BTG1 inactivation drives lymphomagenesis and promotes lymphoma dissemination through activation of BCAR1.

Understanding the functional role of mutated genes in cancer is required to translate the findings of cancer genomics into therapeutic improvement. BTG1 is recurrently mutated in the MCD/C5 subtype of diffuse large B-cell lymphoma (DLBCL), which is associated with extranodal dissemination. Here, we provide evidence that Btg1 knock out accelerates the development of a lethal lymphoproliferative disease driven by Bcl2 overexpression. Furthermore, we show that the scaffolding protein BCAR1 is a BTG1 partner. Moreover, after BTG1 deletion or expression of BTG1 mutations observed in patients with DLBCL, the overactivation of the BCAR1-RAC1 pathway confers increased migration ability in vitro and in vivo. These modifications are targetable with the SRC inhibitor dasatinib, which opens novel therapeutic opportunities in BTG1 mutated DLBCL.

Patient engagement in health implementation research: A logic model.

INTRODUCTION: Growing evidence supports patient engagement (PE) in health implementation research to improve the quality, relevance and uptake of research. However, more guidance is needed to plan and operationalize PE before and throughout the research process. The aim of the study was to develop a logic model illustrating the causal links between context, resources, activities, outcomes and impact of PE in an implementation research programme. METHODS: The Patient Engagement in Health Implementation Research Logic Model (hereafter the Logic Model) was developed using a descriptive qualitative design with a participatory approach, in the context of the PriCARE programme. This programme aims to implement and evaluate case management for individuals who frequently use healthcare services in primary care clinics across five Canadian provinces. Participant observation of team meetings was performed by all team members involved in the programme and in-depth interviews were conducted by two external research assistants with team members (n = 22). A deductive thematic analysis using components of logic models as coding categories was conducted. Data were pooled in the first version of the Logic Model, which was refined in research team meetings with patient partners. The final version was validated by all team members. RESULTS: The Logic Model highlights the importance of integrating PE into the project before its commencement, with appropriate support in terms of funding and time allocation. The governance structure and leadership of both principal investigators and patient partners have significant effects on PE activities and outcomes. As an empirical and standardized illustration that facilitates a shared understanding, the Logic Model provides guidance for maximizing the impact of patient partnership in various contexts for research, patients, providers and health care. CONCLUSION: The Logic Model will help academic researchers, decision makers and patient partners plan, operationalize, and assess PE in implementation research for optimal outcomes. PATIENT OR PUBLIC CONTRIBUTION: Patient partners from the PriCARE research programme contributed to developing the research objectives and designing, developing and validating data collection tools, producing data, developing and validating the Logic Model and reviewing the manuscript.

Implementation analysis of a case management intervention for people with complex care needs in primary care: a multiple case study across Canada.

BACKGROUND: Case management is one of the most frequently performed interventions to mitigate the negative effects of high healthcare use on patients, primary care providers and the healthcare system. Reviews have addressed factors influencing case management interventions (CMI) implementation and reported common themes related to the case manager role and activities, collaboration with other primary care providers, CMI training and relationships with the patients. However, the heterogeneity of the settings in which CMI have been implemented may impair the transferability of the findings. Moreover, the underlying factors influencing the first steps of CMI implementation need to be further assessed. This study aimed to evaluate facilitators and barriers of the first implementation steps of a CMI by primary care nurses for people with complex care needs who frequently use healthcare services. METHODS: A qualitative multiple case study was conducted including six primary care clinics across four provinces in Canada. In-depth interviews and focus groups with nurse case managers, health services managers, and other primary care providers were conducted. Field notes also formed part of the data. A mixed thematic analysis, deductive and inductive, was carried out. RESULTS: Leadership of the primary care providers and managers facilitated the first steps of the of CMI implementation, as did the experience and skills of the nurse case managers and capacity development within the teams. The time required to establish CMI was a barrier at the beginning of the CMI implementation. Most nurse case managers expressed apprehension about developing an "individualized services plan" with multiple health professionals and the patient. Clinic team meetings and a nurse case managers community of practice created opportunities to address primary care providers' concerns. Participants generally perceived the CMI as a comprehensive, adaptable, and organized approach to care, providing more resources and support for patients and better coordination in primary care. CONCLUSION: Results of this study will be useful for decision makers, care providers, patients and researchers who are considering the implementation of CMI in primary care. Providing knowledge about first steps of CMI implementation will also help inform policies and best practices.

Implementation analysis of case management interventions for frequent users of healthcare services: A multiple-case study.

Context. Case management interventions (CMIs) are recognized to improve patients' experience of integrated care, to promote better utilization of healthcare resources, and to reduce emergency department visits, hospitalizations and health care costs. However, contextual factors influencing implementation of CMIs in primary care settings in Canada still need to be studied. Objective. To examine facilitators and barriers influencing implementation planning, engagement of key actors and the start-up phases of a CMI led by nurse case managers for frequent users of healthcare services with chronic diseases and complex care needs. Study design. Qualitative multiple case study design. Setting. Six primary care clinics across four provinces in Canada. Population studied. Frequent users of healthcare services with chronic diseases and complex care needs. Intervention. A CMI led by nurse case managers that included four main components: 1) patient needs assessment; 2) care planning, including an individual services plan (ISP); 3) coordination of services among health and social services partners; 4) self-management support for patients and families. Methods. Data collection: in-depth interviews with nurse case managers (n=10), clinic managers (n=5), and other healthcare professionals (n=5); six focus groups with family physicians (n=20), and other healthcare professionals (n=8); and field notes by research coordinators. Analysis: Mixed descriptive thematic analysis; intra-case histories; systematic comparison among cases by means of a descriptive and interpretative matrix; investigator and patient partners triangulation. Outcome Measures. Factors influencing the implementation of the CMI in primary care settings. Results. Difficulty of access to patient hospital information is a common barrier to all cases, as well as identification and recruitment of patients with the greatest needs of a CMI. Nurse case managers need extra time in the short term, especially when preparing and conducting the ISP. On the other hand, a culture of patient-centredness and collaboration; managerial and clinical leadership and support; and a positive perception of the CMI alongside provider engagement helps to overcome these barriers. Conclusions. This study may help researchers, decision-makers and clinicians plan the implementation of CMIs in primary care settings for frequent users of healthcare services with chronic diseases and complex care needs.

Planning, operationalizing, and evaluating patient partners' engagement in primary care research: a logic model.

Context. There is growing evidence supporting patients' engagement (PE) in primary care research to improve the quality, relevance, and uptake of research. However, guidance is still needed to plan and operationalize this engagement during the research process. Objective. To develop a logic model illustrating empirically the causal links between context, resources, activities, and expected outcomes of PE in an implementation research program in primary care. Study design. Instrumental case study. Setting. A research program (PriCARE) aiming to implement and evaluate a case management intervention (CMI) in primary care clinics across five provinces in Canada. Population studied. Research team members. Methods. Data collection. Participant observation and in-depth interviews (n=22) conducted by two independent research assistants with research team members: principal investigators (n=5); co-investigators (n=2); research coordinators and assistants (n=8); and patient partners (n=7). Analysis. Deductive thematic analysis using components of the logic model as coding categories. All data were coded using NVivo 12 software. Data were reduced and organized in a first logic model version. Team meetings helped to refine the logic model. The final version was validated by all research team members. Results. The logic model provides an empirical illustration of the relationship between context, resources, activities, and expected outcomes for PE. Mobilized resources (human, financial, organizational, and communicational) allow research team members to be involved in many activities related to PE: recruitment, training, and support of patient partners; development of a governance structure; participation in research activities; agreement on decision-making processes; training and support of clinicians; development of tools for patients' involvement in the CMI. These activities lead to the following benefits for health research: improved communication amongst all team members, results and knowledge translation; development of a PE culture; capacity building; democratization of health research; and for healthcare: improved implementation of the intervention; improved patient engagement in their care; better health outcomes and resource utilization; support of decision-makers and clinicians; and better practices. Conclusions. The logic model may be useful for the planning, operationalization and evaluation of PPE in primary care research programs.

Patient engagement works: Patient and researcher experiences of patient partnership in primary healthcare research.

Context: Health researchers are increasingly engaging patients and their families as partners in the research process, from inception to knowledge translation. The trend toward 'patient-oriented' research is encouraged by a growing view that studies which integrate the patient perspective will make better use of resources to produce more relevant evidence that can be more easily translated to clinical settings. While there is an emerging literature on best practices, challenges, and learnings related to patient engagement (PE), few studies consider the experiences of patient partners (PP) and researchers in the same project. This presentation will present PP and researcher experiences of PE, highlighting important similarities and differences and proposing recommendations. Objectives: To characterize PE experience from the perspective of researchers and PP working together on the same research program, PriCARE; to identify successes and challenges; to ascertain contributions of PE in health research. Study Design: Qualitative. Setting or Dataset: This study was conducted within the larger 5-province PriCARE study examining a nurse-led case management intervention for primary care patients with complex needs. Population studied: 22 members of the study team (7 PP, 8 coordinators, 2 co-investigators, 5 principal investigators). Methods: Data collection: In-depth interviews using guides co-created by researchers and PP covering topics such as PE-related training and knowledge, and reflections on PE processes and impact. Research assistants external to the PriCARE study conducted interviews, transcribed researcher interviews, and generated a summary of PP interviews. Analysis: Data were analyzed thematically using a coding framework that was co-developed with PP. Outcome Measures: Researcher and patient experiences of PE, PP contributions to health research. Results: All team members need PE training at the beginning of and throughout the research process. Evolving trust and flexibility helped team members to navigate different experiences and priorities. PP make integral contributions to study and instrument design, data analysis, and knowledge translation. Clear expectations about the degree and nature of PE and team members' roles are critical. Conclusions: Meaningful PE requires patient-researcher partnership and clear expectation setting at the outset and throughout the research process, and ongoing flexibility to adapt.

Reconciling validity and challenges of patient comfort and understanding: Guidelines to patient-oriented questionnaires.

BACKGROUND: Patient-reported outcome measures (PROMs) are widely recognized as important tools for achieving a patient-centred approach in health research. While PROMs are subject to several stages of validation during development, even questionnaires with robust psychometric properties may challenge patient comfort and understanding. AIM: Building on the experience of patient engagement in the PriCARE research programme, this paper outlines the team's response to concerns raised by patient partners regarding the administration of the questionnaire. METHODS: Based on a participatory action research design and the patient engagement framework in the Strategy for Patient-Oriented Research of the Canadian Institutes of Health Research, PriCARE team members worked together to discuss concerns, review the questionnaires and come up with solutions. Data were collected through participant observation of team meetings. RESULTS: This paper demonstrates how patient partners were engaged in PriCARE and integrated into the programme's governance structure, focusing on the challenges that they raised regarding the questionnaires and how these were addressed by PriCARE team members in a six-step approach: (1) Recognizing patient partner concerns, discussing concerns and reframing the challenges; (2) Detailing and sharing evidence of the validity of the questionnaires; (3) Evaluating potential solutions; (4) Searching the literature for guidelines; (5) Creating guidelines; and (6) Sharing and refining guidelines. CONCLUSION: This six-step approach demonstrates how research teams can integrate patient partners as equal members, develop meaningful collaboration through recognition of individual experiences and expertise and ensure that the patient perspective is taken into consideration in research and healthcare innovation. PATIENT OR PUBLIC CONTRIBUTION: All patient partners from the PriCARE programme were actively involved in the six-step approach. They were also involved in the preparation of the manuscript.

Patient and researcher experiences of patient engagement in primary care health care research: A participatory qualitative study.

BACKGROUND: Studies have highlighted common challenges and barriers to patient engagement in research, but most were based on patient partners' or academic researchers' experiences. A better understanding of how both groups differentially experience their partnership could help identify strategies to improve collaboration in patient engagement research. AIM: This study aimed to describe and compare patient partners' and academic researchers' experiences in patient engagement research. METHODS: Based on a participatory approach, a descriptive qualitative study was conducted with patient partners and academic researchers who are involved in the PriCARE research programme in primary health care to examine their experience of patient engagement. Individual semi-structured interviews with patient partners (n = 7) and academic researchers (n = 15) were conducted. Academic researchers' interview verbatims, deidentified patient partners' summaries of their interviews and summaries of meetings with patient partners were analysed using inductive thematic analysis in collaboration with patient partners. RESULTS: Patient partners and academic researchers' experiences with patient engagement are captured within four themes: (1) evolving relationships; (2) creating an environment that fosters patient engagement; (3) striking a balance; and (4) impact and value of patient engagement. Evolving relationships refers to how partnerships grew and improved over time with an acceptance of tensions and willingness to move beyond them, two-way communication and leadership of key team members. Creating an environment that fosters patient engagement requires appropriate structural support, such as clear descriptions of patient partner roles; adequate training for all team members; institutional guidance on patient engagement; regular and appropriate translation services; and financial assistance. For patient partners and academic researchers, striking a balance referred to the challenge of reconciling patient partners' interests and established research practices. Finally, both groups recognized the value and positive impact of patient engagement in the programme in terms of improving the relevance of research and the applicability of results. While patient partners and academic researchers identified similar challenges and strategies, their experiences of patient engagement differed according to their own backgrounds, motives and expectations. CONCLUSION: Both patient partners and academic researchers highlighted the importance of finding a balance between providing structure or guidelines for patient engagement, while allowing for flexibility along the way. PATIENT OR PUBLIC CONTRIBUTION: Patient partners from the PriCARE research programme were involved in the following aspects of the current study: (1) development of the research objectives; (2) planning of the research design; (3) development and validation of data collection tools (i.e., interview guides); (4) production of data (i.e., acted as interviewees); (5) validation of data analysis tools (code book); (6) analysis of qualitative data; and (7) drafting of the manuscript and contributing to other knowledge translation activities, such as conference presentations and the creation of a short animated video.

Better understanding care transitions of adults with complex health and social care needs: a study protocol.

BACKGROUND: Adults with chronic conditions who also suffer from mental health comorbidities and/or social vulnerability require services from many providers across different sectors. They may have complex health and social care needs and experience poorer health indicators and high mortality rates while generating considerable costs to the health and social services system. In response, the literature has stressed the need for a collaborative approach amongst providers to facilitate the care transition process. A better understanding of care transitions is the next step towards the improvement of integrated care models. The aim of the study is to better understand care transitions of adults with complex health and social care needs across community, primary care, and hospital settings, combining the experiences of patients and their families, providers, and health managers. METHODS/DESIGN: We will conduct a two-phase mixed methods multiple case study (quantitative and qualitative). We will work with six cases in three Canadian provinces, each case being the actual care transitions across community, primary care, and hospital settings. Adult patients with complex needs will be identified by having visited the emergency department at least three times over the previous 12 months. To ensure they have complex needs, they will be invited to complete INTERMED Self-Assessment and invited to enroll if positive. For the quantitative phase, data will be obtained through questionnaires and multi-level regression analyses will be conducted. For the qualitative phase, semi-structured interviews and focus groups will be conducted with patients, family members, care providers, and managers, and thematic analysis will be performed. Quantitative and qualitative results will be compared and then merged. DISCUSSION: This study is one of the first to examine care transitions of adults with complex needs by adopting a comprehensive vision of care transitions and bringing together the experiences of patients and family members, providers, and health managers. By using an integrated knowledge translation approach with key knowledge users, the study's findings have the potential to inform the optimization of integrated care, to positively impact the health of adults with complex needs, and reduce the economic burden to the health and social care systems.

Case Study With a Participatory Approach: Rethinking Pragmatics of Stakeholder Engagement for Implementation Research.

The case study design is particularly useful for implementation analysis of complex health care innovations in primary care that can be influenced by the context of dynamic environments. Case studies may be combined with participatory approaches where academics conduct joint research with nonacademic stakeholders, to foster translation of findings results into practice. The aim of this article is to clarify epistemological and methodological considerations of case studies with a participatory approach. It also aims to propose best practice recommendations when using this case study approach. We distinguish between the participatory case study with full co-construction and co-governance, and the case study with a participatory approach whereby stakeholders are consulted in certain phases of the research. We then compare the epistemological posture of 3 prominent case study methodologists, Yin, Stake, and Merriam, to present the epistemological posture of case studies with a participatory approach. The relevance, applications, and procedures of a case study with a participatory approach methodology are illustrated through a concrete example of a primary care research program (PriCARE). We propose 12 steps for designing and conducting a case study with a participatory approach that may help guide researchers in the implementation analysis of complex health care innovations in primary care.

Beta-arrestins operate an on/off control switch for focal adhesion kinase activity.

Focal adhesion kinase (FAK) regulates key biological processes downstream of G protein-coupled receptors (GPCRs) in normal and cancer cells, but the modes of kinase activation by these receptors remain unclear. We report that after GPCR stimulation, FAK activation is controlled by a sequence of events depending on the scaffolding proteins ß-arrestins and G proteins. Depletion of ß-arrestins results in a marked increase in FAK autophosphorylation and focal adhesion number. We demonstrate that ß-arrestins interact directly with FAK and inhibit its autophosphorylation in resting cells. Both FAK-ß-arrestin interaction and FAK inhibition require the FERM domain of FAK. Following the stimulation of the angiotensin receptor AT1AR and subsequent translocation of the FAK-ß-arrestin complex to the plasma membrane, ß-arrestin interaction with the adaptor AP-2 releases inactive FAK from the inhibitory complex, allowing its activation by receptor-stimulated G proteins and activation of downstream FAK effectors. Release and activation of FAK in response to angiotensin are prevented by an AP-2-binding deficient ß-arrestin and by a specific inhibitor of ß-arrestin/AP-2 interaction; this inhibitor also prevents FAK activation in response to vasopressin. This previously unrecognized mechanism of FAK regulation involving a dual role of ß-arrestins, which inhibit FAK in resting cells while driving its activation at the plasma membrane by GPCR-stimulated G proteins, opens new potential therapeutic perspectives in cancers with up-regulated FAK.

A PIM-CHK1 signaling pathway regulates PLK1 phosphorylation and function during mitosis.

Although the kinase CHK1 is a key player in the DNA damage response (DDR), several studies have recently provided evidence of DDR-independent roles of CHK1, in particular following phosphorylation of its S280 residue. Here, we demonstrate that CHK1 S280 phosphorylation is cell cycle-dependent and peaks during mitosis. We found that this phosphorylation was catalyzed by the kinase PIM2, whose protein expression was also increased during mitosis. Importantly, we identified polo-like kinase 1 (PLK1) as a direct target of CHK1 during mitosis. Genetic or pharmacological inhibition of CHK1 reduced the activating phosphorylation of PLK1 on T210, and recombinant CHK1 was able to phosphorylate T210 of PLK1 in vitro Accordingly, S280-phosphorylated CHK1 and PLK1 exhibited similar specific mitotic localizations, and PLK1 was co-immunoprecipitated with S280-phosphorylated CHK1 from mitotic cell extracts. Moreover, CHK1-mediated phosphorylation of PLK1 was dependent on S280 phosphorylation by PIM2. Inhibition of PIM proteins reduced cell proliferation and mitotic entry, which was rescued by expressing a T210D phosphomimetic mutant of PLK1. Altogether, these data identify a new PIM-CHK1-PLK1 phosphorylation cascade that regulates different mitotic steps independently of the CHK1 DDR function.This article has an associated First Person interview with the first author of the paper.

Case Management in Primary Care for Frequent Users of Health Care Services: A Realist Synthesis.

PURPOSE: Case management (CM) is a promising intervention for frequent users of health care services. Our research question was how and under what circumstances does CM in primary care work to improve outcomes among frequent users with chronic conditions? METHODS: We conducted a realist synthesis, searching MEDLINE, CINAHL, Embase, and PsycINFO (1996 to September 2017) for articles meeting the following criteria: (1) population: adult frequent users with chronic disease, (2) intervention: CM in a primary care setting with a postintervention evaluation, and (3) primary outcomes: integration of services, health care system use, cost, and patient outcome measures. Academic and gray literature were evaluated for relevance and robustness. Independent reviewers extracted data to identify context, mechanism, and outcome (CMO) configurations. Analysis of CMO configurations allowed for the modification of an initial program theory toward a refined program theory. RESULTS: Of the 9,295 records retrieved, 21 peer-reviewed articles and an additional 89 documents were retained. We evaluated 19 CM interventions and identified 11 CMO configurations. The development of a trusting relationship fostering patient and clinician engagement in the CM intervention was recurrent in many CMO configurations. CONCLUSION: Our refined program theory proposes that in the context of easy access to an experienced and trusted case manager who provides comprehensive care while maintaining positive interactions with patients, the development of this relationship fosters the engagement of both individuals and yields positive outcomes when the following mechanisms are triggered: patients and clinicians feel supported, respected, accepted, engaged, and committed; and patients feel less anxious, more secure, and empowered to self-manage.

Characteristics of Case Management in Primary Care Associated With Positive Outcomes for Frequent Users of Health Care: A Systematic Review.

PURPOSE: Case management (CM) interventions are effective for frequent users of health care services, but little is known about which intervention characteristics lead to positive outcomes. We sought to identify characteristics of CM that yield positive outcomes among frequent users with chronic disease in primary care. METHODS: For this systematic review of both quantitative and qualitative studies, we searched MEDLINE, CINAHL, Embase, and PsycINFO (1996 to September 2017) and included articles meeting the following criteria: (1)population: adult frequent users with chronic disease, (2)intervention: CM in a primary care setting with a postintervention evaluation, and (3)primary outcomes: integration of services, health care system use, cost, and patient outcome measures. Independent reviewers screened abstracts, read full texts, appraised methodologic quality (Mixed Methods Appraisal Tool), and extracted data from the included studies. Sufficient and necessary CM intervention characteristics were identified using configurational comparative methods. RESULTS: Of the 10,687 records retrieved, 20 studies were included; 17 quantitative, 2 qualitative, and 1 mixed methods study. Analyses revealed that it is necessary to identify patients most likely to benefit from a CM intervention for CM to produce positive outcomes. High-intensity intervention or the presence of a multidisciplinary/interorganizational care plan was also associated with positive outcomes. CONCLUSIONS: Policy makers and clinicians should focus on their case-finding processes because this is the essential characteristic of CM effectiveness. In addition, value should be placed on high-intensity CM interventions and developing care plans with multiple types of care providers to help improve patient outcomes.

Case Management in Primary Care for Frequent Users of Health Care Services: A Mixed Methods Study.

PURPOSE: This study aimed to evaluate the effects of the V1SAGES case management intervention (Vulnerable Patients in Primary Care: Nurse Case Management and Self-management Support) for frequent users of health care services with chronic disease and complex care needs on psychological distress and patient activation. METHODS: We used a 2-phase sequential mixed methods design. The first phase was a pragmatic randomized controlled trial with intention-to-treat analysis that measured the effects of the intervention compared with usual care on psychological distress and patient activation before and after 6 months. The second phase had a qualitative descriptive design and entailed thematic analysis of in-depth interviews (25 patients, 6 case management nurses, 9 health managers) and focus groups (8 patients' spouses, 21 family physicians) to understand stakeholders' perceived effects of the intervention on patients. RESULTS: A total of 247 patients were randomized into the intervention group (n = 126) or the control group (n = 121). Compared with usual care, the intervention reduced psychological distress (odds ratio = 0.43; 95% CI, 0.19-0.95, P = .04), but did not have any significant effect on patient activation (P = .43). Qualitative results suggested that patients and their spouses benefitted from the case management intervention, gaining a sense of security, and stakeholders noted better patient self-management of health. CONCLUSIONS: Together, our study's quantitative and qualitative results suggest that case management reduces psychological distress, making patients and caregivers feel more secure, whereas impact on self-management is unclear. Case management is a promising avenue to improve outcomes among frequent users of health care with complex needs.

Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition.

Cancer cells require glutamine to adapt to increased biosynthetic activity. The limiting step in intracellular glutamine catabolism involves its conversion to glutamate by glutaminase (GA). Different GA isoforms are encoded by the genes GLS1 and GLS2 in humans. Herein, we show that glutamine levels control mitochondrial oxidative phosphorylation (OXPHOS) in acute myeloid leukemia (AML) cells. Glutaminase C (GAC) is the GA isoform that is most abundantly expressed in AML. Both knockdown of GLS1 expression and pharmacologic GLS1 inhibition by the drug CB-839 can reduce OXPHOS, leading to leukemic cell proliferation arrest and apoptosis without causing cytotoxic activity against normal human CD34(+) progenitors. Strikingly, GLS1 knockdown dramatically inhibited AML development in NSG mice. The antileukemic activity of CB-839 was abrogated by both the expression of a hyperactive GAC(K320A) allele and the addition of the tricarboxyclic acid cycle product α-ketoglutarate, indicating the critical function of GLS1 in AML cell survival. Finally, glutaminolysis inhibition activated mitochondrial apoptosis and synergistically sensitized leukemic cells to priming with the BCL-2 inhibitor ABT-199. These findings show that targeting glutamine addiction via GLS1 inhibition offers a potential novel therapeutic strategy for AML.

The Chronic Disease Self-Management Program: the experience of frequent users of health care services and peer leaders.

BACKGROUND: Large amount of evidence supports the contribution of the Stanford Chronic Disease Self-Management Program (CDSMP) to a global chronic disease management strategy. However, many studies have suggested further exploring of the factors influencing acceptance and completion of participants in this program. OBJECTIVE: This study aimed to describe and examine factors associated with acceptance and completion rates of the CDSMP among frequent users of health care services, and to highlight the experience of patients and peer leaders who facilitated the program. METHODS: A descriptive design with mixed sequential data was used. Acceptance and completion rates were calculated and their relationship with patient characteristics was examined in regression analysis (n = 167). Interviews were conducted among patients who accepted (n = 11) and refused (n = 13) to participate and with the program coordinator. Focus groups were held with the seven peer leaders who facilitated the program. Data were analysed using thematic analysis. RESULTS: Of the 167 patients invited, 60 (36%) accepted to participate in the program. Group format was the most frequent reason to decline the invitation to participate. Twenty-eight participants (47%) completed the program. Participants who dropped out during the program raised different reasons such as poor health and too much heterogeneity among participants. Factors such as location, schedule, content, group composition and facilitation were considered as important elements contributing to the success of the program. CONCLUSION: The CDSMP could therefore be considered as a self-management support option for this vulnerable clientele, while taking measures to avoid too much heterogeneity among participants to improve completion rates.

Medical education for equity in health: a participatory action research involving persons living in poverty and healthcare professionals.

BACKGROUND: Improving the knowledge and competencies of healthcare professionals is crucial to better address the specific needs of persons living in poverty and avoid stigmatization. This study aimed to explore the needs and expectations of persons living in poverty and healthcare professionals in terms of medical training regarding poverty and its effects on health and healthcare. METHODS: We conducted a participatory action research study using photovoice, a method using photography, together with merging of knowledge and practice, an approach promoting dialogue between different sources of knowledge. Nineteen healthcare professionals and persons from an international community organization against poverty participated in the study. The first phase included 60 meetings and group sessions to identify the perceived barriers between persons living in poverty and healthcare teams. In the second phase, sub-committees deployed action plans in academic teaching units to overcome barriers identified in the first phase. Data were analysed through thematic analysis, using NVivo, in collaboration with five non-academic co-researchers. RESULTS: Four themes in regard to medical training were highlighted: improving medical students' and residents' knowledge on poverty and the living conditions of persons living in poverty; improving their understanding of the reality of those people; improving their relational skills pertaining to communication and interaction with persons living in poverty; improving their awareness and capacity for self-reflection. At the end of the second phase, actions were undertaken such as improving knowledge of the living conditions of persons living in poverty by posting social assistance rates, and tailoring interventions to patients' reality by including sociodemographic information in electronic medical records. Our findings also led to a participatory research project aiming to improve the skills and competency of residents and health professionals in regard to the quality of healthcare provided to persons living in poverty. CONCLUSIONS: Medical training and residency programs should aim to improve students' and residents' relational skills, more specifically their communication skills, as well as their awareness and capacity for self-reflection, by helping them to identify and recognize their biases, and limitations.

Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia.

Cancer cells require nutrients and energy to adapt to increased biosynthetic activity, and protein synthesis inhibition downstream of mammalian target of rapamycin complex 1 (mTORC1) has shown promise as a possible therapy for acute myeloid leukemia (AML). Glutamine contributes to leucine import into cells, which controls the amino acid/Rag/mTORC1 signaling pathway. We show in our current study that glutamine removal inhibits mTORC1 and induces apoptosis in AML cells. The knockdown of the SLC1A5 high-affinity transporter for glutamine induces apoptosis and inhibits tumor formation in a mouse AML xenotransplantation model. l-asparaginase (l-ase) is an anticancer agent also harboring glutaminase activity. We show that l-ases from both Escherichia coli and Erwinia chrysanthemi profoundly inhibit mTORC1 and protein synthesis and that this inhibition correlates with their glutaminase activity levels and produces a strong apoptotic response in primary AML cells. We further show that l-ases upregulate glutamine synthase (GS) expression in leukemic cells and that a GS knockdown enhances l-ase-induced apoptosis in some AML cells. Finally, we observe a strong autophagic process upon l-ase treatment. These results suggest that l-ase anticancer activity and glutamine uptake inhibition are promising new therapeutic strategies for AML.

Case Management in Primary Care for Frequent Users of Health Care Services With Chronic Diseases: A Qualitative Study of Patient and Family Experience.

PURPOSE: Although case management (CM) is increasingly being implemented to address the complex needs of vulnerable clienteles, few studies have examined the patient experience of CM. This study aimed to examine the experience of patients and their family members with care integration as part of a primary care CM intervention. Patients in the study were frequent users of health care services who had chronic diseases. METHODS: A descriptive, qualitative approach was conducted involving 25 patients and 8 of their family members. Data were collected through in-depth interviews of the patients and 2 focus groups of family members and were analyzed thematically. RESULTS: While some participants did not fully understand the CM intervention and a few believed that it involved too many appointments, the CM nurses were patients' preferred contact with primary care. The nurses actively involved the patients in developing and carrying out their individualized services plans (ISPs) with other health care partners. Patients felt that their needs were taken into consideration, especially regarding access to the health care system. The case manager facilitated access to information as well as communication and coordination among health care and community partners. This improved communication comforted the patients and nurtured a relationship of trust. Participants were actively involved in decision-making. Their ISPs helped them know where they were going and improved transitions between services. CONCLUSIONS: The experience of patients and family members was overall very positive regarding care integration. They reported improved access, communication, coordination, and involvement in decision-making as well as better health care transitions.