Effects of the ActiveHip+ mHealth intervention on the recovery of older adults with hip fracture and their family caregivers:a multicentre open-label randomised controlled trial

Background: Mobile health (mHealth) systems are a promising alternative for rehabilitation of hip fracture, addressing constrained healthcare resources. Half of older adults fails to recover their pre-fracture routines, which imposes a burden on caregivers. We aimed to test the effectiveness of the 3-month ActiveHip + mHealth intervention on physical and psychological outcomes of older adults with hip fracture and their family caregivers. Methods: In a multicentre open-label randomised controlled trial conducted across 3 hospitals in Andalusia (Spain), patients older than 65 with a hip fracture, who were previously independent and lacked cognitive impairment were recruited alongside with their caregivers. Participants were randomly allocated (1:1) to the intervention group (ActiveHip+) or control (usual care) group. The intervention group underwent a 12-week health education and tele-rehabilitation programme through the ActiveHip + mHealth intervention. The primary outcome, physical performance, was assessed using the Short Physical Performance Battery at three time points: at hospital discharge (baseline), 3-month after surgery (post intervention) and 1-year after surgery follow-up. Primary analyses of primary outcomes and safety data followed an intention-to-treat approach. This study is registered at ClinicalTrials.gov, NCT04859309. Findings: Between June 1st, 2021 and June 30th, 2022 data from 105 patients and their caregivers were analysed. Patients engaged in the ActiveHip + mHealth intervention (mean 7.11 points, SE 0.33) showed higher physical performance compared with patients allocated in the control group (mean 5.71 points, SE 0.32) at 3 months after surgery (mean difference in change from baseline 1.40 points, SE 0.36; puncorrected = 0.00011). These benefits were not maintained at 1-year after surgery follow-up (mean difference in change from baseline 0.19 points, SE 0.47; puncorrected = 0.68). No adverse events, including falls and refractures, were reported during the tele-rehabilitation sessions. At 3-months, the intervention group had 2 falls, compared to 4 in the control group, with no observed refractures. At the 1-year follow-up, the intervention group experienced 7 falls and 1 refracture, while the control group had 13 falls and 2 refractures. Interpretation: This study suggests that the ActiveHip + mHealth intervention may be effective for recovering physical performance in older adults with hip fracture. Importantly, the implementation of ActiveHip + into daily clinical practice may be feasible and has already been adopted in 18 hospitals, mostly in Spain but also in Belgium and Portugal. Thus, ActiveHip + could offer a promising solution when rehabilitation resources are limited. However, its dependence on caregiver support and the exclusion of participants with cognitive impairment makes it necessary to be cautious about its applicability. In addition, the non-maintenance of the effectiveness at 1-year follow-up highlights the need of refinement the ActiveHip + intervention to promote long-lasting behavioural changes. Funding: EIT Health and the Ramón y Cajal 2021 Excellence Research Grant action from the Spanish Ministry of Science and Innovation.</p

Coronary Artery Disease and Prognosis of Heart Failure with Reduced Ejection Fraction.

Our aim was to determine the prognostic impact of coronary artery disease (CAD) on heart failure with reduced ejection fraction (HFrEF) mortality and readmissions. From a prospective multicenter registry that included 1831 patients hospitalized due to heart failure, 583 had a left ventricular ejection fraction of <40%. In total, 266 patients (45.6%) had coronary artery disease as main etiology and 137 (23.5%) had idiopathic dilated cardiomyopathy (DCM), and they are the focus of this study. Significant differences were found in Charlson index (CAD 4.4 ± 2.8, idiopathic DCM 2.9 ± 2.4, p < 0.001), and in the number of previous hospitalizations (1.1 ± 1, 0.8 ± 1.2, respectively, p = 0.015). One-year mortality was similar in the two groups: idiopathic DCM (hazard ratio [HR] = 1), CAD (HR 1.50; 95% CI 0.83-2.70, p = 0.182). Mortality/readmissions were also comparable: CAD (HR 0.96; 95% CI 0.64-1.41, p = 0.81). Patients with idiopathic DCM had a higher probability of receiving a heart transplant than those with CAD (HR 4.6; 95% CI 1.4-13.4, p = 0.012). The prognosis of HFrEF is similar in patients with CAD etiology and in those with idiopathic DCM. Patients with idiopathic DCM were more prone to receive heart transplant.This research was funded by CIBERCV I and supported by the Instituto de Salud Carlos III. L.V. is funded by the Instituto de Salud Carlos III, Spain (CM20/00104 and ).S

EMBR-25. Genome-wide genetic and epigenetic assessment of group 4 Medulloblastoma for improved, biomarker driven, prognostication and risk-stratification

Introduction: Medulloblastoma (MB) is the most common malignant brain tumour in children. The most frequent molecular subgroup, Group 4 (MBGrp4) accounts for ~35/40% of cases, however it has the least understood underlying biology. Clinical outcomes are heterogeneous in MBGrp4 and are not accounted for by established clinico-pathological risk factors. There is now a requirement for a comprehensive study of MBGrp4, considering established clinico-pathological features and novel molecular biomarkers to enhance risk-stratification and identify novel therapeutic targets. Methods: A clinically-annotated, retrospective MBGrp4 discovery cohort (n = 420) was generated from UK CCLG institutions, collaborating European centres and SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 clinical trials. Contemporary, multi-omics profiling was performed. Focal and arm level copy number aberrations (CNAs) were determined from molecular inversion probe (MIP) or DNA methylation array which additionally provided next generation non-WNT/non-SHH (Grp3/Grp4) subtype classifications. Targeted next-generation DNA sequencing was performed to overlay the mutational landscape. Survival modelling was carried out with patients &gt;3 years old who received craniospinal irradiation. Results: MBGrp4 subtypes were assigned to 88% of tumours with available data. Subtype VIII was strongly associated with i17q (p&lt;0.0001). The favourable-risk cytogenetic signature (2 or 3 of; chromosome 7 gain, chromosome 8 loss and/or chromosome 11 loss) associated with both subtypes VI and VII (p&lt;0.0001). MYCN amplifications were strongly associated with subtype V (p&lt;0.0001) in addition to 16q loss (p&lt;0.0001). The high-risk CNA group was enriched for mutations in genes involved in chromatin remodelling (p&lt;0.0001). Risk factors were identified from multivariate survival modelling. Subtype and CNA groups contributed to improved risk-stratification models that outperformed current clinical schemes. Conclusion: Comprehensive genetic and epigenetic profiling in this large retrospective cohort has improved our understanding of the molecular and clinical heterogeneity within MBGrp4. Incorporation of molecular biomarkers improved risk-stratification for MBGrp4

Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas

© The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies.info:eu-repo/semantics/publishedVersio

A pan-European epidemiological study reveals honey bee colony survival depends on beekeeper education and disease control

Reports of honey bee population decline has spurred many national efforts to understand the extent of the problem and to identify causative or associated factors. However, our collective understanding of the factors has been hampered by a lack of joined up trans-national effort. Moreover, the impacts of beekeeper knowledge and beekeeping management practices have often been overlooked, despite honey bees being a managed pollinator. Here, we established a standardised active monitoring network for 5 798 apiaries over two consecutive years to quantify honey bee colony mortality across 17 European countries. Our data demonstrate that overwinter losses ranged between 2% and 32%, and that high summer losses were likely to follow high winter losses. Multivariate Poisson regression models revealed that hobbyist beekeepers with small apiaries and little experience in beekeeping had double the winter mortality rate when compared to professional beekeepers. Furthermore, honey bees kept by professional beekeepers never showed signs of disease, unlike apiaries from hobbyist beekeepers that had symptoms of bacterial infection and heavy Varroa infestation. Our data highlight beekeeper background and apicultural practices as major drivers of honey bee colony losses. The benefits of conducting trans-national monitoring schemes and improving beekeeper training are discussed

MEDB-71. Molecular characterisation of group 4 medulloblastoma improves risk-stratification and its biological understanding

Group 4 (MBGrp4) accounts for ~40% of medulloblastoma and the majority of non-WNT/non-SHH cases, yet its underpinning biology is poorly understood, and survival outcomes are not sufficiently explained by established clinico-pathological risk factors. We investigated the clinical and molecular correlates of MBGrp4, including second-generation methylation non-WNT/non-SHH subtypes (I-VIII) and whole chromosome aberration (WCA) subtypes (defined by chromosome 7 gain, 8 loss, and 11 loss; WCA-favourable risk [WCA-FR] ≥2 features, WCA-high risk [WCA-HR] ≤1 feature). A clinically-annotated MBGrp4 discovery cohort (n=378) was assembled from UK CCLG institutions, collaborating centres and SIOP-UKCCSG-PNET3/HIT-SIOP-PNET4 clinical trials. Contemporary molecular profiling integrating methylation/WCA subtypes and next-generation sequencing was performed. Survival modelling was carried out with patients &gt;3 years old who received craniospinal irradiation (n=336). Association analysis confirmed relationships between methylation and WCA subtypes. Subtypes VI and VII were enriched for WCA-FR (p&lt;0.0001) and aneuploidy, whereas subtype VIII was defined solely by i17q (p&lt;0.0001). Whilst we observed an overall low mutational burden, WCA-HR harboured recurrent mutations in genes involved in chromatin remodelling (p=0.007). No gene-specific events were associated with disease risk, however integration of both methylation subtype and WCA groups enabled improved risk-stratification survival models that outperformed current schemes. The optimal MBGrp4-specific model stratified patients into: favourable-risk (local disease, subtype VII or subtype VI with WCA-FR; 39/194 [20%], 97% 5-year PFS), very-high-risk (metastatic disease with WCA-HR; 71/194 [37%], 50% 5-year PFS) and high-risk (remaining patients; 84/194 [43%], 67% 5-year PFS). Findings were validated in independent cohorts. Comprehensive clinico-molecular assessment of MBGrp4 provides important understanding of its clinical and biological heterogeneity. Our novel MBGrp4 stratification scheme removes standard risk disease and identifies a favourable risk group (20% of MBGrp4) with potential for therapy de-escalation. Current therapeutic strategies are insufficient for the very-high risk group (encompassing 37% of MBGrp4), for whom novel therapies are urgently required