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01 juli 2023, Item does not contain fulltext, BACKGROUND AND OBJECTIVE: Underdosing of adalimumab can result in non-response and poor disease control in patients with rheumatic disease or inflammatory bowel disease. In this pilot study we aimed to predict adalimumab concentrations with population pharmacokinetic model-based Bayesian forecasting early in therapy. METHODS: Adalimumab pharmacokinetic models were identified with a literature search. A fit-for-purpose evaluation of the model was performed for rheumatologic and inflammatory bowel disease (IBD) patients with adalimumab peak (first dose) and trough samples (first and seventh dose) obtained by a volumetric absorptive microsampling technique. Steady state adalimumab concentrations were predicted after the first adalimumab administration. Predictive performance was calculated with mean prediction error (MPE) and normalised root mean square error (RMSE). RESULTS: Thirty-six patients (22 rheumatologic and 14 IBD) were analysed in our study. After stratification for absence of anti-adalimumab antibodies, the calculated MPE was -2.6% and normalised RMSE 24.0%. Concordance between predicted and measured adalimumab serum concentrations falling within or outside the therapeutic window was 75%. Three patients (8.3%) developed detectable concentrations of anti-adalimumab antibodies. CONCLUSION: This prospective study demonstrates that adalimumab concentrations at steady state can be predicted from early samples during the induction phase. CLINICAL TRIAL REGISTRATION: The trial was registered in the Netherlands Trial Register with trial registry number NTR 7692 ( www.trialregister.nl ).

Introduction: To calculate the maternal mortality ratio (MMR) for 2006–2018 in the Netherlands and compare this with 1993–2005, and to describe women’s characteristics, causes of death and improvable factors. Material and Methods: We performed a nationwide, cohort study of all maternal deaths between January 1, 2006 and December 31, 2018 reported to the Audit Committee Maternal Mortality and Morbidity. Main outcome measures were the national MMR and causes of death. Results: Overall MMR was 6.2 per 100 000 live births, a decrease from 12.1 in 1993–2005 (risk ratio [RR] 0.5). Women with a non-western ethnic background had an increased MMR compared with Dutch women (MMR 6.5 vs. 5.0, RR 1.3). The MMR was increased among women with a background from Surinam/Dutch Antilles (MMR 14.7, RR 2.9). Half of all women had an uncomplicated medical history (79/161, 49.1%). Of 171 pregnancy-related deaths within 1 year postpartum, 102 (60%) had a direct and 69 (40%) an indirect cause of death. Leading causes within 42 days postpartum were cardiac disease (n = 21, 14.9%), hypertensive disorders (n = 20, 14.2%) and thrombosis (n = 19, 13.5%). Up to 1 year postpartum, the most common cause of death was cardiac disease (n = 32, 18.7%). Improvable care factors were identified in 76 (47.5%) of all deaths. Conclusions: Maternal mortality halved in 2006–2018 compared with 1993–2005. Cardiac disease became the main cause. In almost half of all deaths, improvable factors were identified and women with a background from Surinam/Dutch Antilles had a threefold increased risk of death compared with Dutch women without a background of migration.

Objective: The International Consortium for Health Outcomes Measurement developed the Pregnancy and Childbirth (PCB) outcome set to improve value-based perinatal care. This set contains clinician-reported outcomes and patient-reported outcomes. We validated the set for use in the Netherlands by exploring its applicability among all end-users prior to implementation. Methods: A mixed-methods design was applied. A survey was performed to assess patients (n = 142), professionals (n = 134) and administrators (n = 35) views on the PCB set. To further explore applicability, separate focus groups were held with representatives of each of these groups. Results: The majority of survey participants agreed that the PCB set contains the most important outcomes. Patient-reported experience measures were considered relevant by the majority of participants. Perceived relevance of patient-reported outcome measures varied. Main themes from the focus groups were content of the set, data collection timing, implementation (also IT and transparency), and quality-based governance. Conclusion: This study supports suitability of the PCB outcome set for implementation, evaluation of quality of care and shared decision making in perinatal care. Practice Implications: Implementation of the PCB set may change existing care pathways of perinatal care. Focus on transparency of outcomes is required in order to achieve quality-based governance with proper IT solutions.

Objective: Develop a core outcome set of international consensus definitions for severe maternal morbidities. Design: Electronic Delphi study. Setting: International. Population: Eight expert panels. Methods: All 13 high-income countries represented in the International Network of Obstetric Surveillance Systems (INOSS) nominated five experts per condition of morbidity, who submitted possible definitions. From these suggestions, a steering committee distilled critical components: eclampsia: 23, amniotic fluid embolism: 15, pregnancy-related hysterectomy: 11, severe primary postpartum haemorrhage: 19, uterine rupture: 20, abnormally invasive placentation: 12, spontaneous haemoperitoneum in pregnancy: 16, and cardiac arrest in pregnancy: 10. These components were assessed by the expert panel using a 5-point Likert scale, following which a framework for an encompassing definition was constructed. Possible definitions were evaluated in rounds until a rate of agreement of more than 70% was reached. Expert commentaries were used in each round to improve definitions. Main outcome measures: Definitions with a rate of agreement of more than 70%. Results: The invitation to participate in one or more of eight Delphi processes was accepted by 103 experts from 13 high-income countries. Consensus definitions were developed for all of the conditions. Conclusion: Consensus definitions for eight morbidity conditions were successfully developed using the Delphi process. These should be used in national registrations and international studies, and should be taken up by the Core Outcomes in Women's and Newborn Health initiative. Tweetable abstract: Consensus definitions for eight morbidity conditions were successfully developed using the Delphi process.

Parkinson’s disease (PD) is one of the most common neurological diseases in adults over the age of 65. Current monitoring of disease stage and progression consists of physician visits, which is inefficient and unreliable since symptom severity varies throughout the day. A more practical solution could include monitoring behavior throughout the day. Previous work has found that typing behavior is an accurate way to differentiate people with PD from those without PD. This finding leads to the idea that it may also be useful to use keyboard characteristics to detect PD severity. The current study examined whether this was possible. Additionally, it compared three different machine learning methods: logistic regression, k¬-nearest neighbors, and random forests. Finally, it examined how accuracy of the classification of PD severity differed when including increasing amounts of keystrokes (1000, 2000, and 5000 keystrokes). It was found that the random forests classifier could predict PD stage moderately well in the 5000-keystroke dataset. However, there was no further difference in model type or clear pattern to show that models become more accurate with increased amounts of keystrokes. This study is a first step in examining how computer behaviors might be able to be used for predicting and potentially monitoring PD patients’ disease stage.

In this master thesis the flow behavior and the performance of a bow tunnel thruster at slow forward vessel motion is studied using Computational Fluid Dynamics (CFD). The study analyzes the flow and the turning ability for a cylindrical cross-section and the effect of changing the cross-section of the bow tunnel thruster. At Royal IHC it is noticed that trailing suction hopper dredgers experience a significant decrease in turning ability, using the bow tunnel thrusters, when trailing at a speed through the water of 5 [kts] in comparison to zero forward speed. Dredgers are often operating at those speeds, use the bow tunnel thruster to keep course and therefore often experience this effect in practice. To study the flow behavior the commercial CFD solver Numeca FineMarine is used. Computations are made on model scale using a simplified wedge model of a container ship (Nienhuis wedge) for validation purpose and of a trailing suction hopper dredger (Hopper wedge). For the Nienhuis wedge multiple numerical studies are performed that focus on the used set-up, non-linear iterations and convergence, time step, actuator disk modeling and first layer thickness. A grid study together with a verification and validation study close the analysis of the Nienhuis wedge. The settings from the Nienhuis wedge are used for the computations with the Hopper wedge. For the Hopper wedge a systematic tunnel cross-section variation is derived and three different shapes are computed at different ship speeds: a circular cross-section (S1010A), flattened cross-section (S0610A) and a streamlined cross-section (S0602A). The flow of the tunnel jet and the flow around the ship are comparable to the flow of a jet in a cross-flow. The flow is unsteady and fluctuates. Once the tunnel jet flow leaves the tunnel the flow interacts with the surrounding flow and is bend into the direction of that surrounding flow. A large wake region is visible behind the jet. The velocity ratio $m$ between the ship spe, Marine Technology - Track Science - Specialization Ship Hydromechanics (MT-SC-SH), Maritime and Transport Technology (M&TT), Mechanical, Maritime and Materials Engineering

Background The Dutch maritime industry has only limited knowledge about Arctic engineering, in spite of a growing market and interest by the oil and gas industry. This literature survey is the first in a series of three reports to develop a concept design of an Arctic Offshore Support Vessel (AOSV). The purpose is to give a perspective on Arctic shipping with a specific focus on offshore platform support and to provide a design framework for AOSVs. The information in this report is based on technical papers from the Internet, contact with different companies and Arctic courses from the Aalto University in Espoo, Finland. Results In general oil companies have a rising interest in the natural resource in the Arctic region. Next to their spending in Research and Development (R&D), also shipyards, suppliers and operators are eager to increase development for the harsh environments. This study shows, that every region in the Arctic has different weather and infrastructure conditions as well as different national laws and regulations. Next to that, operations in the harsh environment have high impact on the performance of the ship and its crew. This report gives an overview on technology available for operating in the Arctic, such as double acting hull, azimuth thrusting and other ice breaking technologies. Increasing research in Arctic engineering results in new, more reliable technologies and opens the possibility to design more advanced Arctic vessels. A big challenge in Arctic engineering is to have a optimal compromise between open water and ice behavior. Due to higher costs for among others R&D, material and equipment an AOSV will be more expensive. Operators, on the other hand, are also willing to pay more for them, because of the high amount of natural resources in the Arctic region. The expected focus of the industry is on Baffin Bay, Barents Sea and Beaufort Sea. This study discusses the estimated oil reserves, existing infrastructure and environmental impact. A, Marine & Transport Technology, Mechanical, Maritime and Materials Engineering

Background To design a ship its specific design requirements are to be known. These are, together with class notations, specified in previous reports and extended in this report. Since the requirements are formed iteratively, design freedom is possible. This is used to implement several innovations into the design which improve the performance of the vessel. The vessel is designed for worldwide operations to support offshore installations, in open waters and first year ice. Results The vessel is built with regards to a good performance in open water and ice, safe transportation of cargo and safe working conditions for the crew. The hull of the ship is designed with three operational modes in mind. An open water bow for low resistance in open water, an ice bow to allow good performance in ice and both are designed to reduce slamming during dynamic positioning operations. Installation of two Azipod thrusters gives good maneuverability with little compromise on performance in ice or open water. Four engines with three different sizes make sure the power supply meets the requirement, minimizing energy losses due to overcapacity. To meet strict environmental laws the ship is able to use LNG as fuel and therefore does not exhaust SOx. Besides that fuel oil can be used in less strict areas. The hold is filled with tanks for dry bulk and liquid mud, meeting the average for this size of vessel. Winterization is achieved by the extended superstructure (ESS) which protects crew, cargo and even survivors from an oil rig catastrophe from the environment. As the market changes, the demands for ships change. The modular container hold allows for extra tanks, pumps and engines to be placed, adapting the ship to owner needs. Even towing is possible, and might even be necessary when performing ice management. There are however some design choices that require attention. The ESS, in combination with the LNG tanks, limits the line of sight from the bridge. Helicopter landing facilities, Martitime Technology, Mechanical, Maritime and Materials Engineering

Background At the start of a design it is often good to look at comparable designs. What choices were made, what are the operations, what equipment is used? This report looks at three Damen ships, which are already capable of offshore support. These vessels are designed for open water. Looking just at what has to improve for operating in the Arctic will give a feeling for the design of such vessels. The recommendations are taken into account in the next report, where a concept design of an Arctic Offshore Support Vessel will be developed. Results There are two operational profiles per vessel. One is the original operational profile and the other one is about the same operations but then in ice. The operational profiles are used for calculating an indication of fuel consumption. The ships themselves are tested on winterization, resistance, propulsion, construction and stability. This is done according to rules and guidelines available. For the resistance prediction the Lindqvist and Riska formulae are used. Winterization of the ships is very well possible, because the superstructure that is in place is already providing cover. The working and safety areas that are still outside have to be enclosed and the equipment that is on deck will have to be winterized. The resistance of the ships can only be determined with Riska, due to the fact that the bow angles are not intended for icebreaking. This results in a negative crushing component with Lindqvist. A high resistance is the result for the three vessels, leading to a high required propulsion power, around 30 MW. This is rather high compared to similar vessel, Vitus Bering, which requires 13 MW for the same speed and ice thickness. Sailing backwards through the ice could be an option to decrease this power requirement. There are relatively minor adaptions required to do so. Looking at the construction, a ice strengthening has to be applied to the hull. Dependent on the class notation and location around the hull, the s, Marine & Transport Technology, Mechanical, Maritime and Materials Engineering