| 1. |
- Razavi, Homie A., et al.
(författare)
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Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries
- 2023
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Ingår i: JOURNAL OF HEPATOLOGY. - : Elsevier. - 0168-8278 .- 1600-0641. ; 79:2, s. 576-580
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV in-fections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Ac-curate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This re-quires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive in-dividuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.
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| 2. |
- Imel, Erik A., et al.
(författare)
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Burosumab versus conventional therapy in children with X-linked hypophosphataemia : a randomised, active-controlled, open-label, phase 3 trial
- 2019
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 393:10189, s. 2416-2427
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Tidskriftsartikel (refereegranskat)abstract
- Background: X-linked hypophosphataemia in children is characterised by elevated serum concentrations of fibroblast growth factor 23 (FGF23), hypophosphataemia, rickets, lower extremity bowing, and growth impairment. We compared the efficacy and safety of continuing conventional therapy, consisting of oral phosphate and active vitamin D, versus switching to burosumab, a fully human monoclonal antibody against FGF23, in paediatric X-linked hypophosphataemia.Methods: In this randomised, active-controlled, open-label, phase 3 trial at 16 clinical sites, we enrolled children with X-linked hypophosphataemia aged 1-12 years. Key eligibility criteria were a total Thacher rickets severity score of at least 2.0, fasting serum phosphorus lower than 0.97 mmol/L (3.0 mg/dL), confirmed PHEX (phosphate-regulating endopep-tidase homolog, X-linked) mutation or variant of unknown significance in the patient or a family member with appropriate X-linked dominant inheritance, and receipt of conventional therapy for at least 6 consecutive months for children younger than 3 years or at least 12 consecutive months for children older than 3 years. Eligible patients were randomly assigned (1: 1) to receive either subcutaneous burosumab starting at 0.8 mg/kg every 2 weeks (burosumab group) or conventional therapy prescribed by investigators (conventional therapy group). Both interventions lasted 64 weeks. The primary endpoint was change in rickets severity at week 40, assessed by the Radiographic Global Impression of Change global score. All patients who received at least one dose of treatment were included in the primary and safety analyses. The trial is registered with ClinicalTrials.gov, number NCT02915705.Findings: Recruitment took place between Aug 3, 2016, and May 8, 2017. Of 122 patients assessed, 61 were enrolled. Of these, 32 (18 girls, 14 boys) were randomly assigned to continue receiving conventional therapy and 29 (16 girls, 13 boys) to receive burosumab. For the primary endpoint at week 40, patients in the burosumab group had significantly greater improvement in Radiographic Global Impression of Change global score than did patients in the conventional therapy group (least squares mean +1.9 [SE 0.1] with burosumab vs +0.8 [0.1] with conventional therapy; difference 1.1, 95% CI 0.8-1.5; p<0.0001). Treatment-emergent adverse events considered possibly, probably, or definitely related to treatment by the investigator occurred more frequently with burosumab (17 [59%] of 29 patients in the burosumab group vs seven [22%] of 32 patients in the conventional therapy group). Three serious adverse events occurred in each group, all considered unrelated to treatment and resolved.Interpretation: Significantly greater clinical improvements were shown in rickets severity, growth, and biochemistries among children with X-linked hypophosphataemia treated with burosumab compared with those continuing conventional therapy. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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| 3. |
- Nilsson, Ola, 1970-, et al.
(författare)
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Burosumab Improved Rickets, Phosphate Metabolism, and Clinical Outcomes Compared to Conventional Therapy in Children with X-Linked Hypophosphatemia (XLH) - A Randomized Controlled Phase 3 Study
- 2018
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 90:Suppl.1, s. 57-58
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In children with XLH, high circulating levels of FGF23 cause hypophosphatemia with consequent rickets, skeletal deformities, and growth impairment. Conventional therapy consists of multiple daily doses of oral phosphate and active vitamin D (Pi/D). Burosumab is a fully human monoclonal antibody against FGF23 indicated for the treatment of XLH.In the active-control study CL301 (NCT02915705), 61 children with XLH (1-12 years old) were randomized (1:1) to receive subcutaneous burosumab starting at 0.8 mg/kg every 2 weeks (Q2W) or Pi/D as prescribed by investigators. Eligibility criteria included a Total Rickets Severity Score (RSS) ≥2.0 and prior receipt of Pi/D. The primary endpoint was healing of rickets at Week 40 assessed by radiologists blinded to treatment using the Radiographic Global Impression of Change (RGI-C).At Week 40, burosumab significantly improved rickets compared with Pi/D (RGI-C global score least squares [LS] mean ± SE: +1.92 ± 0.11 vs +0.77 ± 0.11; p<0.0001). More subjects in the burosumab group had substantial healing (RGI-C ≥+2.0) at Week 40, compared with the Pi/D group (21/29, 72% vs 2/32, 6%; odds ratio of 39.1, p<0.0001). Additional evidence for improvement of rickets included decreased Total RSS (LS mean ± SE change, burosumab vs Pi/D: -2.04 ± 0.145 vs -0.71 ± 0.138; p<0.0001), decreased alkaline phosphatase (-131 ± 13 vs -35 ± 19; p<0.0001), and improved RGI-C lower limb deformity score (+0.62 ± 0.12 vs +0.21 ± 0.12; p=0.020). At Week 40, increases in serum phosphorous (p<0.0001) and TmP/GFR (p<0.0001) were significantly greater with burosumab compared with Pi/D. Standing height Z-score increased in both treatment groups from baseline to Week 40 with an LS mean change of +0.15 (95% CI: 0.05, 0.25) for burosumab and +0.08 (-0.02, 0.19) for Pi/D. Percent predicted distance walked in six minutes increased with burosumab (Baseline to Week 40: 62% to 72%) and was unchanged with Pi/D (76% to 75%). Pre-defined adverse events (AEs) of interest, including hypersensitivity and injection site reaction, were higher in the burosumab group, but were mild to moderate in severity overall, with no discontinuations. There were 4 serious AEs (3 burosumab, 1 Pi/D); none were treatment-related and all resolved.In this randomized Phase 3 clinical trial, burosumab Q2W re-sulted in significantly greater improvements in rickets and phosphate metabolism compared with conventional therapy in 1-12 year-old children with XLH.
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| 4. |
- Persson, Martin, 1970-
(författare)
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Semantic mapping using virtual sensors and fusion of aerial images with sensor data from a ground vehicle
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, semantic mapping is understood to be the process of putting a tag or label on objects or regions in a map. This label should be interpretable by and have a meaning for a human. The use of semantic information has several application areas in mobile robotics. The largest area is in human-robot interaction where the semantics is necessary for a common understanding between robot and human of the operational environment. Other areas include localization through connection of human spatial concepts to particular locations, improving 3D models of indoor and outdoor environments, and model validation. This thesis investigates the extraction of semantic information for mobile robots in outdoor environments and the use of semantic information to link ground-level occupancy maps and aerial images. The thesis concentrates on three related issues: i) recognition of human spatial concepts in a scene, ii) the ability to incorporate semantic knowledge in a map, and iii) the ability to connect information collected by a mobile robot with information extracted from an aerial image. The first issue deals with a vision-based virtual sensor for classification of views (images). The images are fed into a set of learned virtual sensors, where each virtual sensor is trained for classification of a particular type of human spatial concept. The virtual sensors are evaluated with images from both ordinary cameras and an omni-directional camera, showing robust properties that can cope with variations such as changing season. In the second part a probabilistic semantic map is computed based on an occupancy grid map and the output from a virtual sensor. A local semantic map is built around the robot for each position where images have been acquired. This map is a grid map augmented with semantic information in the form of probabilities that the occupied grid cells belong to a particular class. The local maps are fused into a global probabilistic semantic map covering the area along the trajectory of the mobile robot. In the third part information extracted from an aerial image is used to improve the mapping process. Region and object boundaries taken from the probabilistic semantic map are used to initialize segmentation of the aerial image. Algorithms for both local segmentation related to the borders and global segmentation of the entire aerial image, exemplified with the two classes ground and buildings, are presented. Ground-level semantic information allows focusing of the segmentation of the aerial image to desired classes and generation of a semantic map that covers a larger area than can be built using only the onboard sensors.
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