Theory of change and strategic priorities of the world federation of haemophilia.

The World Federation of Haemophilia (WFH) is a global network of national member organizations (NMOs) that advocate, collectively and individually, to improve lives of people with inherited bleeding disorders. The WFH vision of "Treatment for All" speaks to a future in which all people with an inherited bleeding disorder will have access to care, regardless of their gender or where they live. Over the last several years, initiatives including the WFH Humanitarian Aid program, the World Bleeding Disorders Registry, and Guidelines for the Management of Haemophilia and von Willebrand disease have significantly changed how the WFH and its partners work to improve and sustain care for people with bleeding disorders. Following an extensive consultation that included over 200 stakeholders from 70 countries, a Theory of Change was developed, and strategic priorities identified, to clearly define the WFH's intended impact and point of accountability to its stakeholders, and to determine how and through who those goals will be achieved. Both should help the WFH better support its NMOs and healthcare providers around the world in their efforts to improve access to diagnosis and care, as new therapies revolutionize the treatment landscape and the fallout of the global pandemic continues to challenge the ways in which we work and connect. Global collaboration of all stakeholders, based on their resources, objectives and skills, will be required to achieve these goals and to ensure more people have reliable access to safe treatment and care, regardless of their bleeding disorder, gender, or where they live.

Bridging the gap: Survey highlights challenges and solutions in outreach and identification of people with inherited bleeding disorders.

INTRODUCTION: Inherited bleeding disorders (IBD) are genetic conditions that affect blood clotting, leading to complications such as prolonged or spontaneous bleeding into muscles or joints. Early identification and treatment are crucial to prevent complications and improve outcomes. However, effective patient outreach and identification programs for IBD face significant challenges globally. AIM: This study aimed to identify successful patient outreach initiatives for IBD, barriers encountered during implementation, and approaches used to overcome them. METHODS: The World Federation of Haemophilia (WFH) conducted a survey of its national member organizations and other patient associations, totalling 153 organizations, to identify common strategies, barriers to their implementation, and solutions for outreach and the identification of people with IBD. The survey consisted of both closed-ended and open-ended questions, and the data were analysed using descriptive statistics and thematic analysis. RESULTS: Common challenges included resource and sustainability-related aspects such as financial constraints, limited lab equipment for diagnosis, and inadequate government commitment. Significant barriers also encompassed physical/geographical challenges like difficulty accessing remote areas, and inadequate logistical support and transportation. Seven themes emerged to enhance patient outreach: resource mobilization; awareness-raising and advocacy; knowledge and capacity building; collaboration and partnership; decentralization of services; improved logistical support and infrastructure; utilization of technology and innovation; and financial aid and incentives. CONCLUSION: Multistakeholder collaboration, coupled with secured government commitment, is crucial for improving global outreach, diagnosis rates, and access to care for individuals with IBD. Customized outreach programs should consider regional contexts, financial constraints, and prioritize innovation.

3D delayed-enhanced magnetic resonance sequences improve conducting channel delineation prior to ventricular tachycardia ablation.

AIMS: Non-invasive depiction of conducting channels (CCs) is gaining interest for its usefulness in ventricular tachycardia (VT) ablation. The best imaging approach has not been determined. We compared characterization of myocardial scar with late-gadolinium enhancement cardiac magnetic resonance using a navigator-gated 3D sequence (3D-GRE) and conventional 2D imaging using either a single shot inversion recovery steady-state-free-precession (2D-SSFP) or inversion-recovery gradient echo (2D-GRE) sequence. METHODS AND RESULTS: We included 30 consecutive patients with structural heart disease referred for VT ablation. Preprocedural myocardial characterization was conducted in a 3 T-scanner using 2D-GRE, 2D-SSFP and 3D-GRE sequences, yielding a spatial resolution of 1.4 × 1.4 × 5 mm, 2 × 2 × 5 mm, and 1.4 × 1.4 × 1.4 mm, respectively. The core and border zone (BZ) scar components were quantified using the 60% and 40% threshold of maximum pixel intensity, respectively. A 3D scar reconstruction was obtained for each sequence. An electrophysiologist identified potential CC and compared them with results obtained with the electroanatomic map (EAM). We found no significant differences in the scar core mass between the 2D-GRE, 2D-SSFP, and 3D-GRE sequences (mean 7.48 ± 6.68 vs. 8.26 ± 5.69 and 6.26 ± 4.37 g, respectively, P = 0.084). However, the BZ mass was smaller in the 2D-GRE and 2D-SSFP than in the 3D-GRE sequence (9.22 ± 5.97 and 9.39 ± 6.33 vs. 10.92 ± 5.98 g, respectively; P = 0.042). The matching between the CC observed in the EAM and in 3D-GRE was 79.2%; when comparing the EAM and the 2D-GRE and the 2D-SSFP sequence, the matching decreased to 61.8% and 37.7%, respectively. CONCLUSION: 3D scar reconstruction using images from 3D-GRE sequence improves the overall delineation of CC prior to VT ablation.

Exploring the neural basis of non-invasive prehabilitation in brain tumour patients: An fMRI-based case report of language network plasticity.

Primary brain neoplasms are associated with elevated mortality and morbidity rates. Brain tumour surgery aims to achieve maximal tumour resection while minimizing damage to healthy brain tissue. Research on Neuromodulation Induced Cortical Prehabilitation (NICP) has highlighted the potential, before neurosurgery, of establishing new brain connections and transfer functional activity from one area of the brain to another. Nonetheless, the neural mechanisms underlying these processes, particularly in the context of space-occupying lesions, remain unclear. A patient with a left frontotemporoinsular tumour underwent a prehabilitation protocol providing 20 sessions of inhibitory non-invasive neuromodulation (rTMS and multichannel tDCS) over a language network coupled with intensive task training. Prehabilitation resulted in an increment of the distance between the tumour and the language network. Furthermore, enhanced functional connectivity within the language circuit was observed. The present innovative case-study exposed that inhibition of the functional network area surrounding the space-occupying lesion promotes a plastic change in the network's spatial organization, presumably through the establishment of novel functional pathways away from the lesion's site. While these outcomes are promising, prudence dictates the need for larger studies to confirm and generalize these findings.

Evaluation of the Orthotropic Behavior in an Auxetic Structure Based on a Novel Design Parameter of a Square Cell with Re-Entrant Struts.

In this research, a three-dimensional auxetic configuration based on a known re-entrant cell is proposed. The 3D auxetic cell is configured from a new design parameter that produces an internal rotation angle to its re-entrant elements to study elastic properties in its three orthogonal directions. Through a topological analysis using Timoshenko beam theory, the bending of its re-entrant struts is modeled as a function of the new design parameter to manipulate Poisson's ratio and Young's modulus. Experimental samples were fabricated using a fused filament fabrication system using ABS and subsequently tested under quasi-static compression and bending tests. Additionally, an orthotropy factor is applied that allows for measuring the deviation between the mechanical properties of each structure. The experimental results validate the theoretical design and show that this new unit cell can transmit an orthotropic mechanical behavior to the macrostructure. In addition, the proposed structure can provide a different bending stiffness behavior in up to three working directions, which allows the application under different conditions of external forces, such as a prosthetic ankle.

Meditation-induced effects on whole-brain structural and effective connectivity.

In the past decades, there has been a growing scientific interest in characterizing neural correlates of meditation training. Nonetheless, the mechanisms underlying meditation remain elusive. In the present work, we investigated meditation-related changes in functional dynamics and structural connectivity (SC). For this purpose, we scanned experienced meditators and control (naive) subjects using magnetic resonance imaging (MRI) to acquire structural and functional data during two conditions, resting-state and meditation (focused attention on breathing). In this way, we aimed to characterize and distinguish both short-term and long-term modifications in the brain's structure and function. First, to analyze the fMRI data, we calculated whole-brain effective connectivity (EC) estimates, relying on a dynamical network model to replicate BOLD signals' spatio-temporal structure, akin to functional connectivity (FC) with lagged correlations. We compared the estimated EC, FC, and SC links as features to train classifiers to predict behavioral conditions and group identity. Then, we performed a network-based analysis of anatomical connectivity. We demonstrated through a machine-learning approach that EC features were more informative than FC and SC solely. We showed that the most informative EC links that discriminated between meditators and controls involved several large-scale networks mainly within the left hemisphere. Moreover, we found that differences in the functional domain were reflected to a smaller extent in changes at the anatomical level as well. The network-based analysis of anatomical pathways revealed strengthened connectivity for meditators compared to controls between four areas in the left hemisphere belonging to the somatomotor, dorsal attention, subcortical and visual networks. Overall, the results of our whole-brain model-based approach revealed a mechanism underlying meditation by providing causal relationships at the structure-function level.

Characterizing the Dynamical Complexity Underlying Meditation.

Over the past 2,500 years, contemplative traditions have explored the nature of the mind using meditation. More recently, neuroimaging research on meditation has revealed differences in brain function and structure in meditators. Nevertheless, the underlying neural mechanisms are still unclear. In order to understand how meditation shapes global activity through the brain, we investigated the spatiotemporal dynamics across the whole-brain functional network using the Intrinsic Ignition Framework. Recent neuroimaging studies have demonstrated that different states of consciousness differ in their underlying dynamical complexity, i.e., how the broadness of communication is elicited and distributed through the brain over time and space. In this work, controls and experienced meditators were scanned using functional magnetic resonance imaging (fMRI) during resting-state and meditation (focused attention on breathing). Our results evidenced that the dynamical complexity underlying meditation shows less complexity than during resting-state in the meditator group but not in the control group. Furthermore, we report that during resting-state, the brain activity of experienced meditators showed higher metastability (i.e., a wider dynamical regime over time) than the one observed in the control group. Overall, these results indicate that the meditation state operates in a different dynamical regime compared to the resting-state.

Improved tools and strategies for the prevention and control of arboviral diseases: A research-to-policy forum.

BACKGROUND: Research has been conducted on interventions to control dengue transmission and respond to outbreaks. A summary of the available evidence will help inform disease control policy decisions and research directions, both for dengue and, more broadly, for all Aedes-borne arboviral diseases. METHOD: A research-to-policy forum was convened by TDR, the Special Programme for Research and Training in Tropical Diseases, with researchers and representatives from ministries of health, in order to review research findings and discuss their implications for policy and research. RESULTS: The participants reviewed findings of research supported by TDR and others. Surveillance and early outbreak warning. Systematic reviews and country studies identify the critical characteristics that an alert system should have to document trends reliably and trigger timely responses (i.e., early enough to prevent the epidemic spread of the virus) to dengue outbreaks. A range of variables that, according to the literature, either indicate risk of forthcoming dengue transmission or predict dengue outbreaks were tested and some of them could be successfully applied in an Early Warning and Response System (EWARS). Entomological surveillance and vector management. A summary of the published literature shows that controlling Aedes vectors requires complex interventions and points to the need for more rigorous, standardised study designs, with disease reduction as the primary outcome to be measured. House screening and targeted vector interventions are promising vector management approaches. Sampling vector populations, both for surveillance purposes and evaluation of control activities, is usually conducted in an unsystematic way, limiting the potentials of entomological surveillance for outbreak prediction. Combining outbreak alert and improved approaches of vector management will help to overcome the present uncertainties about major risk groups or areas where outbreak response should be initiated and where resources for vector management should be allocated during the interepidemic period. CONCLUSIONS: The Forum concluded that the evidence collected can inform policy decisions, but also that important research gaps have yet to be filled.

Associations of quality of life, pain, and self-reported arthritis with age, employment, bleed rate, and utilization of hemophilia treatment center and health care provider services: results in adults with hemophilia in the HERO study.

INTRODUCTION: Severe hemophilia and subsequent hemophilic arthropathy result in joint pain and impaired health-related quality of life (HRQoL). Assessment of HRQoL in persons with hemophilia (PWH), including underlying factors that drive HRQoL differences, is important in determining health care resource allocation and in making individualized clinical decisions. AIM: To examine potential associations between HRQoL, pain interference, and self-reported arthritis and age, employment, activity, bleed frequency, and hemophilia treatment center and health care professional utilization. METHODS: PWH (age ≥18 years) from ten countries completed a 5-point Likert scale on pain interference over the previous 4 weeks, the EQ-5D-3L scale (mobility, usual activities, self-care, pain/discomfort, anxiety/depression) including a health-related visual analog scale (0-100, coded as an 11-point categorical response). RESULTS: Pain interference (extreme/a lot) was higher in PWH aged >40 years (31%) compared to those aged 31-40 years (27%) or ≤30 years (21%). In an analysis of eight countries with home treatment, PWH who reported EQ-5D mobility issues were less likely to be employed (53% vs 79%, with no mobility issues). Median annual bleed frequency increased with worsening EQ-5D pain or discomfort. The percentage of PWH with inhibitors reporting visual analog scale scores of 80-90-100 was lower (20%) than those without inhibitors (34%). Median bleed frequency increased with pain. Globally, nurse and social worker involvement increased with disability and pain; physiotherapist utilization was moderate regardless of the extent of disability or pain. CONCLUSION: Increased disability and pain were associated with increased age, lower employment, higher reported bleed frequency, and lower HRQoL.

CMR-guided approach to localize and ablate gaps in repeat AF ablation procedure.

OBJECTIVES: The aim of this study was to test the feasibility and usefulness of a new delayed-enhancement cardiac magnetic resonance (DE-CMR)-guided approach to ablate gaps in redo procedures. BACKGROUND: Recurrences of atrial fibrillation (AF) after pulmonary vein isolation (PVI) may be related to gaps at the ablation lines. DE-CMR allows identification of radiofrequency lesions and gaps (CMR gaps). METHODS: Fifteen patients undergoing repeated AF ablations were included (prior procedure was PVI in all patients and roof-line ablation in 8 patients). Pre-procedure 3-dimensional (3D) DE-CMR was performed with a respiratory-navigated (free-breathing) and electrocardiographically gated inversion-recovery gradient-echo sequence (voxel size 1.25 × 1.25 × 2.5 mm). Endocardium and epicardium were manually segmented to create a 3D reconstruction (DE-CMR model). A pixel signal intensity map was projected on the DE-CMR model and color-coded (thresholds 40 ± 5% and 60 ± 5% of maximum intensity). The DE-CMR model was imported into the navigation system to guide the ablation of CMR gaps, with the operator blinded to electrical data. Fifteen conventional procedures were used as controls to compare procedural duration, radiofrequency, and fluoroscopy times. RESULTS: Fifteen patients (56 pulmonary veins [PVs]; 57 ± 8 years of age; 9 with paroxysmal AF) were analyzed. In total, 67 CMR gaps were identified around PVs (mean 4.47 gaps/patient; median length 13.33 mm/gap) and 9 at roof line. All of the electrically reconnected PVs (87.5%) had CMR gaps. The site of electrical PV reconnection (assessed by circular mapping catheter) matched with a CMR gap in 79% of PVs. CMR-guided ablation led to reisolation of 95.6% of reconnected PVs (median radiofrequency time of 13.3 [interquartile range: 7.5 to 21.7] min/patient) and conduction block through the roof line in all patients (1.4 [interquartile range: 0.7 to 3.1] min/patient). Compared with controls, the CMR-guided approach shortened radiofrequency time (1,441 ± 915 s vs. 930 ± 662 s; p = 0.026) but not the procedural duration or fluoroscopy time. CONCLUSIONS: DE-CMR can successfully guide repeated PVI procedures by accurately identifying and localizing gaps and may reduce procedural duration and radiofrequency application time.