Patients, family members and providers perceive family-administered delirium detection tools in the adult ICU as feasible and of value to patient care and family member coping: a qualitative focus group study.

PURPOSE: While studies report on perceptions of family participation in delirium prevention, little is known about the use of family-administered delirium detection tools in the care of critically ill patients. This study sought the perspectives of patients, their family members, and healthcare providers on the use of family-administered delirium detection tools to detect delirium in critically ill patients and barriers and facilitators to using family-administered delirium detection tools in patient care. METHODS: In this qualitative study, critical care providers (five physicians, six registered nurses) and participants from the Family ICU Delirium Detection Study (seven past patients and family members) took part in four focus groups at one hospital in Calgary, Alberta. RESULTS: Key themes identified following thematic analysis from 18 participants included: 1) perceptions of acceptability of family-administered delirium detection (e.g., family feels valued, intensive care unit (ICU) care team may not use a family member's results, intensification of work load), 2) considerations regarding feasibility (e.g., insufficient knowledge, healthcare team buy-in), and 3) overarching strategies to support implementation into routine patient care (e.g., value of family-administered delirium detection for patients and families is well understood in the clinical context, regular communication between the family and ICU providers, an electronic version of the tool). CONCLUSIONS: Patients, family members and healthcare providers who participated in the focus groups perceived family participation in delirium detection and the use of family-administered delirium detection tools at the bedside as feasible and of value to patient care and family member coping. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT03379129); registered 15 December 2017.

RéSUMé: OBJECTIF: Bien que certaines études rapportent les perceptions concernant la participation de la famille à la prévention du delirium, on connaît peu l'utilisation d'outils de détection du delirium administrés par la famille dans les soins aux patients gravement malades. Cette étude a cherché à connaître les points de vue des patients, des membres de leur famille et des fournisseurs de soins de santé concernant l'utilisation d'outils de détection de delirium administrés par la famille pour dépister le delirium chez les patients gravement malades. Nous nous sommes aussi intéressés aux obstacles et aux éléments facilitateurs d'une utilisation d'outils de détection du delirium administrés par la famille dans les soins aux patients. MéTHODE: Dans le cadre de cette étude qualitative, les fournisseurs de soins intensifs (cinq médecins, six infirmières) et les participants de l'Étude sur la détection familiale du delirium aux soins intensifs (sept anciens patients et des membres de leur famille) ont participé à quatre groupes de discussion dans un hôpital de Calgary, en Alberta. RéSULTATS: Les principaux thèmes identifiés à la suite de l'analyse thématique de 18 participants étaient les suivants : 1) les perceptions de l'acceptabilité de la détection du delirium administrée par la famille (p. ex., la famille se sent valorisée, l'équipe de soins intensifs (USI) pourrait ne pas utiliser les résultats d'un membre de la famille, l'augmentation de la charge de travail), 2) les considérations concernant la faisabilité (par ex., connaissances insuffisantes, endossement par l'équipe de soins), et 3) les stratégies globales pour appuyer la mise en œuvre de cette modalité dans les soins de routine (p. ex., la valeur de la détection du delirium administrée par la famille pour les patients et les familles est bien comprise dans le contexte clinique, la communication régulière entre la famille et les fournisseurs de soins intensifs, une version électronique de l'outil). CONCLUSION: Les patients, les membres de la famille et les fournisseurs de soins de santé qui ont participé aux groupes de discussion ont perçu la participation de la famille à la détection du delirium et l'utilisation d'outils de détection du delirium administrés par la famille au chevet comme étant faisables et utiles pour les soins aux patients et les membres de la famille. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03379129); enregistrée le 15 décembre 2017.

Elevated ß-catenin activity contributes to carboplatin resistance in A2780cp ovarian cancer cells.

Ovarian cancer is the fifth leading cause of cancer-related mortalities in women. Epithelial ovarian cancer (EOC) represents approximately 90% of all ovarian malignancies. Most EOC patients are diagnosed at advanced stages and current chemotherapy regimens are ineffective against advanced EOC due to the development of chemoresistance. It is important to better understand the molecular mechanisms underlying acquired resistance to effectively manage this disease. In this study, we examined the expression of the Wnt/ß-catenin signaling components in the paired cisplatin-sensitive (A2780s) and cisplatin-resistant (A2780cp) EOC cell lines. Our results showed that several negative regulators of Wnt signaling are downregulated, whereas a few Wnt ligands and known Wnt/ß-catenin target genes are upregulated in A2780cp cells compared to A2780s cells, suggesting that Wnt/ß-catenin signaling is more active in A2780cp cells. Further analysis revealed nuclear localization of ß-catenin and higher ß-catenin transcriptional activity in A2780cp cells compared to A2780s cells. Finally, we demonstrated that chemical inhibition of ß-catenin transcriptional activity by its inhibitor CCT036477 sensitized A2780cp cells to carboplatin, supporting a role for ß-catenin in carboplatin resistance in A2780cp cells. In conclusion, our data suggest that increased Wnt/ß-catenin signaling activity contributes to carboplatin resistance in A2780cp cells.

RUNX3 contributes to carboplatin resistance in epithelial ovarian cancer cells.

OBJECTIVE: Resistance to platinum-based therapeutic agents represents a major hurdle in the treatment of epithelial ovarian cancer (EOC). There is an urgent need to better understand the underlying mechanisms. Here, we investigated the role of RUNX3 in carboplatin resistance in EOC cells. METHODS: Expression of RUNX3 was determined in human EOC cell line A2780s (cisplatin-sensitive) and A2780cp (cisplatin-resistant), human ovarian surface epithelium (OSE) and primary EOC cells. The effects of RUNX3 expression on sensitivity to carboplatin were determined in A2780s and A2780cp cells using neutral red uptake and clonogenic assays. Carboplatin-induced apoptosis was determined by measuring cleaved PARP using Western blotting. The expression of cellular inhibitor of apoptosis protein-2 (cIAP2) and its regulation by RUNX3 were assessed by quantitative RT-PCR and Western blotting. RESULTS: The expression of RUNX3 was elevated in A2780cp cells compared to A2780s cells and in EOC tissues from chemoresistant patients compared to those from chemosensitive patients. Overexpression of RUNX3 rendered A2780s cells more resistant to carboplatin, whereas inhibition of RUNX3 increased sensitivity to carboplatin in A2780cp cells. Inhibition of RUNX3 potentiated carboplatin-induced apoptosis in A2780cp cells as demonstrated by more pronounced PARP cleavage. Interestingly, the expression of cIAP2 was elevated in A2780cp cells compared to A2780s cells. Overexpression of RUNX3 increased cIAP2 expression in A2780s cells, whereas inhibition of RUNX3 decreased cIAP2 expression and potentiated carboplatin-induced decrease of cIAP2 in A2780cp cells. CONCLUSIONS: RUNX3 contributes to carboplatin resistance in EOC cells and may hold promise as a therapeutic target to treat EOC and/or a biomarker to predict chemoresistance.

Improving gender equity in critical care medicine: a protocol to establish priorities and strategies for implementation.

INTRODUCTION: While the number of women entering medical school now equals or surpasses the number of men, gender equity in medicine has not been achieved. Women continue to be under-represented in leadership roles (eg, deans, medical chairs) and senior faculty positions. In addition, women do not enter medical specialties as often as men, which can have important implications for work environment, reimbursement and the delivery of patient care. Compared with other medical specialties (eg, anaesthesiology, dermatology, etc), critical care medicine is a medical specialty with some of the lowest representation of women. While strategies to improve gender equity in critical care medicine exist in the published literature, efforts to comprehensively synthesise, prioritise and implement solutions have been limited.The objective of this programme of work is to establish priorities for the development and implementation of key strategies to improve the outcomes, well-being and experiences of women in critical care in Canada. METHODS AND ANALYSIS: Three phases encompass this programme of work. In phase I, we will catalogue published strategies focused on improving gender inequity across medical specialties through a scoping review. In phase II, we will conduct a modified Delphi consensus process with decision-makers, physicians and researchers to identify key strategies (identified in phase I and proposed by participants in phase II) for improving gender inequity in the specialty of critical care medicine. Finally, in phase III, we will conduct a 1-day stakeholder meeting that engages participants from phase II to build capacity for the development and implementation of top ranked strategies. Data analyses from this programme of work will be both quantitative and qualitative. ETHICS AND DISSEMINATION: The proposed programme of work is a foundational step towards establishing targeted strategies to improve gender inequity in the medical specialty of critical care medicine. Strategies will be prioritised by stakeholders, mapped to preidentified drivers of gender equity in the specialty and be scalable to institutional needs. A final report of our results including the list of top prioritised strategies and implementation objectives will be disseminated to panel participants, critical care leadership teams and major critical care societies who are partners in this work, around the country to facilitate uptake at the local level.The University of Calgary Conjoint Health Research Ethics Board has approved this study (REB16-0890).

Post-transplant lymphoproliferative disorder and management of residual mass post chemotherapy: Case report.

INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a rare complication. It represents a spectrum of lymphoid proliferations which occur in the setting of immunosuppression and organ transplantation. There are no reported cases or recommendations for the treatment of residual masses post rituximab of PTLD. PRESENTATION OF CASE: A patient with a long standing history of immunosuppression due to multiple kidney transplants starting in 1979, presented with a very large palpable hard abdominal mass (2004) after a fourth renal transplant. There was a past history of heavy immune suppression. CT scans revealed a conglomerate mass involving the right native kidney and two prior right sided renal allografts that crossed the midline. Biopsy of the large right retroperitoneal mass revealed large B cell lymphoma (CD 20 positive); consistent with post-transplant lymphoproliferative disorder (PTLD). DISCUSSION: Management of bulky PTLD, in a highly sensitized, heavily immune suppressed patient is not well described in the literature. The mainstay of therapy is IR and Ritixumab (R) monotherapy and combination R-CHOP. CHOP chemotherapy has an associated mortality rate of up to 38%. Radiotherapy is often considered over surgery and surgery has been most frequently used when associated with bowel complications. In this case report we describe upfront Ritiximab followed by consolidation resection and cytotoxic chemotherapy as a management strategy to reduce toxicity. CONCLUSION: The approach taken by our surgical team illustrates the benefits of disease debulking in certain cases of PTLD, by guiding further therapy and spacing and reducing chemotherapy in immune suppressed patients.