Irinotecan-Induced Toxicity:A Pharmacogenetic Study Beyond UGT1A1

Background and objective: Side effects of irinotecan treatment can be dose limiting and may impair quality of life. In this study, we investigated the correlation between single nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in the irinotecan metabolism and transport, outside UGT1A1, and irinotecan-related toxicity. We focused on carboxylesterases, which are involved in formation of the active metabolite SN-38 and on drug transporters. Methods: Patients who provided written informed consent at the Erasmus Medical Center Cancer Institute to the Code Geno study (local protocol: MEC02-1002) or the IRI28-study (NTR-6612) were enrolled in the study and were genotyped for 15 SNPs in the genes CES1, CES2, SLCO1B1, ABCB1, ABCC2, and ABCG2. Results: From 299 evaluable patients, 86 patients (28.8%) developed severe irinotecan-related toxicity. A significantly higher risk of toxicity was seen in ABCG2 c.421C&gt;A variant allele carriers (P = 0.030, OR 1.88, 95% CI 1.06–3.34). Higher age was associated with all grade diarrhea (P = 0.041, OR 1.03, 95% CI 1.00–1.06). In addition, CES1 c.1165-41C&gt;T and CES1 n.95346T&gt;C variant allele carriers had a lower risk of all-grade thrombocytopenia (P = 0.024, OR 0.42, 95% CI 0.20–0.90 and P = 0.018, OR 0.23, 95% CI 0.08–0.79, respectively). Conclusion: Our study indicates that ABCG2 and CES1 SNPs might be used as predictive markers for irinotecan-induced toxicity.</p

Life-prolonging treatment restrictions and outcomes in patients with cancer and COVID-19:an update from the Dutch Oncology COVID-19 Consortium

AIM OF THE STUDY: The coronavirus disease 2019 (COVID-19) pandemic significantly impacted cancer care. In this study, clinical patient characteristics related to COVID-19 outcomes and advanced care planning, in terms of non-oncological treatment restrictions (e.g. do-not-resuscitate codes), were studied in patients with cancer and COVID-19. METHODS: The Dutch Oncology COVID-19 Consortium registry was launched in March 2020 in 45 hospitals in the Netherlands, primarily to identify risk factors of a severe COVID-19 outcome in patients with cancer. Here, an updated analysis of the registry was performed, and treatment restrictions (e.g. do-not-intubate codes) were studied in relation to COVID-19 outcomes in patients with cancer. Oncological treatment restrictions were not taken into account. RESULTS: Between 27th March 2020 and 4th February 2021, 1360 patients with cancer and COVID-19 were registered. Follow-up data of 830 patients could be validated for this analysis. Overall, 230 of 830 (27.7%) patients died of COVID-19, and 60% of the remaining 600 patients with resolved COVID-19 were admitted to the hospital. Patients with haematological malignancies or lung cancer had a higher risk of a fatal outcome than other solid tumours. No correlation between anticancer therapies and the risk of a fatal COVID-19 outcome was found. In terms of end-of-life communication, 50% of all patients had restrictions regarding life-prolonging treatment (e.g. do-not-intubate codes). Most identified patients with treatment restrictions had risk factors associated with fatal COVID-19 outcome. CONCLUSION: There was no evidence of a negative impact of anticancer therapies on COVID-19 outcomes. Timely end-of-life communication as part of advanced care planning could save patients from prolonged suffering and decrease burden in intensive care units. Early discussion of treatment restrictions should therefore be part of routine oncological care, especially during the COVID-19 pandemic

Exploring, Diversifying and Debating Sustainable Health (Care) Approaches

Today’s sustainability challenges have major implications for human health and health care. At the same time, the way health care is organized and conducted has major sustainability implications. Sustainable health and sustainable health care approaches in research, which engage with health and sustainability as intertwined phenomena, feature increasingly prominently in various literatures, i.e. (i) literature based on the premise of ‘(un)healthy environments result in (un)healthy people’ (e.g., planetary health); (ii) literature on the implications of ecological change for the sustainability of healthcare systems; and (iii) literature on healthcare systems’ sustainability in view of a range of socio‐economic factors. However, an integrative elaboration of the manifold relationships between health and sustainability challenges in these literatures is currently lacking. This review paper therefore maps how these three literatures represent intertwinements between health and sustainability challenges, as well as their suggestions to address these challenges. In addition, we explore which themes and questions are pertinent, meaning they have remained largely unaddressed. By performing a qualitative mapping review, we find that calls for structural attention to inequality, to in‐and exclusion, and to stakeholder needs and perspectives cut across these three literatures. Furthermore, we identify three cross‐cutting key questions that require future research attention. First, how do divergent ideas on what is and divergent ideas on how can that be known give rise to different health‐ and sustainability visions and pathways? Second, what do abstract problem statements and solutions presented in agenda‐setting work look like in practice in specific and diverse empirical contexts across the globe? And third, how are diverse health and sustainability dynamics historically and spatially interconnected? Moreover, we observe that some voices have so far remained largely silent in scientific debates on health and sustainability intertwinements, namely non‐expert voices such as patients and citizens, voices from a variety of social scientific and humanities disciplines, voices from relevant domains beyond (environmental) health, and voices from the global South (from non‐experts, social scientific and humanities researchers and domains beyond health). We conclude that a focus on inclusive and equitable engagement with intertwined health‐ and sustainability challenges is imperative. This requires moving away from developing universal knowledge to address generic problems, to foregrounding plurality in terms of problem statements, knowledge, solutions, and the values embedded therein

Movement behaviour patterns in patients with hip and/or knee osteoarthritis in the physical therapy setting: a cross-sectional study

Background: Osteoarthritis is one of the most common chronic joint diseases, mostly affecting the knee or hip through pain, joint stiffness and decreased physical functioning in daily life. Regular physical activity (PA) can help preserve and improve physical functioning and reduce pain in patients with osteoarthritis. Interventions aiming to improve movement behaviour can be optimized by tailoring them to a patients' starting point; their current movement behaviour. Movement behaviour needs to be assessed in its full complexity, and therefore a multidimensional description is needed. Objectives: The aim of this study was to identify subgroups based on movement behaviour patterns in patients with hip and/or knee osteoarthritis who are eligible for a PA intervention. Second, differences between subgroups regarding Body Mass Index, sex, age, physical functioning, comorbidities, fatigue and pain were determined between subgroups. Methods: Baseline data of the clinical trial 'e-Exercise Osteoarthritis', collected in Dutch primary care physical therapy practices were analysed. Movement behaviour was assessed with ActiGraph GT3X and GT3X+ accelerometers. Groups with similar patterns were identified using a hierarchical cluster analysis, including six clustering variables indicating total time in and distribution of PA and sedentary behaviours. Differences in clinical characteristics between groups were assessed via Kruskall Wallis and Chi2 tests. Results: Accelerometer data, including all daily activities during 3 to 5 subsequent days, of 182 patients (average age 63 years) with hip and/or knee osteoarthritis were analysed. Four patterns were identified: inactive & sedentary, prolonged sedentary, light active and active. Physical functioning was less impaired in the group with the active pattern compared to the inactive & sedentary pattern. The group with the prolonged sedentary pattern experienced lower levels of pain and fatigue and higher levels of physical functioning compared to the light active and compared to the inactive & sedentary. Conclusions: Four subgroups with substantially different movement behaviour patterns and clinical characteristics can be identified in patients with osteoarthritis of the hip and/or knee. Knowledge about these subgroups can be used to personalize future movement behaviour interventions for this population

Fysiek fit de operatie in

Een grote oncologische operatie is een ingrijpende gebeurtenis. Voor het lichaam is het een zware inspanning die wordt vergeleken met het lopen van een marathon waarbij dezelfde fysiologische reacties optreden. Met deze vergelijking voor ogen is het vreemd dat patiënten zich op een operatie anders voorbereiden dan sporters op een marathon.Uit de praktijk blijkt dat patiënten in de periode voor de operatie lichamelijk minder actief worden. Dit vanuit de verkeerde gedachte dat rust een goede voorbereiding is op wat hen te wachten staat. Familie en vrienden, maar ook zorgverleners, dragen vaak, vanuit een goed bedoelde bezorgdheid, volop bij aan deze gedachte. Patiënten en zorgverleners kunnen hierin leren van sporters. Patiënten die de operatie met een goede fysieke fitheid ingaan, herstellen daarna beter dan patiënten waarbij de fitheid te wensen overlaat. Niet-fitte patiënten hebben een hoger risico op het krijgen van complicaties en ervaren na de operatie veelal een langdurige of blijvende afname van de fysieke fithei

Governing translocal experimentation in multi-sited transition programs: Dynamics and challenges

Transition experiments are important instruments to foster sustainability transitions. Transition scholars increasingly suggest investigating how multiple local experiments can become connected across spatial scales, and how transformative dynamics of multiple connected experiments can be facilitated and governed. In this paper we analyze the different types of translocal dynamics involved in simultaneously governing multiple experiments in multi-sited transition programs, by empirically exploring the FIT4FOOD2030 program (2017-2020) that supported 25 transition experiments. Then, we present four overarching challenges in governing translocal experimentation: (1) finding synergies between diverging local needs and program ambitions; (2) navigating the cross-scale political dynamics in multi-sited transition programs; (3) moving beyond output-oriented evaluation frameworks in order to capture transformative efforts of short-term programs; and (4) expanding the boundaries of programs by linking to ongoing policy developments in highly complex multi-level governance settings. We hope our work can inform transition governance efforts in fostering transformative translocal dynamics toward sustainability