Takeda (Netherlands)

PURPOSE: Salvage options for patients who relapse after allogeneic stem-cell transplantation (allo-SCT) for acute myeloid leukemia (AML) and myelodysplasia (MDS) remain limited, and novel treatment strategies are required. Both lenalidomide (LEN) and azacitidine (AZA) possess significant antitumor activity effect in AML. Administration of LEN post-transplantation is associated with excessive rates of graft-versus-host disease (GVHD), but AZA has been shown to ameliorate GVHD in murine transplantation models. We therefore examined the tolerability and activity of combined LEN/AZA administration in post-transplantation relapse. PATIENTS AND METHODS: for 7 days) followed by escalating doses of LEN on days 10 to 30. Dose allocation and maximum tolerated dose (MTD) estimation were guided by a modified Bayesian continuous reassessment method (CRM). RESULTS: Sequential AZA and LEN therapy was well tolerated. The MTD of post-transplantation LEN, in combination with AZA, was determined as 25 mg daily. Three patients developed grade 2 to 4 GVHD. There was no GVHD-related mortality. Seven of 15 (47%) patients achieved a major clinical response after LEN/AZA therapy. CD8+ T cells demonstrated impaired interferon-γ/tumor necrosis factor-α production at relapse, which was not reversed during LEN/AZA administration. CONCLUSION: We conclude LEN can be administered safely post-allograft in conjunction with AZA, and this combination demonstrates clinical activity in relapsed AML/MDS without reversing biologic features of T-cell exhaustion. The use of a CRM model delivered improved efficiency in MTD assessment and provided additional flexibility. Combined LEN/AZA therapy represents a novel and active salvage therapy in patients who had relapsed post-allograft.

PURPOSE: To determine the burden of illness in patients with not adequately controlled chronic hypoparathyroidism receiving conventional therapy in Belgium and the Netherlands. METHODS: Data were generated from a cross-sectional, two-part online survey where endocrinologists from both countries and nephrologists from Belgium were invited by phone to participate. Part 1 included collecting data on general management of patients with hypoparathyroidism. In Part 2, physicians were requested to provide data on one or two current cases of patients with chronic hypoparathyroidism not adequately controlled on conventional therapy. Data collected included aetiology of hypoparathyroidism, clinical manifestations, comorbidities, results of laboratory and other investigations used for diagnosis and screening for complications, therapy received, and physician's perception of impaired quality of life (QoL). RESULTS: Thirty-six endocrinologists and 29 nephrologists from Belgium and 28 endocrinologists from the Netherlands participated in the survey. Data included clinical symptoms, biochemical parameters, and QoL for 97 current patients with not adequately controlled chronic hypoparathyroidism on conventional therapy. Median duration of not adequately controlled hypoparathyroidism was 2.2 years, range 0.17-20.0. Most patients had neuromuscular (85%) and/or neurological (67%) symptoms, 71% had abnormal biochemical parameters, 10% were overweight, and physicians perceived that 71% had impaired QoL. Most frequently reported comorbidities included hypertension (25%), renal comorbidity (20%), diabetes mellitus (12%), and dyslipidaemia (11%). CONCLUSION: Patients with chronic hypoparathyroidism not adequately controlled on conventional therapy experience a substantial burden of illness, mainly due to persistence of symptoms and presence of multiple comorbidities.

In the present note, we compile a checklist of all scorpion species recorded from Panama. A total of three families, five genera and 14 species are confirmed to occur in the country, and previous records of two other families, four genera, and nine species are discarded as misidentifications, mislabelings, or accidental introductions. Two Buthidae species are herein recorded for the first time from Panama: Tityus tayrona Lourenço, 1991 (so far known only from northern Colombia) and one apparently undescribed species of Ananteris Thorell, 1891.

Forty-two obese patients entered a placebo-controlled, double-blind 1-year study on dexfenfluramine, a serotonergic anorectic drug. Obesity was severe (mean body mass index 38.4 kg/m2), and of early onset and long duration. A mean of 8 attempts to lose weight was undertaken. After randomisation to 1 year of dexfenfluramine (dF) or placebo (non-dF) treatment, weight losses and changes in health risk indicators were investigated. Thereafter, continued follow-up by physician and dietician was encouraged. Seven patients withdrew, 4 (2 dF, 2 non-dF) because of dissatisfaction. Three patients (2dF, 1 non-dF) failed to lose weight. After initially greater weight losses in dF patients, the mean weight loss after 12 months was not significantly different, i.e. 12.8 kg in the dF vs. 8.6 kg in the non-dF group. Health risk indicators ameliorated to the same extent in both groups. Discontinuation of the active drug resulted in more weight gain [3.24 (dF) vs. 0.82 (non-dF) kg] in the following 2 months. After completion of the 1-year trial and the 2-month drug-free observation period, 8 of the 17 dF patients remained in follow-up for half a year, 5 for 1 year and 3 for 2 years. A respective 61%, 48% and 45% of the weight loss was maintained. The 13, 11 and 10 patients of the placebo group maintained 71%, 37% and 30% of the weight losses at half a year, 1 year and 2 years, respectively. Because of the modest weight loss, dexfenfluramine may not be a break-through in 1-year strategies.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND: Clinical trials investigating drugs for the acute treatment of hereditary angioedema attacks have assessed many different outcomes. This heterogeneity limits the comparability of trial results and may lead to selective outcome reporting bias and a high burden on trial participants. OBJECTIVE: To achieve consensus on a core outcome set composed of key outcomes that ideally should be used in all clinical efficacy trials involving the acute treatment of hereditary angioedema attacks. METHODS: We conducted a Delphi consensus study involving all relevant parties: patients with hereditary angioedema, hereditary angioedema expert clinicians and clinical researchers, pharmaceutical companies, and regulatory bodies. Two Internet-based survey rounds were conducted. In round 1, panelists indicated the importance of individual outcomes used in clinical trials on a 9-point Likert scale. Based on these results, a core outcome set was developed and voted on by panelists in round 2. RESULTS: A total of 58 worldwide panelists completed both rounds. The first round demonstrated high importance scores and substantial agreement among the panelists. In the second round, a consensus of 90% or greater was achieved on a core outcome set consisting of five key outcomes: change in overall symptom severity at one predetermined time point between 15 minutes and 4 hours after treatment, time to end of progression of all symptoms, the need for rescue medication during the entire attack, impairment of daily activities, and treatment satisfaction. CONCLUSIONS: This international study obtained a high level of consensus on a core outcome set for the acute treatment of hereditary angioedema attacks, consisting of five key outcomes.

The rapid growth of the online food delivery industry has led to a significant increase in the number of delivery riders navigating urban streets, predominantly using bikes and e-bikes. This growth has been accompanied by a concerning rise in crashes involving these riders, posing a critical challenge for city authorities and policymakers. Promoting safer riding behavior, such as choosing safer routes while delivering food, can potentially reduce crash risks. With this motivation, this paper aims to evaluate the effectiveness of strategies that encourage riders to choose safer routes and estimate the value riders place on reducing the risk of road crashes. The paper presents a stated preference experiment conducted with food delivery riders in Amsterdam and Copenhagen to assess two targeted strategies: ’safety information’ and ’monetary incentives’, designed to encourage riders toward selecting safer routes. The results from the route choice model show that presenting information about safety against crashes on different routes and offering monetary incentives can effectively motivate riders to choose safer routes, even if these are longer. The trade-offs riders make between safer and shorter routes were quantified by calculating the Value of Risk Reduction (VRR) and Willingness to Accept (WTA) indicators, which offer valuable insights into riders’ safety preferences. These indicators highlight how much riders value risk reduction and the compensation required to choose safer routes. Furthermore, the findings reveal that factors related to riders’ working arrangements and socio-demographic profiles significantly influence their route choice decisions. The paper concludes with a discussion about the practical challenges associated with implementing the strategies to enhance rider safety and proposing potential solutions that can be useful for food delivery platforms and policymakers. • Riders accept longer travel times if routes offer lower crash risk. • Cash incentives increase rider preference for safer routes. • A 10% crash risk drop is worth 1.85 extra travel minutes to riders. • Riders accept €1.80 for 10 extra minutes on safer delivery routes. • Practical barriers to improving rider safety are explored.

In the present note, we report on the occurrence of the genus Rhopalurus Thorell, 1898, in the southern Caribbean islands offshore Venezuela. The only published records are from Isla Margarita and Los Roques, but our study of new specimens (including an important collection assembled by the late Pieter Wagenaar Hummelinck) proved this genus to be widely distributed along several archipelagos such as Los Testigos, Los Frailes, and Los Hermanos, as well as the larger, separate islands of Margarita, Cubagua, La Tortuga, and Coche. These specimens are tentatively referred here to Rhopalurus laticauda Thorell, 1876, but their precise identity still warrants further study.

Purpose This study investigates the transformation of Vesteda, a Dutch residential real estate company, into a high-performance organization (HPO) over a decade-long period. It aims to provide theoretical insights into the application of the HPO framework in real estate and offer practical lessons for organizations seeking to enhance performance. Design/methodology/approach A longitudinal case study design was employed. Data were collected over ten years through six HPO diagnoses, semi-structured interviews with employees and managers, internal documentation and analysis of operational and financial metrics. Findings Vesteda improved its HPO score by 2.2 points and achieved a high-performance status within its sector. Key factors included leadership development, continuous improvement and employee engagement. Financial and operational indicators, including tenant satisfaction and rental income, also improved significantly. Originality/value This is one of the few longitudinal studies applying a validated performance framework in the real estate sector. It demonstrates how a structured transformation process can yield sustained organizational improvements and offers actionable insights for similar firms.

Abstract Background A core outcome set (COS) for patients with inflammatory bowel disease (IBD) was recently developed through a multi-stakeholder consensus in the Health Outcomes Observatory (H2O) project.(1) Recognizing the importance of data visualisation in enhancing disease management, the H2O website now provides a population-level dashboard to track quality and key performance indicators.(2) Patient-level dashboards are designed to support both healthcare providers (HCPs) and patients by facilitating individual health monitoring, encouraging patient-clinician dialogue, and supporting shared decision-making. This work aimed to develop a patient-level dashboard for HCPs to routinely monitor IBD patients, visualising data collected in the H2O IBD COS. Methods In November 2023, a core team comprising three public and four private sector researchers, was formed to coordinate the project. To guide discussions with target users, the lead academic centre developed a static dashboard template including all IBD COS variables. On- and offline feedback was gathered from target users and incorporated iteratively to refine the dashboard until consensus was achieved. Six patients from six countries reviewed the template, identifying unclear or missing outcomes essential for discussion during an outpatient clinic. Results A total of 15 HCPs and 7 academic researchers from 8 countries reviewed dashboard templates, providing feedback over two improvement rounds. In March 2024, consensus among target users was reached on the third version of the static dashboard (Figure). Key improvements included integrating medication tracking with graphical displays of biomarkers and patient-reported outcomes (PROs) related to disease activity, adding pop-up information on hover, and introducing graph customisation options. All consulted patients approved the final dashboard template without requiring additional adjustments. Conclusion We developed a patient-level dashboard for HCPs to support routine monitoring of IBD patients. The static template offers flexibility, allowing implementation teams to add customized information. The template is currently being transformed into a dynamic version for integration into the electronic health records of four academic hospitals. Additionally, the patient-level dashboard is currently being adjusted in close collaboration with patients to integrate into existing PRO collection tools, enabling patients to actively track their health progress themselves, and ensuring that patients and HCPs speak a common language to drive shared decision making. References 1)Fierens L, Carney N, Novacek G, van der Woude CJ, Siegmund B, Casellas F, Borruel N, Huberts AS, Sonnenberg E, Gerold N, Primas C, Hedin CRH, Stamm T, Julsgaard M, Fiorino G, Radice S, Zini MLL, Gross E, Sander C, Arijs I, Vakouftsi VR, Koltai T, Health Outcomes Observatory H O Patient Advisory Board For Inflammatory Bowel Diseases, Health Outcomes Observatory H O Steering Committee, Charlafti I, Ferrante M. A Core Outcome Set for Inflammatory Bowel Diseases: Development and Recommendations for Implementation in Clinical Practice Through an International Multi-stakeholder Consensus Process. J Crohns Colitis. 2024 Oct 15;18(10):1583-1595. doi: 10.1093/ecco-jcc/jjad195. 2)https://health-outcomes-observatory.eu/h2o-insights-center/

Abstract Recently, the second revision of the International Staging System (R2-ISS) has emerged as a prognostic tool for multiple myeloma (MM) and is known to be useful for prognostication at the time of diagnosis. Treatment outcomes for MM have significantly improved with the introduction of novel agents; however, eventual relapses nevertheless occur frequently, leading to refractory disease. Clonal evolution during relapse often results in high-risk cytogenetic abnormalities (HRCAs). Hence, a patient’s disease risk may change during their treatment course. We retrospectively analyzed whether R2-ISS influenced prognosis at treatment initiation in patients receiving anti-CD38 antibody, carfilzomib, and dexamethasone (Kd) treatments. HRCAs were examined from diagnosis to treatment initiation and considered positive if detected once. R2-ISS was recalculated at treatment initiation and defined as dynamic R2-ISS. Data from 60 patients who underwent the defined treatments were analyzed. The median observation period was 13.0 months, with a median progression-free survival (PFS) of 20.7 months. Median overall survival (OS) was not reached. Dynamic R2-ISS significantly stratified prognoses for both PFS and OS ( P = 0.00011 and 0.023, respectively). The median PFS for patients with dynamic R2-ISS IV was 4.4 months, and the median OS was 14.6 months, indicating extremely poor outcomes. Multivariate analysis considering disease progression at treatment initiation, triple-class refractory status, and dynamic R2-ISS showed that only R2-ISS significantly affected both PFS and OS ( P = 0.0041 and 0.019, respectively). Dynamic R2-ISS therefore shows potential as a prognostic tool in patients with MM who are treated via anti-CD38 antibody + Kd therapy.

<p>The occurence and impacts of disasters are increasing in many parts of the world. The increased complexity of disaster risk due to climate change, expected population growth and the increasing interconnectedness of disaster impacts across communities and economic sectors demonstrates the need to improve our ability to understand and model the impacts of consecutive disasters. These consecutive disasters can be described as disasters whose impacts overlap temporally and spatially while recovery from an earlier disaster is still underway. Several challenges affect our ability to account for the impacts of consecutive disasters and multi-hazard interactions, including extensive data requirements and a common focus on single-hazard risk.  </p><p> </p><p>Incorporating spatiotemporal dynamics of hazard, exposure and vulnerability is key to understanding drivers of risks and their interactions. In this study, we focus on the Philippines and generate an extensive dataset of multi-hazard events based on observed time series of disasters. We illustrate the potential applications of our dataset with an analysis of the inter-arrival time between hazard events and their impacts. The Philippines is located along the ‘Ring of fire’ and is one of the world’s most at risk countries of natural hazards includingearthquakes, tropical cyclones, landslides, and flooding. The study is carried out for the time period 1980-2019 and at two spatial scales: national and provincial. This dataset is further analysed to document the socio-economic impacts of consecutive disasters as well as the interdependencies and dynamics between multi-hazard events. This spatially and temporally consistent dataset can be used as input for future risk modelling effort to integrate the dynamics and impacts of consecutive disasters.</p>