A Prediction Model for Successful Increase of Adalimumab Dose Intervals in Patients with Crohn’s Disease:Secondary Analysis of the Pragmatic Open-Label Randomised Controlled Non-inferiority LADI Trial

Background: In the pragmatic open-label randomised controlled non-inferiority LADI trial we showed that increasing adalimumab (ADA) dose intervals was non-inferior to conventional dosing for persistent flares in patients with Crohn’s disease (CD) in clinical and biochemical remission. Aims: To develop a prediction model to identify patients who can successfully increase their ADA dose interval based on secondary analysis of trial data. Methods: Patients in the intervention group of the LADI trial increased ADA intervals to 3 and then to 4 weeks. The dose interval increase was defined as successful when patients had no persistent flare (&gt; 8 weeks), no intervention-related severe adverse events, no rescue medication use during the study, and were on an increased dose interval while in clinical and biochemical remission at week 48. Prediction models were based on logistic regression with relaxed LASSO. Models were internally validated using bootstrap optimism correction. Results: We included 109 patients, of which 60.6% successfully increased their dose interval. Patients that were active smokers (odds ratio [OR] 0.90), had previous CD-related intra-abdominal surgeries (OR 0.85), proximal small bowel disease (OR 0.92), an increased Harvey-Bradshaw Index (OR 0.99) or increased faecal calprotectin (OR 0.997) were less likely to successfully increase their dose interval. The model had fair discriminative ability (AUC = 0.63) and net benefit analysis showed that the model could be used to select patients who could increase their dose interval. Conclusion: The final prediction model seems promising to select patients who could successfully increase their ADA dose interval. The model should be validated externally before it may be applied in clinical practice. Clinical Trial Registration Number: ClinicalTrials.gov, number NCT03172377.</p

Aansluiting middelbaar agrarisch onderwijs en arbeidsmarkt 1990 [Connection between secondary agricultural education and labour market 1990]

Two cohorts of students finished their secondary agricultural education (MAO) in the years 1978 and 1987 were traced and they were asked to evaluate their education and their career. Agricultural background / preliminary training / residence of MAO / subject / importance of fields of study in present job / attention paid to fields of study and practical skills during MAO / daytime education and courses after MAO of importance for career / need for courses and training at the moment / informed about courses and training of the MAO / has planned to follow courses in the near future, and motivation / description of present function and additional functions: activities, independence, had enough education to do job well, hierarchical level, education of leader, number of employees of company, expectations of employment in future for company, preference for full-time or part-time job, ( not ) satisfied with aspects of job ( level, promotion, work load, circumstances, scope to develop, working hours, income ), how did respondent get present job / has been unemployed involuntary after MAO / description of functions after MAO, before present function / most important cause of not having a paid job / social benefit / chances for paid job in near future / self-employed entrepreneurship / informed about vacancies / time spending on housekeeping and voluntary work / expectations about future of agriculture Background variables: basic characteristics/ household characteristics/ occupation/employment/ income/capital assets/ education/ readership, mass media, and 'cultural' exposur

Participerend leren onder de loupe.

Beschrijving van een nieuw onderzoeksproject waarin de didactiek van het vernieuwde voortgezet agrarisch onderwijs wordt onderzoch

Past human-landscape interactions in the Netherlands: Reconstructions from sand belt to coastal-delta plain for the first millennium AD

The first millennium AD represents a transition period in the Netherlands from a mainly natural prehistorical lowland landscape to a landscape that was increasingly influenced by humans. This thesis focuses on human-landscape interactions in the coastal plain, the delta, and the Pleistocene sand area during this time interval. Geomorphological changes were identified using new reconstruction maps, and their causes and effects were assessed and compared to archaeological records following an integrative approach. Already in the first millennium AD, human activities caused major unintended geomorphological changes in all studied landscapes. In the coastal plain, intensified agricultural use of artificially-drained peatlands since the Late Iron Age (250–12 BC) led to soil subsidence, on a large scale turning peatland into tidal areas that for many centuries would remain unsuitable for habitation. Ingressive tidal systems reached furthest inland where the peaty back-barrier was widest, whereas sea-ingression formation was hampered in areas with abundant beach-barriers and supratidal levees protecting the coast from drowning. Human-induced peatland subsidence also led to a major reorganization of the river network in the lower delta: it caused the formation of the new Hollandse IJssel and Lek river branches, which now invaded the extensive peatlands. In the Rhine-Meuse delta, natural levees were important elements in the landscape. Especially new generations of natural levees, which developed during the first millennium AD, were positioned 0.5 to 1.0 m higher than preceding levee generations. This is attributed to an increase in suspended sediment supply caused by deforestation of the hinterland, as well as by increased flooding intensity during their formation. The increased flooding frequency in the first millennium AD also caused settlements on the natural levees to shift towards higher locations within the river area. In areas where new large river branches developed (around the Waal) this effect was strongest. Despite the dynamic of the landscape, no large-scale settlement abandonment occurred and route networks between settlements remained largely intact. In the Pleistocene sand area, sand drifting occurred on a relatively small scale. This phenomenon, most frequently occurring close to human movement corridors, increased after ca. AD 900, coeval with rising population density and large-scale deforestation. This implies that sand drifting was strongly related to human pressure on the landscape. Reclamation and overexploitation led to unintended loss of land, because it became more prone to storms and floods. This study provides more insights in the circumstances under which impact of human action on the landscape was largest. This impact forced humans to adapt or to abandon the area in case the new situation could not be coped with. Better understanding of human impact on the natural landscape in the past is especially relevant to better cope with threats from floods or sea-level rise, especially in densely populated and subsiding deltas

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