Citations

There is an evolving landscape of systemic combination regimens for patients with advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In this review, we provide a comprehensive outline of the existing clinical trials/prospective studies investigating these combinations. PubMed was searched using key relevant terms to identify articles referring to GEP-NETs and combination treatments. No systematic search of the literature or metanalysis of the data was performed, and we focused on the most recent literature results. Primarily, phase 1 and 2 clinical trials were available, with a smaller number of phase 3 trials, reporting results from combination treatments across a wide range of antiproliferative agents. We identified significant variability in the anti-tumor activity of the reported combinations, with occasional promising results, but only a very small number of practice-changing phase 3 clinical trials. Overall, the peptide receptor radionuclide therapy (PRRT)-based combinations (with chemotherapy, dual PPRT, and targeted agents) and anti-vascular endothelial growth factor (VEGF) agent combinations with standard chemotherapy were found to have favorable results and may be worth investigating in future, larger-scale trials. In contrast, the immune-checkpoint inhibitor-based combinations were found to have limited applicability in advanced, well-differentiated GEP-NETs.

AbstractINTRODUCTIONWe examined associations between plasma‐derived biomarkers of Alzheimer's disease (AD) and neuropsychiatric symptoms (NPS) in community‐dwelling older adults.METHODSCross‐sectional study involving 1005 persons ≥50 years of age (mean 74 years, 564 male, 118 cognitively impaired), who completed plasma‐derived biomarker (amyloid beta 42 [Aβ42]/Aβ40, phosphorylated tau 181 [p‐tau181], p‐tau217, total tau [t‐tau], neurofilament light [NfL]), and NPS assessment.RESULTSP‐tau181 (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.41–3.00, p < 0.001), p‐tau217 (OR 1.70, 95% CI 1.10–2.61, p = 0.016), and t‐tau (OR 1.44, 95% CI 1.08–1.92, p = 0.012) were associated with appetite change. We also found that p‐tau181 and p‐tau217 were associated with increased symptoms of agitation (OR 1.93, 95% CI 1.20–3.11, p = 0.007 and OR 2.04, 95% CI 1.21–3.42, p = 0.007, respectively), and disinhibition (OR 2.39, 95% CI 1.45–3.93, p = 0.001 and OR 2.30, 95% CI 1.33–3.98, p = 0.003, respectively). Aβ42/Aβ40 and NfL were not associated with NPS.CONCLUSIONHigher plasma‐derived p‐tau181 and p‐tau217 levels are associated with increased symptoms of appetite change, agitation, and disinhibition. These findings may support the validity of plasma tau biomarkers for predicting behavioral symptoms that often accompany cognitive impairment.HIGHLIGHTS We studied 1005 community‐dwelling persons aged ≥ 50 years Higher plasma tau levels are associated with increased neuropsychiatric symptoms Aβ42/Aβ40 and NfL are not associated with neuropsychiatric symptoms Clinicians should treat neuropsychiatric symptoms in persons with high plasma‐derived tau

Abstract Background Experiencing clinical catastrophes can result in long‐lasting emotional and psychological impacts. In other fields, crisis simulation has been used to train professionals in coping skills. Approach Our workshop combined a simulated case with a clinical debrief and expert‐led teaching on coping skills. The ‘4Rs’ mnemonic, Recognise, Reflect, Reframe and Reach‐out, describes the key elements. This is grounded in social, cognitive and behavioural theories of stress and coping. Evaluation All 96 anesthesiology residents from one residency programme participated, in small groups, and a mixed methods analysis was used. The scenario was deemed stressful. The workshop introduced new techniques, with 72/87 (82.75%) reporting new coping skills in use at 1‐month follow‐up. For many residents, the descriptive language regarding their performance and abilities shifted from critical, negative self‐talk to positive and team‐focused immediately following the workshop. A striking finding from evaluations at all timepoints was that negative comments were typically self‐referencing whereas positive ones referenced colleague support and the team. Implications Combining stress exposure with formal exploration of emotional responses and coping skills teaching in this workshop was feasible, with benefits at 1‐month follow‐up. This laid the groundwork for a resilience curriculum and wider departmental interest in the topic of coping and stress responses.