galli, Federica; Keyworth, Chris; Vegni, Elena; Salas, Eduardo (Frontiers Media S.A., 2022-04-18)
    • Editorial: New Drug Targets for Proteotoxicity in Cardiometabolic Diseases

      Ren, Jun; email: jren@uw.edu; Wang, Xin; email: xin.wang@manchester.ac.uk; Zhang, Yingmei; email: zhangym197951@126.com (Frontiers Media S.A., 2021-09-16)
    • Educational experiences of pupils with Down syndrome in the UK.

      Hargreaves, Stephanie; Holton, Sarah; Baxter, Rebecca; Burgoyne, Kelly; email: kelly.burgoyne@manchester.ac.uk (2021-10-29)
      Though research has identified that increasing numbers of pupils with Down syndrome (DS) in the UK are educated in mainstream schools, little detailed information about the educational experiences of pupils with DS is available. This study explored parent views of the educational experiences of pupils with DS attending UK schools (Reception-Year 11) using an online survey. Responses from 569 parents were collected. Overall, 65 % of pupils were in mainstream schools but this was more common at primary (80 %) than secondary school (37 %). Pupils participated in most academic and social activities alongside their peers but were commonly not accessing all opportunities. Many pupils received additional support in school including external professional services. Frequent meetings between parents and teachers/teaching assistants indicated high levels of collaboration. Teachers and teaching assistants were largely viewed as responsible for children's learning. Overall, respondents reported satisfaction with provision. Many pupils with DS in the UK are able to access a broad and balanced curriculum but this is not the case for all. Ways in which provision can be enhanced are discussed. [Abstract copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.]
    • Educational support needs of injured children and their families after a child's traumatic injury: A qualitative study.

      Jones, Samantha; email: samantha.jones-3@manchester.ac.uk; Tyson, Sarah; Davis, Naomi; Yorke, Janelle (2021-11-03)
      To explore the educational support needs of injured children and families. Thirteen injured children and/or their parents (n = 19) discharged from a major trauma centre within 12 months. Semi-structured interviews analysed with thematic analysis. Theme 1: communication and information needs. Schools need help to understand the effects of children's injuries and the adjustments required for their return to school, such as how to involve the children in the more active elements of the curriculum. Thus, effective communication between the injured child, their family, health and education professionals and outside agencies is needed. A specialist key-worker could co-ordinate communication and school return. Theme 2: Educational support needs. Injured children experience changes to their appearance, new symptoms, and altered physical and cognitive abilities. Their absence from school often adversely affects their friendships. Consequently, injured children need continued access to education throughout recovery, support with learning, a flexible timetable, opportunities for social integration, involvement in all aspects of the curriculum, and environmental adaptations to maintain their health and safety. Children with different types of injuries have similar needs for flexible learning and environmental accommodations. Social integration and participation in physical activity should be specific goals for school return.
    • Educators’ experiences and perspectives of child weight discussions with parents in primary school settings

      Coupe, Nia; orcid: 0000-0003-4974-5794; Peters, Sarah; Ayres, Matilda; Clabon, Katie; Reilly, Alexandra; Chisholm, Anna; email: anna.chisholm@liverpool.ac.uk (BioMed Central, 2022-04-22)
      Abstract: Background: The role of schools in addressing rising childhood obesity levels has been acknowledged, and numerous diet- and physical activity-related interventions exist. Aside from formal interventions, opportunistic parent-educator conversations about child weight can arise, particularly in primary school settings, yet little is known about how useful these are. This study aimed to understand the utility of child weight related conversations with parents through exploring educators’ experiences and perspectives. Methods: This qualitative study consisted of semi-structured interviews conducted with primary school teaching staff in the United Kingdom (N = 23), recruited through purposive and subsequent snowball sampling. Interviews were audio-recorded, transcribed, and analysed using thematic analysis. Results: Participants identified opportunities and need for child weight discussions in schools. However, conversations were prevented by the indirect and sensitive nature of conversations, and educators’ professional identity beliefs. Using pre-existing face-to-face opportunities, good parent-teacher relationships and holistic approaches to child health and wellbeing were reported as important in optimising these conversations. Conclusions: Whilst educator-parent child weight discussions are necessary, discussions are highly challenging, with contradictory views on responsibility sometimes resulting in avoidance. Educators’ roles should be clarified, and communication training tailored to increase teacher confidence and skills. Current social distancing will likely reduce opportunistic encounters, highlighting a need to further improve communication routes.
    • Effect of breakfast cereal type on portion size and nutritional implications.

      Lewis, Isabelle M; Boote, Lucy; Butler, Tom; orcid: 0000-0003-0818-1566 (2021-02-17)
      The present study aimed to assess the effect of different types of breakfast cereal on portion size and the nutritional implications of potential under or overserving. A cross-sectional analysis was performed using one BC from the 7 established BC manufacturing methods (flaking [F], gun puffed [GP], oven puffed [OP], extruded gun puffed [EGP], shredded wholegrain [SW], biscuit formed [BF], and granola). Participants were asked to pour cereal as if they were serving themselves (freepour). Difference between the freepour and recommended serving size (RSS) were calculated (DFR). The Friedman test followed by Dunn's multiple comparison test was used to test for a significant differences between cereal categories. City of Chester, North West of the UK. Adults (n=169; n=110 female, 32±18 years). Freepour values were greater than RSS for all categories of BC. Median values for denser cereals such as SW, granola and oats were significantly (P<0.001) greater than all other categories with granola having the highest median freepour value of 95 g. Median (and range of) DFR weight values for granola were significantly higher than other BCs (50.0 g [-24.0-267.0g], P<0.001). BCs with the lowest median DFRs were F1 (7.0 g [-20-63.0g]), GP (6.0 g [-26.0-69.0g]), EGP (6.0 g [-26.0-56.0g]), OP (5.0 g [-27.0-53.0g]), and BF (0.0 g [-28.2-56.4g]). The degree of overserving may be related to the type of BC with denser cereals more readily overserved. Encouraging manufacturers to reformulate cereals and improving their nutritional properties may have benefit in reducing excess energy intake.
    • Effect of centrally and peripherally acting GABA

      Badri, Huda; email: huda.badri@manchester.ac.uk; LGibbard, Carmen; Denton, Dimitra; Satia, Imran; Dockry, Rachel J; Holt, Kimberley; Escott, Jane; Wilkinson, Greame; Holt, Alison; Canning, Brendan J; et al. (2021-09-24)
      Currently there are no effective licensed anti-tussive therapies. Understanding how the neuronal mechanisms mediating the cough reflex in animal models translate to humans is important for the development of effective therapies. Pre-clinical studies suggest that the activation of GABA receptors in both the peripheral and central nervous systems inhibit cough. To compare the effect of central and peripherally acting GABA agonists (lesogaberan and baclofen) on the cough reflex in healthy volunteers. We performed a single center, double-blind, double-dummy, three-way crossover trial in healthy controls comparing single doses of lesogaberan (120mg MR), with baclofen (40mg) and placebos. Cough responses to inhaled capsaicin were assessed at screening and 2h post-dose on each study day. The primary endpoint was the maximum number of coughs evoked at any concentration of capsaicin (Emax) and the secondary endpoint was the concentration evoking 50% of the maximal response (ED50). Fifteen participants enrolled onto the study (median age 29 (IQR 25-44) years; 7 females, mean BMI 24.6(±3.0). Lesogaberan treatment produced a small, statistically significant increase in Emax compared with placebo [mean 13.4coughs (95%CI 10.1-17.9) vs. 11.8coughs (8.8-15.9), p=0.04], but had no effect on ED50 [geometric mean 47.4μM (95%CI 24.4-91.7) vs 37.6 μM (95%CI 19.2-73.5), p=0.37]. In contrast, baclofen had no significant effect on Emax (11.1, 95%CI 8.1-15.4) (p=0.23), but significantly increased ED50 compared with placebo (geometric mean 75.2μM (95%CI 37.2-151.8), p=0.002). This data suggests the anti-tussive actions of GABA agonists, in healthy volunteers, occur in the central rather than the peripheral nervous system. [Abstract copyright: Copyright © 2021. Published by Elsevier Ltd.]
    • Effect of combined home-based, overground robotic-assisted gait training and usual physiotherapy on clinical functional outcomes in people with chronic stroke: A randomized controlled trial

      Wright, Amy; orcid: 0000-0002-7006-6465; Stone, Keeron; Martinelli, Louis; Fryer, Simon; Smith, Grace; Lambrick, Danielle; Stoner, Lee; orcid: 0000-0002-0682-2270; Jobson, Simon; Faulkner, James; orcid: 0000-0002-3704-6737 (SAGE Publications, 2020-12-27)
      Objectives: To assess the effect of a home-based over-ground robotic-assisted gait training program using the AlterG Bionic Leg orthosis on clinical functional outcomes in people with chronic stroke. Design: Randomized controlled trial. Setting: Home. Participants: Thirty-four ambulatory chronic stroke patients who recieve usual physiotherapy. Intervention: Usual physiotherapy plus either (1)10-week over-ground robotic-assisted gait training program ( n = 16), using the device for ⩾30 minutes per day, or (2) control group ( n = 18), 30 minutes of physical activity per day. Measurements: The primary outcome was the Six-Minute Walk Test. Secondary outcomes included: Timed-Up-and-Go, Functional Ambulation Categories, Dynamic Gait Index and Berg Balance Scale. Physical activity and sedentary time were assessed using accelerometry. All measurements were completed at baseline, 10 and 22 weeks after baseline. Results: Significant increases in walking distance were observed for the Six-Minute Walk Test between baseline and 10 weeks for over-ground robotic-assisted gait training (135 ± 81 m vs 158 ± 93 m, respectively; P ⩽ 0.001) but not for control (122 ± 92 m vs 119 ± 84 m, respectively). Findings were similar for Functional Ambulation Categories, Dynamic Gait Index and Berg Balance Scale (all P ⩽ 0.01). For over-ground robotic-assisted gait training, there were increases in time spent stepping, number of steps taken, number of sit-to-stand transitions, and reductions in time spent sitting/supine between baseline and 10 weeks (all P &lt; 0.05). The differences observed in all of the aforementioned outcome measures were maintained at 22 weeks, 12 weeks after completing the intervention (all P &gt; 0.05). Conclusion: Over-ground robotic-assisted gait training combined with physiotherapy in chronic stroke patients led to significant improvements in clinical functional outcomes and physical activity compared to the control group. Improvements were maintained at 22 weeks.
    • Effect of Different Root Canal Irrigant Solutions on the Release of Dentin-Growth Factors: A Systematic Review and Meta-Analysis

      Tavares, Sandro; orcid: 0000-0003-4890-4220; email: sandro.tavares04@gmail.com; Pintor, Andrea; email: andrea_pintor@hotmail.com; Mourão, Carlos Fernando de Almeida Barros; orcid: 0000-0001-5775-0222; email: mouraocf@gmail.com; Magno, Marcela; email: marcela.magno@hotmail.com; Montemezzi, Pietro; email: m.montemezzi@libero.it; Sacco, Roberto; email: roberto.sacco@manchester.ac.uk; Alves, Gutemberg; orcid: 0000-0003-0016-4809; email: gutopepe@yahoo.com.br; Scelza, Miriam Zaccaro; orcid: 0000-0002-2132-4755; email: scelza@terra.com.br (MDPI, 2021-10-05)
      Irrigant solutions are used to promote dentin-growth factors (GF) release for regenerative endodontics. This review aimed to evaluate the reports comparing the release of GFs using different root canal irrigant solutions. Eligible studies compared the in vitro GF release in human teeth after the use of at least two distinct solutions. A search was conducted on Pubmed, Scopus, Web of Science, and Lilacs on 11 August 2021. Risk of bias was assessed using SciRAP. Study characteristics and quantitative data were extracted, and meta-analyses were performed for the mean difference (95% confidence interval) of the release of transforming growth factors Beta 1 (TGF-β1) by EDTA compared to other irrigants. Of sixteen eligible studies, eight were included in quantitative analysis. ELISA assays showed higher TGF-β1 release from 10% EDTA compared to 10% citric acid (p 0.00001). Immunogold assays showed higher levels of TGF-β1 for 17% EDTA (p 0.00001) compared to 10% citric acid. GRADE identified a low to very low certainty of evidence. These results point to an increased release of TGF-β1 in dentin treated with EDTA. The high heterogeneity and very low certainty of the evidence demand further studies before EDTA indication as a better irrigant for regenerative endodontics. Registration: CRD42020160871 (PROSPERO).
    • Effect of layered water structures on the anomalous transport through nanoscale graphene channels

      Chen, S; orcid: 0000-0002-8118-5849; Draude, A P; Nie, A X C; Fang, H P; Walet, N R; orcid: 0000-0002-2061-5534; Gao, Shiwu; email: swgao@csrc.ac.cn; Li, J C; email: j.c.li@manchester.ac.uk (IOP Publishing, 2018-08-16)
      Abstract: We analyse the enhanced flow rate of water through nano-fabricated graphene channels that has been recently observed experimentally. Using molecular dynamics simulations in channels of similar lateral dimensions as the experimental ones, our results reveal for the first time a relationship between water structure and the variation of flux in the rectangular graphene channels. The substantial enhancement in the flow rate compared to Poieseuille flow is due to the formation of layered 2D structures in the confined space, which persists up to a channel height of 2.38 nm, corresponding to six graphene layers. The structure of the water shows an intricate crystal of pentagonal and square tiles, which has not been observed before. Beyond six layers we find a sudden drop in flux due to the disordering of the water, which can be understood by classical flow dynamics.
    • Effect of layered water structures on the anomalous transport through nanoscale graphene channels

      Chen, S; orcid: 0000-0002-8118-5849; Draude, A P; Nie, A X C; Fang, H P; Walet, N R; orcid: 0000-0002-2061-5534; Gao, Shiwu; email: swgao@csrc.ac.cn; Li, J C; email: j.c.li@manchester.ac.uk (IOP Publishing, 2018-08-16)
      Abstract: We analyse the enhanced flow rate of water through nano-fabricated graphene channels that has been recently observed experimentally. Using molecular dynamics simulations in channels of similar lateral dimensions as the experimental ones, our results reveal for the first time a relationship between water structure and the variation of flux in the rectangular graphene channels. The substantial enhancement in the flow rate compared to Poieseuille flow is due to the formation of layered 2D structures in the confined space, which persists up to a channel height of 2.38 nm, corresponding to six graphene layers. The structure of the water shows an intricate crystal of pentagonal and square tiles, which has not been observed before. Beyond six layers we find a sudden drop in flux due to the disordering of the water, which can be understood by classical flow dynamics.
    • Effect of Micro Solidification Crack on Mechanical Performance of Remote Laser Welded AA6063 Fillet Lap Joint in Automotive Battery Tray Construction

      Sun, Tianzhu; email: Tianzhu.sun@warwick.ac.uk; Franciosa, Pasquale; email: P.Franciosa@warwick.ac.uk; Liu, Conghui; email: Conghui.liu@postgrad.manchester.ac.uk; Pierro, Fabio; email: fabiopierro91@gmail.com; Ceglarek, Darek; email: D.J.Ceglarek@warwick.ac.uk (MDPI, 2021-05-15)
      Remote laser welding (RLW) has shown a number of benefits of joining 6xxx aluminium alloys such as high processing speed and process flexibility. However, the crack susceptibility of 6xxx aluminium alloys during RLW process is still an open problem. This paper experimentally assesses the impact of transverse micro cracks on joint strength and fatigue durability in remote laser welding of AA6063-T6 fillet lap joints. Distribution and morphology of transverse micro cracks were acquired by scanning electron microscope (SEM) on cross-sections. Grain morphology in the weld zone was determined by electron backscatter diffraction (EBSD) while static tensile and dynamic fatigue tests were carried out to evaluate weld mechanical performance. Results revealed that increasing welding speed from 2 m/min to 6 m/min did not introduce additional transverse micro cracks. Additionally, welding at 2 m/min resulted in tensile strength improvement by 30% compared to 6 m/min due to the expansion of fusion zone, measured by the throat thickness, and refinement of columnar grains near fusion lines. Furthermore, the weld fatigue durability is significantly higher when fracture occurs in weld root instead of fusion zone. This can be achieved by increasing weld root angle with optimum weld fatigue durability at around 55°.
    • Effect of Moderate and Severe Hemophilia a on Daily Life in Children and Their Caregivers: A CHESS Paediatrics Study Analysis

      Khair, Kate; Nissen, Francis; Silkey, Mariabeth; Burke, Tom; Shang, Aijing; Aizenas, Martynas; Meier, Oliver; O'Hara, Jamie; Noone, Declan (Elsevier, 2021-08-03)
      Introduction: Hemophilia A (HA) is a congenital bleeding disorder, caused by a deficiency in clotting factor VIII (FVIII) and characterized by uncontrolled bleeding and progressive joint damage. This analysis assesses the impact of disease burden on the daily life of children with hemophilia A (CwHA) and their caregivers, addressing a deficit of current research on this topic. Methods: The Cost of Haemophilia in Europe: a Socioeconomic Survey in a Paediatric Population (CHESS Paediatrics) is a retrospective, burden-of-illness study in children with moderate and severe HA (defined by endogenous FVIII [IU/dL] relative to normal; moderate, 1-5%; severe, <1%) across France, Germany, Italy, Spain and the UK. CwHA were recruited and stratified by both age group (0-5 years:6-11 years:12-17 years=1:1:1) and disease severity (severe:moderate=approximately 2:1, prioritizing children with severe HA [CwSHA]). Data for this analysis were captured from physicians, children, and their caregivers. Physicians completed online case report forms for treated children, and the child and/or their caregivers completed a paper-based questionnaire utilizing 5-point Likert scales. For CwHA aged 0-7, the questionnaire was completed by the caregiver, while for CwHA aged 8-17, children and caregivers completed different sections. Hours of care provided by the caregiver and work lost by the caregiver were reported as median values due to non-normal data distribution. Informed consent was obtained for all participants. Upon review, the study was approved by the University of Chester ethical committee. Results: Data from child/caregiver questionnaires were available for 196 CwHA (moderate, 25.5%; severe, 74.5%); the majority of these children, as expected, were receiving prophylaxis (72.4%), and did not have FVIII inhibitors (89.8%; Table 1). There was a direct impact of disease burden on CwHA, particularly with regard to physical and social activities (Figure 1). Overall, it was agreed or strongly agreed by the child or caregiver that 48.0% and 57.5% of children with moderate HA (CwMHA) and CwSHA respectively, have reduced physical activity due to HA, and 46.0% and 57.5%, respectively, have reduced social activity due to HA. A total of 36.0% and 61.0% of CwMHA and CwSHA, respectively, had adapted their treatment in anticipation of physical or social activity (Table 1). Furthermore, 34.0% of CwMHA and 55.4% of CwSHA were frustrated due to their disease, and many (CwMHA, 36.0%; CwSHA, 50.7%) felt that they had missed opportunities (Figure 1). For 66.0% of CwMHA and 76.0% of CwSHA, it was reported that their daily life was compromised due to their HA. Caregivers provided a median (interquartile range [IQR]) of 19.0 (10.0-59.5) and 12.0 (5.0-20.0) hours a week of care for the hemophilia-related needs of their CwMHA (n=30) or CwSHA (n=105), respectively. Of those who responded, 17.4% (n=4/23) and 25.0% (n=20/80) of caregivers to CwMHA or CwSHA, respectively, stated they have lost work due to their caregiving duty. This was more than twice as common for caregivers in families with multiple CwHA (42.9%, n=9/21 responses) compared with those in families with one CwHA (18.5%, n=15/81 responses). Median (IQR) hours of work per week estimated to be lost were 20.0 (17.0-22.0) for caregivers of CwMHA (n=4) and 12.5 (4.50-20.0) for caregivers of CwSHA (n=20). Conclusions: In conclusion, both children and caregivers make sacrifices in their daily lives due to HA; many CwHA reported reduced physical and social activities, fewer opportunities and feelings of frustration due to their HA. Caregivers reported spending a significant number of hours caring for their child and some reported losing work due to their caring responsibilities. However, some outcomes may be limited by the small number of respondents and narrow response options, particularly those regarding the caregiver burden. Responses on the hours of work lost may be subject to selection bias, as caregivers who have lost work may be more likely to respond to this question. Additionally, as this question is targeted at caregivers in employment, it is unknown if some caregivers have left employment due to their caregiving responsibilities. According to this analysis, children/caregivers are frequently required to adapt the child's treatment before the child engages in activities. Overall, the burden of disease was similar in children with moderate and severe HA. Disclosures Khair: Takeda: Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Biomarin: Consultancy; HCD Economics: Consultancy; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medikhair: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Haemnet: Membership on an entity's Board of Directors or advisory committees. Nissen: GSK: Research Funding; Novartis: Research Funding; Actelion: Consultancy; F. Hoffmann-La Roche Ltd: Current Employment. Silkey: Aerotek AG: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Burke: HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Shang: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Aizenas: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Meier: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. O'Hara: HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy. Noone: Research Investigator PROBE: Research Funding; Healthcare Decision Consultants: Membership on an entity's Board of Directors or advisory committees; European Haemophilia Consortium: Membership on an entity's Board of Directors or advisory committees.