Challenges, Strengths and Opportunities Related to Implementing Comprehensive Evidence-Based Guidelines on Breast Cancer Survivorship Care by Primary Care Physicians and Nurse Practitioners in Southeastern Ontario

Background Many breast cancer survivors continue to have a broad range of physical and psychosocial problems after breast cancer treatment. As cancer centres move forward with earlier discharge of stable breast cancer survivors to primary care follow-up it is important that comprehensive evidence-based breast cancer survivorship care is implemented to effectively address these needs. Research suggests primary care providers are willing to provide breast cancer survivorship care but many lack the knowledge and confidence to provide evidence-based care. Purpose The overall purpose of this thesis was to determine the challenges, strengths and opportunities related to implementing comprehensive evidence-based breast cancer survivorship guidelines by primary care physicians and nurse practitioners in southeastern Ontario. Methods This mixed-methods research was conducted in three phases: (1) synthesis and appraisal of clinical practice guidelines relevant to provision of breast cancer survivorship care within the primary care practice setting; (2) a brief quantitative survey of primary care providers to determine actual practices related to provision of evidence-based breast cancer survivorship care; and (3) individual interviews with primary care providers about the challenges, strengths and opportunities related to provision of comprehensive evidence-based breast cancer survivorship care. Results and Conclusions In the first phase, a comprehensive clinical practice framework was created to guide provision of breast cancer survivorship care and consisted of a one-page checklist outlining breast cancer survivorship issues relevant to primary care, a three-page summary of key recommendations, and a one-page list of guideline sources. The second phase identified several knowledge and practice gaps, and it was determined that guideline implementation rates were higher for recommendations related to prevention and surveillance aspects of survivorship care and lowest related to screening for and management of long-term effects. The third phase identified three major challenges to providing breast cancer survivorship care: inconsistent educational preparation, provider anxieties, and primary care burden; and three major strengths or opportunities to facilitate implementation of survivorship care guidelines: tools and technology, empowering survivors, and optimizing nursing roles. A better understanding of these challenges, strengths and opportunities will inform development of targeted knowledge translation interventions to provide support and education to primary care providers.

Academic Integrity and Senior Nursing Undergraduate Clinical Practice

Background: Academic integrity (AI) has been defined as the commitment to the values of honesty, trust, fairness, respect, and responsibility with courage in all academic endeavours. The senior years of nursing studies provide an intersection for students to transition to professional roles through student clinical practice. It is essential to understand what predicts senior nursing students’ intention to behave with AI so that efforts can be directed to initiatives focused on strengthening their commitment to behaving with AI. Research Questions: To what extent do students differ on Theory of Planned Behaviour (TPB) variables? What predicts intention to behave with academic integrity among senior nursing students in clinical practice across three different Canadian Schools of Nursing? Method: The TPB framework, an elicitation (n=30) and two pilot studies (n=59, n=29) resulted in the development of a 38 question (41-item) self-report survey (Miron Academic Integrity Nursing Survey—MAINS: α>0.70) that was administered to Year 3 and 4 students (N=339). Three predictor variables (attitude, subjective norm, perceived behavioural control) were measured with students’ intention to behave with AI in clinical. Age, sex, year of study, program stream, students’ understanding of AI policies, and locations where students accessed AI information were also measured. Results: Hierarchical multiple regression analyses revealed that background, site, and TPB variables explained 32.6% of the variance in intention to behave with academic integrity. The TPB variables explained 26.8% of the variance in intention after controlling for background and site variables. In the final model, only the TPB predictor variables were statistically significant with Attitude having the highest beta value (beta=0.35, p<0.001), followed by Subjective Norm (beta=0.21, p<0.001) and Perceived Behavioural Control (beta=0.12, p<0.02). Conclusion: Student attitude is the strongest predictor to intention to behave with AI in clinical practice and efforts to positively influence students’ attitudes need to be a focus for schools, curricula, and clinical educators. Opportunities for future research should include replicating the current study with students enrolled in other professional programs and intervention studies that examine the effectiveness of specific endeavours to promote AI in practice.

A structural basis for different antifreeze protein roles

Antifreeze proteins (AFPs) are produced by a variety of organisms to either protect them from freezing or help them tolerate being frozen. Recent structural work has shown that AFPs bind to ice using ordered surface waters on a particular surface of the protein called the ice-binding site (IBS). These 'anchored clathrate' waters fuse to particular planes of an ice crystal and hence irreversibly bind the AFP to its ligand. An AFP isolated from the perennial ryegrass, Lolium perenne (LpAFP) was previously modelled as a right-handed beta helix with two proposed IBSs. Steric mutagenesis, where small side chains were replaced with larger ones, determined that only one of the putative IBSs was responsible for binding ice. The mutagenesis work also partly validated the fold of the computer-generated model of this AFP. In order to determine the structure of the protein, LpAFP was crystallized and solved to 1.4 Å resolution. The protein folds as an untwisted left-handed beta-helix, of opposite handedness to the model. The IBS identified by mutagenesis is remarkably flat, but less regular than the IBS of most other AFPs. Furthermore, several of the residues constituting the IBS are in multiple conformations. This irregularity may explain why LpAFP causes less thermal hysteresis than many other AFPs. Its imperfect IBS is also argued to be responsible for LpAFP's heightened ice-recrystallization inhibition activity. The structure of LpAFP is the first for a plant AFP and for a protein responsible for providing freeze tolerance rather than freeze resistance. To help understand what constitutes an IBS, a non-ice-binding homologue of type III AFP, sialic acid synthase (SAS), was engineered for ice binding. Point mutations were made to the germinal IBS of SAS to mimic key features seen in type III AFP. The crystal structures of some of the mutant proteins showed that the potential IBS became less charged and flatter as the mutations progressed, and ice affinity was gained. This proof-of-principle study highlights some of the difficulties in AFP engineering.