Bluebird Bio (France)

Care coordination is an important strategy for addressing patient needs and improving outcomes of care. The Minnesota Care Coordination Effectiveness Study sought to better understand the perspectives and experiences of clinicians/clinic leaders regarding the value, barriers, and facilitators for care coordination in primary care. We conducted semi-structured interviews with 18 clinic managers, physicians, and advanced practice clinicians. Data were analyzed using a directed content analysis approach. Five themes arose in the interviews: financial issues were perceived as a primary barrier to care coordination; participants valued care coordination as an important asset; they employed significant variation in how care coordination was structured; they identified both medical and social needs of patients as important; and care coordinators' background, experience, and integration were viewed as critical to program success. Care coordination received strong support from clinicians and clinic leaders who viewed it as a valuable component of successful care delivery.

Abstract Presentation Date: 6/8/2024 Presentation Start Time: 8:45:00 AM Background Lovotibeglogene autotemcel (lovo-cel) gene therapy uses autologous transplantation of hematopoietic stem and progenitor cells (HSPC) transduced with the BB305 lentiviral vector encoding a modified β-globin gene, which produces an anti-sickling hemoglobin (Hb), HbAT87Q. The phase 1/2 HGB-206 (NCT02140554) and phase 3 HGB-210 (NCT04293185) studies of lovo-cel are the largest clinical trials of gene therapy in sickle cell disease (SCD) to date. We report efficacy and safety from these studies, including the first data from adult and pediatric patients (age 12 to < 18 years) in HGB-210, and HRQOL data from HGB-206. Methods This analysis includes patients from HGB-206 Group C and HGB-210 who received lovo-cel using the current HSPC mobilization and manufacturing process. Patients with SCD and recurrent severe vaso-occlusive events (VOEs) or history of overt stroke underwent plerixafor mobilization and apheresis followed by myeloablative busulfan conditioning and lovo-cel infusion. After 24 months of follow-up post lovo-cel infusion, patients enrolled in the long-term study LTF-307 (NCT04628585). Lab evaluations, SCD-related outcomes (eg, resolution of VOEs), globin response (a composite endpoint evaluating HbAT87Q percentage and total Hb), and safety are reported up to 60 months. An independent Event Adjudication Committee confirmed VOEs met protocol criteria. HRQOL data from Patient-Reported Outcomes Measurement Information System (PROMIS)-57 domains of pain interference, fatigue, and pain intensity are reported up to 48 months. Results This analysis includes 47 patients (HGB-206 Group C, n = 36; HGB-210, n = 11; male, 59.6%; median [range] age, 23 y [12-38]) who received a lovo-cel infusion as of Feb 13, 2023. Median (range) follow-up was 35.5 months (0.3-61.0). Median (range) time to neutrophil and platelet engraftment was 20 days (12-35) and 35 days (19-136). Peripheral blood vector copy number remained stable (median >1 c/dg through follow-up). Median HbAT87Q levels were ≥4.5 g/dL from 6 months post infusion to last study visit. Median (range) total Hb level increased from 8.7 g/dL (6.1-12.5) at relative baseline to 11.8 g/dL (8.4-15.0) at last visit; median percent HbAT87Q of nontransfused total Hb was ≈40% or more (Figure 1). Of 34 evaluable patients (ie, ≥18 months follow-up and ≥4 VOEs in the 2 years before enrollment), 30 (88.2%) and 32 (94.1%) had complete resolution of VOEs and severe VOEs during the 6-18 months post infusion, vs a median (range) of 3.5 (1.5-16.5) and 3.0 (0.5-13.0) events/year in the 2 years before enrollment. Additional efficacy analyses in subgroups (eg, stroke history, α-globin genotype) will be presented. Among patients who had globin response or who had ≥18 months follow-up (n = 38), 33 (86.8%) achieved globin response. Hemolysis markers (eg, reticulocytes, total bilirubin, lactate dehydrogenase) approached normal levels. Among all 47 patients, 44 (93.6%) had ≥1 AE of grade ≥3 after lovo-cel infusion; the most common of which were stomatitis (33 [70.2%] patients) and thrombocytopenia (28 [59.6%]). Serious AEs were reported for 26 (55.3%) patients, the most common of which was chronic pain/acute exacerbation of chronic pain (3 [6.4%]; 2 chronic neuropathic pain and 1 chronic pain associated with anxiety). One patient with -α3.7/-α3.7 genotype diagnosed with myelodysplastic syndrome had stable complete blood counts 30 months post infusion. No veno-occlusive liver disease, graft failure, replication-competent lentivirus, or vector-mediated insertional oncogenesis was observed. Lovo-cel treatment regimen largely reflected known side effects of HSPC collection and busulfan conditioning regimen. A total of 25 patients (all from HGB-206 Group C; age ≥18 y) had evaluable HRQOL data. Mean scores for PROMIS-57 domains of pain intensity, pain interference, and fatigue improved (ie, decreased) over time up to 48 months (Figure 2). Conclusions One-time treatment with lovo-cel resulted in sustained HbAT87Q production and near-complete resolution of VOEs and severe VOEs up to 18 months post treatment; the safety profile was consistent with underlying SCD and myeloablative conditioning. Patients reported sustained improvements in pain intensity, pain interference, and fatigue. Ongoing long-term follow-up will continue to provide important information on efficacy, safety, and patient experience post lovo-cel treatment.

Background and ObjectiveGene therapies for sickle cell disease (SCD) may offer meaningful benefits for patients and society. This study evaluated the cost-effectiveness of lovotibeglogene autotemcel (lovo-cel), a one-time gene therapy administered via autologous hematopoietic stem cell transplantation, compared with common care for patients in the United States (US) with SCD aged ≥ 12 years with ≥ 4 vaso-occlusive events (VOEs) in the past 24 months.MethodsWe developed a patient-level simulation model accounting for lovo-cel and SCD-related events, complications, and mortality over a lifetime time horizon. The pivotal phase 1/2 HGB-206 clinical trial (NCT02140554) served as the basis for lovo-cel efficacy and safety. Cost, quality-of-life, and other clinical data were sourced from HGB-206 data and the literature. Analyses were conducted from US societal and third-party payer perspectives. Uncertainty was assessed through probabilistic sensitivity analysis and extensive scenario analyses.ResultsPatients treated with lovo-cel were predicted to survive 23.84 years longer on average (standard deviation [SD], 12.80) versus common care (life expectancy, 62.24 versus 38.40 years), with associated discounted patient quality-adjusted life-year (QALY) gains of 10.20 (SD, 4.10) and direct costs avoided of $1,329,201 (SD, $1,346,446) per patient. Predicted societal benefits included discounted caregiver QALY losses avoided of 1.19 (SD, 1.38) and indirect costs avoided of $540,416 (SD, $262,353) per patient. Including lovo-cel costs ($3,282,009 [SD, $29,690] per patient) resulted in incremental cost-effectiveness ratios of $191,519 and $124,051 per QALY gained from third-party payer and societal perspectives, respectively. In scenario analyses, the predicted cost-effectiveness of lovo-cel also was sensitive to baseline age and VOE frequency and to the proportion of patients achieving and maintaining complete resolution of VOEs.ConclusionsOur analysis of lovo-cel gene therapy compared with common care for patients in the US with SCD with recurrent VOEs estimated meaningful improvements in survival, quality of life, and other clinical outcomes accompanied by increased overall costs for the health care system and for broader society. The predicted economic value of lovo-cel gene therapy was influenced by uncertainty in long-term clinical effects and by positive spillover effects on patient productivity and caregiver burden.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40273-024-01385-9.

Recent research in disaster informatics demonstrates a practical and important use case of artificial intelligence to save human lives and suffering during natural disasters based on social media contents (text and images). While notable progress has been made using texts, research on exploiting the images remains relatively under-explored. To advance image-based approaches, we propose MEDIC (https://crisisnlp.qcri.org/medic/index.html), which is the largest social media image classification dataset for humanitarian response consisting of 71,198 images to address four different tasks in a multi-task learning setup. This is the first dataset of its kind: social media images, disaster response, and multi-task learning research. An important property of this dataset is its high potential to facilitate research on multi-task learning, which recently receives much interest from the machine learning community and has shown remarkable results in terms of memory, inference speed, performance, and generalization capability. Therefore, the proposed dataset is an important resource for advancing image-based disaster management and multi-task machine learning research. We experiment with different deep learning architectures and report promising results, which are above the majority baselines for all tasks. Along with the dataset, we also release all relevant scripts (https://github.com/firojalam/medic).

The rapid aging of the population combined with the correlation between age and the increase in falls pushes us to create new ways to monitor the elderly. The privacy of radar data can respond to one of the weaknesses of existing technologies, but the huge amount of radar data to process becomes a challenge to process. We therefore introduce a first architecture allowing the processing of its data in real time. The radar technology used is an off-the-shelf Frequency Modulated Continuous Wave radar Ancortek (SDR 980AD2). It is followed by a pre-processing chain composed of Fast Fourier Transform, Filter and Short Time Fourier Transform to obtain time-velocity maps or spectrograms allowing the extraction of features from gait and human activities. An encouraging implementation (using SIMD logic) on Jetson Xavier allows us to move to data stream processing. Continuous monitoring of the subject will save lives, minimize injuries, reduce anxiety and prevent post-fall syndrome (PDS).

Abstract Sickle cell disease (SCD) is one of the most prevalent serious genetic conditions in England. Increased patient numbers and more intensive management is thought to have resulted in higher demand for hospital services. This study attempts to quantify this increase.Data from the Hospital Episodes Statistics (HES) Admitted Patient Care (APC) and Outpatient (OP) datasets for patients with a diagnosis of SCD during the 10-year period January 2009 to December 2018 were extracted. Two sub-groups were defined, ‘high crises’ and ‘high transfusions’, with all other patients assigned to the ‘other SCD’ group. Analysis of hospital resource use in the three sub-groups was undertaken. Overall patient numbers increased by 9.9% (9,615 to 10,570) and treatment costs by 82% (£41.9m to £76.4m) over the ten-year period. Disproportionately greater: patient numbers and costs were observed in the two sub-groups of interest. In the high crises sub-group, patient numbers increased by 43% (1,194 to 1,713) and treatments costs by 310% (£9.4m to £38.5m), with corresponding increases of 187% (205 to 589) and 236% (£2.8m to £9.4m) in the high transfusions patients sub-group.Prevalence of sickle cell disease in England continues to grow resulting in significant demand on NHS services. Patients categorised as high crises and high transfusions are consistently greater users of hospital resource and account for the majority of NHS hospital expenditure.

Acrodysostosis is a rare skeletal dysplasia caused by loss-of-function mutations in the regulatory subunit of protein kinase A (PRKAR1A). In a knock-in mouse model (PRKAR1Awt/mut) expressing one copy of the recurrent R368X mutation, we tested the effects of a rAAV9-CAG-human PRKR1A (hPRKAR1A) vector intravenously administered at 4 weeks of age. Caudal vertebrae and tibial diaphyses contained 0.52 ± 0.7 and 0.13 ± 0.3 vector genome per cell (VGC), respectively, at 10 weeks of age and 0.22 ± 0.04 and 0.020 ± 0.04 at 16 weeks while renal cortex contained 0.57 ± 0.14 and 0.26 ± 0.05 VGC. Vector-mediated hPRKAR1A expression was found in growth plate chondrocytes, osteoclasts, osteoblasts, and kidney tubular cells. Chondrocyte architecture was restored in the growth plates. Body length, tail length, and body weight were improved in vector treated PRKAR1Awt/mut mice, not the bone length of their limbs. These results provide one of the few proofs for gene therapy efficacy in a mouse model of chondrodysplasia. In addition, the increased urinary cAMP of PRKAR1Awt/mut mice was corrected almost to normal. In conclusion, gene therapy with hPRKAR1A improved skeletal growth and kidney dysfunction, the hallmarks of acrodysostosis in R368X mutated mice and humans.

Sektor Pariwisata merupakan salah satu penyumbang PDB serta devisa negara terbesar di Indonesia. Dalam upaya meningkatkan tingkat kunjungan wisatawan mancanegara ke Indonesia, pemerintah melalui kementrian pariwisata dan ekonomi kreatif melakukan usaha-usaha baik dalam bidang pembangunan destinasi, pembangunan industri,pembangunan pemasaran dengan menciptakan sebuah brand pariwisata bagi indonesia yaitu Wonderful Indonesia. Penelitian yang berjudul pengaruh brand “Wonderful Indonesia” dalam pembangunan industri pariwisata Indonesia merupakan sebuah penelitian yang menggunakan metode deskriptif kualitatif dengan menggunakan review literature yaitu membuat gambaran secara sistematis,faktual, dan akurat mengenai fakta serta hubungan antara fenomena yang diteliti. Penelitian ini bertujuan untuk menjelaskan pengaruh dari branding “Wonderful Indonesia” dalam pembangunan industri pariwisata dan mengetahui peran serta keterlibatan para lembaga non-pemerintah yang bekerjasama dalam pembangunan industri pariwisata. Sumber data dalam penelitian ini diperoleh dan dikumpulkan melalui data sekunder seperti buku, jurnal nasional maupun internasional, maupun internet. Berdasarkan hasil penelitian dapat disimpulkan bahwa upaya pemerintah untuk meningkatkan pembangunan industri di indonesia dilakukan dengan menciptakan strategi branding “Wonderful Indonesia” yang pemasarannya dilakukan melalui strategi DOT , BAS , POSE. Strategi branding ini berpengaruh dalam meningkatkan kunjungan wisatawan mancanegara ke Indonesia dan terus meningkat dari tahun ke tahun. Dengan meningkatnya kunjungan wisatawan mancanegara ke indonesia juga merupakan hasil kerjasama pihak pemerintah dengan lembaga sektor swasta seperti PT Blue Bird Tbk,Traveloka,dll. Keywords : Wonderful Indonesia, Pariwisata, Pembangunan

Image forgery or manipulation changes the contents of a set of original images to create a new image. Unfortunately, manipulated images become a growing concern with respect to spreading misinformation via image sharing in the social media. Despite the availability of a large number of automatic Image Forgery Detection (IFD) methods, their evaluation in real-world benchmarks seems to be limited due to the lack of diverse datasets. Moreover, the motifs behind the manipulation remains unclear. This research aims to address these issues by proposing a novel social media IFD database, called SMIFD-500, to evaluate the efficiency and generalizability of the IFD methods. The unique property of this dataset is the availability of the technical and social attributes in its ground truth annotations. These will benefit the scientific community to develop efficient methods by exploiting such annotations. Moreover, it provides interesting statistics, which highlights the motifs of image manipulation from social science perspective.