Intravesical administration of durvalumab to patients with high risk non muscle invasive bladder cancer after BCG failure. A phase II trial by the Hellenic GU Cancer Group

Introduction & Objectives: Patients with high risk non muscle invasive bladder cancer (NMIBC) who experience BCG failure have limited bladder preserving treatment options as radical cystectomy currently represents the standard therapeutical approach. Systematic immunotherapy (IO) has changed the landscape in advanced bladder cancer and is currently being investigated in NMIBC. Based on the hypothesis that intravesical administration will not be related with severe adverse events, we evaluated the role of intravesically administered durvalumab in NMIBC patients after BCG failure. Material(s) and Method(s): An open label, single-arm, multi-center, phase II clinical trial was conducted. A run-in phase had the objective to determine the maximum tolerated dose (MTD) of durvalumab and to exclude a detrimental effect on disease relapse by this strategy. Durvalumab was administered for a total of 6 instillations per patient at consecutive levels of 500, 750 and 1000 mg. Phase II has as primary end point the 1-year high-grade-relapse-free (HGRF)-rate. Secondary endpoints included toxicity, and high-grade progression-free rat at 1, 3 and 6 months after treatment. Result(s): Thirty patients were enrolled (run in phase: 9, phase II: 21). One patient withdrew consent prior to receiving study treatment, so 29 patients were included in efficacy and toxicity analyses. Mean age was 66.5 years. MTD of durvalumab was set at 1000 mg as no dose related toxicities (DLTs) occurred at any level studied. Three of 9 patients included in the run-in phase (33.3%) were tumor free one month after the last durvalumab instillation, therefore, the null hypothesis was rejected by the futility analysis. Western blot showed that durvalumab remained stable in urine during instillation. One patient died from Covid-19, 3 months after the last durvalumab administration. All patients concluded at least 1 year follow up. One-year HGRF rate was 34.6%. HGRF rates at 1, 3 and 6 months was 73%, 65.3% and 50% respectively. Five patients (17%) experienced a T2 or above disease relapse. Five out of the six patients who received 500mg or 750mg of durvalumab relapsed within 1 year. When efficacy analyses were restricted to patients receiving 1000mg of durvalumab, 1-year HGRF rate was 35%. Interestingly, 2 out of 2 patients with only CIS disease at baseline experienced a tumor complete response, which was durable and was maintained at least for a year. No severe adverse events were noted. The most common adverse event was Grade 1 hematuria. Conclusion(s): Intravesical IO using durvalumab was proved to be feasible with an excellent safety profile. Oncological results seem to be promising and comparable with other bladder preserving strategies in BCG failure with the advantage of a better safety profile. Further study of intravesical IO in high-risk patients with NMIBC after BCG failure is warranted.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Ventilation requirements and energy aspects: The case of hospitals

Energy building design today aims to ensure thermal comfort and indoor air quality;this concern has been increased, given the recent SARS-CoV-2 pandemic. The proposed work investigates the effect of increased natural ventilation on energy requirements, ensuring low CO2 levels and acceptable Indoor Air Quality (IAQ) in general. The case of hospitals was chosen because of the stringent IAQ requirements they raise as a result of the burdened (physical, chemical, biological) indoor environment, as well as the vulnerable health of the patients. The current energy analysis was carried out in patient wards, waiting rooms, and operating rooms. The proposed correlation between IAQ and energy is infrequent in the relevant literature, especially for the case of hospitals. Different scenarios regarding the ventilation mode are examined, including pure natural ventilation, natural ventilation combined with air cleaners, as well as mechanical ventilation. According to the results, improvement of the air quality leads to higher energy demand;this is the case of mechanical ventilation, noting that not properly designed natural ventilation techniques may lead to high energy consumption, without ensuring acceptable IAQ. Air cleaners can contribute towards better environment, potentially decreasing ventilation requirements;the issue of fresh air adequacy has to be examined though. The demonstrated methodological analysis and results can help the designer to investigate the efficiency of different ventilation modes, involving the effect of thermal envelope, geometrical and operation parameters, towards the energy requirements minimization and IAQ quality maximization. © Published under licence by IOP Publishing Ltd.

Urology residency training during the pandemic. A review of the current literature

Introduction & Objectives: On March 11, 2020, WHO declared Covid-19 as a pandemic placing a significant strain on the worldwide healthcare system. Although urology does not stand at the frontline of care for patients with Covid-19, every practicing urologist has been affected by the global outbreak. The objective of this review is to evaluate the impact of Covid-19 pandemic on urology residency training programs. Materials & Methods: We performed a literature review of the current evidence on urology residency training during the Covid-19 pandemic. Relevant databases (MEDLINE, Scopus, Cochrane Library) were searched (until June 2021) and the main study-inclusion criterion was the presence of residents’ or directors’ opinion on their residency training program during the Covid-19 crisis. Results: Literature search identified 72 articles. 14 studies comprising a total of more than 2500 residents were eligible for inclusion in the analysis. During the pandemic, learning activities carried out by urology residents suffered a forced modulation. There has been a decrease in operation volume especially in procedures in which residents were directly involved. Similarly, there was a decline in most of the academic activities worldwide. Furthermore, the negative impact on residents’ mental well-being and lifestyle is reported by many studies. On the other hand, the lockdown stressed the opportunity to review the current training system and to increase the implementation of tools such as telemedicine and smart-learning surgical skill training programs. Conclusions: Covid-19 pandemic has resulted in significant changes in urology residency programs worldwide, with a negative impact on matters such as surgical training and academic activities. Residents’ well-being and mental health is also risked. Hopefully, this unprecedented situation has generated new online learning modalities and technological innovations in the field of training in urology

Business Continuity During the COVID-19 Pandemic Era: Surviving and Improving the Quality Process Management System

Worldwide health and the global economy have been heavily damaged by the COVID-19 pandemic, with business continuity being the primary issue of every company operating in the health industry. A critical instrument for enterprises' survival is the establishment of a business continuity management system that enables them to manage risks, discover opportunities created by the pandemic, and secure their continuity. The purpose of this paper is to examine how a pharmaceutical firm may ensure business continuity by adopting ISO 22301:2019 in parallel with the existing ISO 9001:2015 quality standard, as well as the similarities and differences between the two management standards. According to the results, the pharmaceutical company, whose case was studied, managed to create an effective action plan in order to mitigate at an acceptable level the identified risks, to maintain its business continuity and to ensure the quality of the product and the health of the patients and its employees. © 2022, World Scientific and Engineering Academy and Society. All rights reserved.

European Union Digital Education quality standard framework and companion evaluation toolkit

The Covid-19 pandemic positioned digital education in a new light. The need for educational institutions to develop strategies, standards and establish quality assurance across digital education became even more evident. This paper describes the four-step process of designing an interactive European Union (EU) Digital Education Quality Standard Framework and Companion Evaluation Toolkit to guide the design, delivery and evaluation of effective digital education. (1) A review of literature of existing digital education frameworks and models is presented. (2) Variables and sub-variables inherent in designing, delivering and evaluating effective digital education are identified. (3) Next the variables and sub-variables in the framework are defined. (4) The process of designing the interactive framework diagram is described with the companion evaluation toolkit outlined. The proposed framework is flexible and applicable to entities and audiences regardless of where they are in the online learning adoption process. [ABSTRACT FROM AUTHOR] Copyright of Open Learning is the property of Routledge and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)