21 1 Inclinical settings, physicians andnurse specialists continue tounderdiagnosedelirium[83]. Assessmenttoolsforclinicianswithoutpsychiatrictrainingtoidentifyandrecognizedelirium. are helpful. Although there are a plethora of validated delirium screening tools, it is unclear which tool best suits particular populations [84]. The ideal screening tool should have a high level of sensitivity, be brief and easy to use with minimal training [85]. The nurse-based Delirium Observation Screening (DOS) Scale is a brief screening tool based on observation [86]. The DOS has been validated in several patient populations, but no published studies focused on an inpatient population with advanced cancer. In chapter 6 we compare the accuracy of the DOS as a screening tool for delirium in patients with advanced cancer with the clinician-based Delirium Rating Scale-revised-98 (DRS-R98) tool [87] in a prospective study. Delirium treatment in patients with advanced cancer is complex, as it involves addressing multiple domains [88]. Although it is now recognised that there are multiple factors implicated in the aetiology of delirium [89, 90], there are likely several neurobiological processes that contribute to delirium pathogenesis, including neuroinflammation, brain vascular dysfunction, altered brainmetabolism, neurotransmitter imbalance and impaired neuronal network connectivity (Figure 4). The cerebral imbalance resulting in a relative excess of dopaminergic and deficiency of cholinergic transmission has been one of the main proposed mechanisms in the neuropathogenesis of delirium [91]. It has also provided a target mechanism or basis for much of the strategic approach in the pharmacological management of delirium with antipsychotics used historically in delirium treatment [92]. Typical antipsychotic drugs (e.g. haloperidol) act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors [93]. Owing to this D2 blockade, they also induce a number of side effects, among which extrapyramidal symptoms are the most prominent. Atypical antipsychotics (e.g. olanzapine) have lower affinity and occupancy for the dopaminergic receptors and a high degree of occupancy of the serotoninergic receptors 5-HT2A [94]. Compared to typical antipsychotics, atypicals are supposed to induce fewer extrapyramidal side effects. [95]. In Chapter 7, the results of a multicenter, randomized, phase III study to compare the efficacy and tolerability of olanzapine with haloperidol for the treatment of delirium in a population of hospitalized patients with advanced cancer are described. Summarizing discussion and future perspectives In chapter 8 the main findings in this thesis are summarized and discussed. Finally, recommendations for future research are presented. A Dutch summary of this thesis is given in the Appendices, that also hold a list of publications, acknowledgements, and a curriculum vitae of the PhD candidate.
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