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This paper describes two new modular ship design activities for graduate education at Delft University of Technology that have been developed during COVID. First, a new 2-hour hybrid format (in-person and virtual participation) game was designed to teach students modular design for offshore support vessels (OSVs). Second, an 8-week MSc-level ship design project was redeveloped to cover the design of a small fleet of modular OSVs for offshore wind. The paper discusses the drivers behind these new design educational activities, the details of the activities themselves, and concludes with lessons learned focused on improving graduate education for masters students studying ship design. © IMDC 2022. All right reserved.
ABSTRACT
Background: Vaccines have been an important strategy to control the SARS-CoV-2 pandemic. In The Netherlands two mRNA vaccines (BTN162b2, Pfizer-BioNTech;mRNA-1273, Moderna), and two adenovirus vector-based vaccines (ChAdOx1 nCoV-19, AstraZeneca;Ad26. COV2.S, Johnson & Johnson/Janssen) have been administered. In 2021, vaccination with the ChAdOx1 nCoV-19 was ceased in The Netherlands and other European countries due to the occurrence of thrombocytopenia and thromboembolic events. This new phenomenon was termed vaccine-induced thrombotic thrombocytopenia (VITT) and was clinically associated with thrombocytopenia and thrombosis at unusual sites, in particular cerebral venous sinus thrombosis (CVST). In addition, VITT was characterized by the presence of IgG-antibodies directed against platelet factor 4 (PF4). As PF4 appears to play a central role in the pathophysiology of VITT, it is recommended that the role of PF4 should be taken into account for VITT diagnostic testing. Aims: To characterize and define the patient population of clinically suspected VITT cases in The Netherlands from a diagnostics perspective. Methods: We describe a cohort of 283 clinically suspected VITT patients. We assessed these patients based on their clinical presentation and using an anti-PF4 IgG ELISA and a functional PF4-dependent platelet activation assay. Results: We found that when the 283 clinically suspected VITT patients were analysed in the anti-PF4 IgG ELISA: 24 (8.5%) tested positive, 248 (87.6%) tested negative, and 11 (3.9%) tested weak positive. Out of the 24 patients that tested positive in the anti-PF4 IgG ELISA, 19 (79.2%) patients also demonstrated increased PF4-dependent platelet activation. Furthermore, we observed that platelet activation was inhibited by excess levels of heparin and by a FcγRIIa-blocking antibody, indicating a role for platelet-FcγRIIa in the pathophysiology of VITT. Remarkably, we found that patients vaccinated with mRNA vaccines BTN162b2 (N = 84) and mRNA-1273 (N = 36), did not test positive in the anti-PF4 IgG ELISA. Based on these test results 19 patients (11 women) were eventually diagnosed with probable VITT, of which 13 presented with both thrombocytopenia and thrombosis and three suffered from CVST. Strikingly, discrepancies in test results were also present, including nine patients with low levels of anti-PF4 IgG but with increased PF4-dependent platelet activation, and two patients with high levels of anti-PF4 IgG but without any PF4-dependent platelet activation. Summary/Conclusions: VITT is a rare but serious complication of SARS-CoV-2 virus vaccination, particularly due to adenovirus vectorbased vaccines. Our results underline the importance of using the clinical presentation, in combination with the anti-PF4 IgG ELISA and the PF4-dependent platelet activation assay for VITT diagnostics. Discrepancies in test results, however, proved it difficult to unequivocally diagnose VITT. Therefore, it will be essential to obtain more insights into the pathophysiology of VITT in order to improve the diagnostic accuracy and identify preventive and therapeutic approaches.
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Background: Trials on convalescent plasma (CP) for hospitalized patients with COVID-19 have not demonstrated clear benefits. However, data on outpatients with early symptoms are limited. We studied if treatment with CP reduces disease burden of outpatients treated in the first 7 days of symptoms. Methods: Two double blind randomized trials (NCT04621123, NCT04589949) were merged. Pooling of data started when <20% of their predefined sample size had been recruited. A Bayesian adaptive individual patient data meta-analysis was implemented. Analyses were done with Bayesian proportional odds and logistic models, where odds ratios(OR)<1.0 indicate a favorable outcome for CP. A DSMB monitored the accumulating data for efficacy. Patients aged ≥50, diagnosed with COVID-19 and symptomatic for ≤7days were eligible for participation. The intervention was one unit (200-300mL) of CP with a predefined minimum level of antibodies. The two primary endpoints were (a) a 5-point disease severity scale (fully recovered by day 7 or not, hospital or ICU admission and death) and (b) a composite of hospitalization or death. Secondary endpoints were efficacy in patients with ≤5days of symptoms and time to full symptom resolution. Results: Of 797 patients included, 390 received CP and 392 placebo. They had a median age of 58, 1 comorbidity, symptoms for 5 days and 93% tested negative for SARS-CoV-2 S-protein IgG antibodies. 74 patients were hospitalized, 6 required mechanical ventilation and 3 died. The OR of CP for an improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311). The OR for hospitalization or death was 0.919 (CI 0.592-1.416). The effect of CP on hospital admission or death was largest in patients with ≤5days of symptoms (OR 0.658, 95% CI 0.394-1.085). CP did not decrease the time to full symptom resolution (p=0.62). Conclusion: Treatment with CP of outpatients in the first 7 days of symptoms did not improve outcome of COVID-19. The possible beneficial effect in patients with ≤5days of symptoms requires further study.
ABSTRACT
Background: Optimising red cell transfusion requires an understanding of both the risks and the benefits. Adverse events of red cell transfusions, like transfusion reactions and iron overload are reasons for considering a restrictive transfusion strategy. However, there are no completed trials in the outpatient setting for chronic transfusion-dependent patients, and little data in general about the value of outpatient transfusions. With no objective parameters to measure the benefits of red cell transfusions, a restrictive transfusion strategy may not be optimal for patients who require RBCT on a regular basis. Transfusions are ordered primarily based on haemoglobin concentrations and a subjective interpretation of symptoms of anaemia. Endpoints that may be more clinically relevant include quality of life measurements, vital signs, functional activity and cognition. To date, there has been little systematic assessment of tools that assess these measures and no published trials that have examined the impact of transfusions on functional outcomes in transfusion-dependent patients. Aims: The aim of this study is to understand how wearable devices and web-based testing can be used to measure physiological changes and functional activity in a cohort of transfusion-dependent patients. Methods: We monitored 5 patients who chronically receive transfusions during one transfusion cycle with the VitalPatch. and Withings Steel HR. Patients completed CANTAB cognitive tasks, QUALMS and PROMIS quality of life questionnaires through web-based testing. Outcomes were first the quality and usability of data. Second, we leveraged mixed models to evaluate transfusion-induced changes in 1) heart rate, 2) activity, 3) sustained attention, and 4) patient-reported quality of life. Results: Captured data was 97,8% high quality and usable for the VitalPatch;98,9% for the Withings Steel HR. The sent out web-based CANTAB tasks and questionnaires were all completed on the appointed days. Heart rate and sustained attention are significantly and reversibly affected by RBC transfusions, corrected for predefined confounders (Fig. 1): Mean daytime heart rate was 76.5±2.8 bpm before and 72.3±2.8 after transfusion (P=0.002). Sustained attention (RVPA) increased from 8586±140 to 9141±183 after transfusion (P=0.004). Activity and quality of life measures did not yield transfusion-induced changes. The measured activity data may not be representative as the study was conducted during the COVID-19 induced lockdown.