Advanced Cancer in Young Adults (YAs): Living in a Liminal Space.

Young adults (YAs), defined as individuals between the ages of 18 and 39 years, experience unique challenges when diagnosed with advanced cancer. Using the social constructivist grounded theory approach, we aimed to develop a theoretical understanding of how YAs live day to day with their diagnosis. A sample of 25 YAs (aged 22-39 years) with advanced cancer from across Canada participated in semi-structured interviews. Findings illustrate that the YAs described day-to-day life as an oscillating experience swinging between two opposing disease outcomes: (1) hoping for a cure and (2) facing the possibility of premature death. Oscillating between these potential outcomes was characterized as living in a liminal space wherein participants were unsure how to live from one day to the next. The participants oscillated at various rates, with different factors influencing the rate of oscillation, including inconsistent and poor messaging from their oncologists or treatment team, progression or regression of their cancer, and changes in their physical functioning and mental health. These findings provide a theoretical framework for designing interventions to help YAs adapt to their circumstance.

Efficacy of sustained knowledge translation (KT) interventions in chronic disease management in older adults: systematic review and meta-analysis of complex interventions.

BACKGROUND: Chronic disease management (CDM) through sustained knowledge translation (KT) interventions ensures long-term, high-quality care. We assessed implementation of KT interventions for supporting CDM and their efficacy when sustained in older adults. METHODS: Design: Systematic review with meta-analysis engaging 17 knowledge users using integrated KT. ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) including adults (> 65 years old) with chronic disease(s), their caregivers, health and/or policy-decision makers receiving a KT intervention to carry out a CDM intervention for at least 12 months (versus other KT interventions or usual care). INFORMATION SOURCES: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from each database's inception to March 2020. OUTCOME MEASURES: Sustainability, fidelity, adherence of KT interventions for CDM practice, quality of life (QOL) and quality of care (QOC). Data extraction, risk of bias (ROB) assessment: We screened, abstracted and appraised articles (Effective Practice and Organisation of Care ROB tool) independently and in duplicate. DATA SYNTHESIS: We performed both random-effects and fixed-effect meta-analyses and estimated mean differences (MDs) for continuous and odds ratios (ORs) for dichotomous data. RESULTS: We included 158 RCTs (973,074 participants [961,745 patients, 5540 caregivers, 5789 providers]) and 39 companion reports comprising 329 KT interventions, involving patients (43.2%), healthcare providers (20.7%) or both (10.9%). We identified 16 studies described as assessing sustainability in 8.1% interventions, 67 studies as assessing adherence in 35.6% interventions and 20 studies as assessing fidelity in 8.7% of the interventions. Most meta-analyses suggested that KT interventions improved QOL, but imprecisely (36 item Short-Form mental [SF-36 mental]: MD 1.11, 95% confidence interval [CI] [- 1.25, 3.47], 14 RCTs, 5876 participants, I2 = 96%; European QOL-5 dimensions: MD 0.01, 95% CI [- 0.01, 0.02], 15 RCTs, 6628 participants, I2 = 25%; St George's Respiratory Questionnaire: MD - 2.12, 95% CI [- 3.72, - 0.51] 44 12 RCTs, 2893 participants, I2 = 44%). KT interventions improved QOC (OR 1.55, 95% CI [1.29, 1.85], 12 RCTS, 5271 participants, I2 = 21%). CONCLUSIONS: KT intervention sustainability was infrequently defined and assessed. Sustained KT interventions have the potential to improve QOL and QOC in older adults with CDM. However, their overall efficacy remains uncertain and it varies by effect modifiers, including intervention type, chronic disease number, comorbidities, and participant age. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018084810.

Design and Synthesis of Inhibitors of the E3 Ligase SMAD Specific E3 Ubiquitin Protein Ligase 1 as a Treatment for Lung Remodeling in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a devastating rare disease, which despite currently available treatments, still represents a high unmet medical need. Specific E3 ubiquitin protein ligase 1 (SMURF1) is a HECT E3 ligase that ubiquitinates key signaling molecules from the TGFß/BMP pathways, which are of great relevance in the pathophysiology of PAH. Herein, the design and synthesis of novel potent small-molecule SMURF1 ligase inhibitors are described. Lead molecule 38 has demonstrated good oral pharmacokinetics in rats and significant efficacy in a rodent model of pulmonary hypertension.

The Transformation of Adolescent and Young Adult Oncological and Supportive Care in Canada: A Mixed Methods Study.

BACKGROUND: Due to ongoing disparity in the specialized care available to adolescents and young adults (AYAs) with cancer, this study aimed to understand the gaps and barriers to accessing care and preferences on types of solutions at a national Canadian level. METHODS: A mixed-methods study involving an online survey and focus groups (FGs) was conducted among AYAs residing in different regions of Canada. RESULTS: There were a total of 174 survey respondents, of whom the majority were between 30-39 years of age (n = 125, 71.8%). Of the 174 respondents, 36 (20.7%) participated in one of seven FGs. Triangulation of the results illustrated that AYAs are not appropriately informed about the long-term health risks of being treated for cancer and where/how to seek support. These results culminated into three themes: (1) the need for AYA relevant and timely information about health risks; by (a) producing health risk-related content with the AYA life stage in mind; (b) providing a guided "map" to help AYAs anticipate what they may experience, and (c) providing checklists to help AYAs navigate their experience; (2) need for tailored and timely supportive care including (a) establishing ongoing check-ins and (b) receiving navigation support, and (3) need for enhanced connections by creating (a) a space to gather, connect and seek mentorship and (b) a hub to access information. CONCLUSION: AYAs continue to lack sufficient support both during and following cancer and mechanisms are required to ensure longitudinal support is provided across jurisdictions and in all stages of the cancer journey.

Implementation of the Canadian National Standards in Breast Cancer Surgical Care: Gaps, Barriers, Enablers and Opportunities.

Background: Diagnosis and surgical treatment decision making for breast cancers has become increasingly complex. Recently, Canadian Partnership Against Cancer (CPAC) published pan-Canadian evidence-based surgical standards for the care of breast cancer patients. This study was undertaken to assess the degree to which these standards were currently met in practice and to further understand the determinants of their implementation nationally. Methods: This study was undertaken in two parts-(1) National survey of breast cancer surgeons to assess the perceived extent of implementation of these standards in their institution and province; (2) Formation of a focus group with a representative sample of breast surgeons across Canada to further understand the barriers and facilitators towards future breast standards implementation. Results: 35 surgeons participated in the survey: 66% were from community hospitals. There were four categories of standards that were the most significantly lacking across the country-(a) processes related to quality assurance, (b) turnaround time for pathology results (c) psychosocial and health-related support for the breast cancer patient and (d) breast reconstruction for patients undergoing mastectomy. The focus group included participants from all ten Canadian provinces. For each standard, the 134 determinants fell into three main categories-individual physician (n = 27, 20%); organizational (n = 46, 34%), and system (n = 61, 46%). While specific determinants were present for each category, surgical standards were more likely to be implemented in practice if (1) they aligned with organizational priorities standards; (2) the individual physicians or physician groups were accountable to the organization and/or cancer jurisdiction regarding compliance with the standard; and (3) if infrastructure or resources existed within the organization or system for the reliable collection of relevant, meaningful, practice changing data combined with the capability of benchmarking, peer-peer comparisons and timely feedback to the surgeons. Conclusion: The results of this study demonstrated variation, barriers and opportunities for the national implementation of CPAC's breast cancer surgery standards and identified determinants of high-quality breast surgical care delivery.

National Thoracic Surgery Standards Implementation: Barriers, Enablers, and Opportunities.

BACKGROUND: Diagnosis and surgical treatment decision making for thoracic cancers is complex. Moreover, there is demonstrated variability in how each province in Canada delivers cancer care, resulting in disparities in patient outcomes. Recently, the Canadian Partnership Against Cancer (CPAC) published pan-Canadian evidence-based standards for the care of thoracic surgery cancer patients. This study was undertaken to assess the degree to which these standards were currently met in practice and to further understand the determinants to their implementation nationally. METHODS: This study was undertaken in two parts: (1) a national survey of thoracic surgeons to assess the perceived extent of implementation of these standards in their institution and province; and (2) formation of a focus group with a representative sample of thoracic surgeons across Canada in a qualitative study to understand the determinants of successful standards implementation. RESULTS: 37 surgeons (33% response rate) participated in the survey; 78% were from academic hospitals. The top categories of standards that were under-implemented included (a) quality assurance processes, data collection and clinician audit and feedback, and (b) ongoing regional planning and workload assessments for thoracic surgeons, and (c) pathology turnaround time target of two weeks and the use of a standardized synoptic pathology report format. Enablers, barriers, and opportunities for standards implementation contextualized the discussion within the focus group. CONCLUSION: Study results demonstrated variation in the implementation of surgery standards across Canada and identified the determinants to the delivery of high quality surgical care. Future work will need to include the promotion and development of quality improvement strategies and effective resource allocation that is aligned with the implementation of thoracic cancer surgery standards in order to improve patient outcomes.

Sustaining knowledge translation interventions for chronic disease management in older adults: protocol for a systematic review and network meta-analysis.

BACKGROUND: Failure to sustain knowledge translation (KT) interventions impacts patients and health systems, diminishing confidence in future implementation. Sustaining KT interventions used to implement chronic disease management (CDM) interventions is of critical importance given the proportion of older adults with chronic diseases and their need for ongoing care. Our objectives are to (1) complete a systematic review and network meta-analysis of the effectiveness and cost-effectiveness of sustainability of KT interventions that target CDM for end-users including older patients, clinicians, public health officials, health services managers and policy-makers on health care outcomes beyond 1 year after implementation or the termination of initial project funding and (2) use the results of this review to complete an economic analysis of the interventions identified to be effective. METHODS: For objective 1, comprehensive searches of relevant electronic databases (e.g. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials), websites of health care provider organisations and funding agencies will be conducted. We will include randomised controlled trials (RCTs) examining the impact of a KT intervention targeting CDM in adults aged 65 years and older. To examine cost, economic studies (e.g. cost, cost-effectiveness analyses) will be included. Our primary outcome will be the sustainability of the delivery of the KT intervention beyond 1 year after implementation or termination of study funding. Secondary outcomes will include behaviour changes at the level of the patient (e.g. symptom management) and clinician (e.g. physician test ordering) and health system (e.g. cost, hospital admissions). Article screening, data abstraction and risk of bias assessment will be completed independently by two reviewers. Using established methods, if the assumption of transitivity is valid and the evidence forms a connected network, Bayesian random-effects pairwise and network meta-analysis will be conducted. For objective 2, we will build a decision analytic model comparing effective interventions to estimate an incremental cost-effectiveness ratio. DISCUSSION: Our results will inform knowledge users (e.g. patients, clinicians, policy-makers) regarding the sustainability of KT interventions for CDM. Dissemination plan of our results will be tailored to end-users and include passive (e.g. publications, website posting) and interactive (e.g. knowledge exchange events with stakeholders) strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018084810.

The perception of medical professionals and medical students on the usefulness of an emergency medical card and a continuity of care report in enhancing continuity of care.

OBJECTIVES: To evaluate the medical professionals and medical students perceived usefulness of an emergency medical card (EMC) and a continuity of care (CoC) report, in enhancing CoC. METHODS: The study reviewers included medical professionals from outpatient clinics at Intermountain Healthcare and fourth-year medical students from the University of Utah. Three cases we randomly extracted from a database of patients who had added new care information at the time. EMCs and CoC reports were populated for the cases, and information then de-identified. Using patient information in the electronic medical record (EMR), reviewers evaluated if the EMR information was adequate to support medical decisions made on the patient's diagnosis, medications, laboratory tests, and disposition. The reviewer assessed if the EMC and CoC report information would influence the medical decisions made. An online survey was used to assess the reviewers' perception on the usefulness of the two documents. RESULTS: On average, 94% of the reviewers perceived the EMC to be useful in enhancing medical decision making at the point of care, and 74% found the CoC report to be useful. More specifically, the two documents were found to be useful in decreasing encounter time (100% each), increasing overall knowledge of healthcare providers (100% each), influencing decision on the treatment (94% each), and new laboratory test orders (87% and 90%, respectively). CONCLUSIONS: The EMC and CoC report were found to be useful methods for transporting patient healthcare information across the healthcare continuum. The documents were found more specifically to be useful for effective decision making, improving efficiency and quality of care, at the point of care.