Additional file 1 of Aligning organisational priorities and implementation science for cancer research

Supplementary Material 1

Development of a tailored, computerized, breast cancer risk assessment and decision support tool: What do clinicians want?

Development of a tailored, computerized, breast cancer risk assessment and decision support tool: What do clinicians want

Development of a tailored, computerized, breast cancer risk assessment and decision support tool: What do clinicians want?

e20660 Background: End user input into the design of decision support tools is critical to enhance integration and future routine use in clinical practice. As part of the development of an evidence-based, tailored, computerized breast cancer (BC) risk assessment and management tool, we examined clinicians’ requirements. Methods: Australian breast surgeons (BSs) and primary care clinicians (PCCs) were recruited through local professional networks. Facilitated focus group discussions about current practice of assessing and managing BC risk and perceptions of the proposed tool were audiotaped transcribed and managed using QSR NVivo. A coding framework was developed based on the transcripts, data were coded and each code further analyzed to identify key themes. Results: Four focus groups, involving 12 BSs, 17 PCCs (12 doctors, 5 practice nurses) were conducted. 55 % were male, mean age 45yrs (range 25-67), mean of 14yrs in practice (range1-25+). Clinicians identified difficulties assessing and managing BC risk and lack of available tools to standardise their current inconsistent approach to risk assessment and management. Most felt confident identifying high risk women, but found differentiating women at population risk from those at moderately increased risk more difficult. They felt a tool would help them reassure anxious low to moderate risk women and avoid unnecessary onward referral or investigations and better identify and refer or manage high risk women. Desirable features in a tool included: evidence-based, accessible (web-based), visual, simple data entry process, displays absolute risk (rather than relative) and mutable risk and risk reduction estimates in multiple formats (words, pictographs, graphs) to improve comprehension, printable summary sheets. Clinicians felt that women could input risk factors before the clinic visit but that joint consumer and clinician data entry was preferable and women should only receive a risk estimate with a clinician present. Conclusions: Development of tools for BC risk assessment and management should address these clearly identified needs of end users in order to optimise translation of current and future knowledge into clinical practice

Assessing breast cancer risk in primary care: What can we learn from cardiovascular disease?

1559 Background: Routine assessment of breast cancer (BC) risk by primary care clinicians (PCCs) might improve uptake of BC prevention and screening interventions, thus reducing morbidity and mortality as has occurred for cardiovascular (CV) disease. Methods: Australian PCCs were recruited through local professional networks. Facilitated focus group discussions about current practice of assessing and managing BC risk were audiotaped, transcribed verbatim and managed using QSR NVivo qualitative data management software. A coding framework was developed based on the transcripts, data were coded and each code further analyzed to identify key themes. Results: 17 PCCs (12 doctors, 5 practice nurses) participated in 2 focus groups. 41% were male, median age 49 years, median number of years in practice was 15. Approaches to assessment and management of BC risk differed markedly from that of CV risk. PCCs see assessment and management of CV risk as an intrinsic, expected part of their role. Practice software prompts trigger CV risk assessment and PCCs often use an online tool (www.knowyournumbers.co.nz) to provide personalized risk estimates and to discuss management options for CV risk. Conversely, assessment of BC risk is not routine or prompted by practice software, is generally patient (not clinician) initiated, and management, beyond routine BC screening (e.g. chemoprevention), is considered outside the PCCs domain. Most PCCs are not familiar with, or using, BC risk assessment tools. PCCs suggested they could potentially routinely assess and manage BC risk. Such an approach would need to be widely endorsed as within the remit of primary care and would be enhanced by an online tool that is accessible, quick, visual (graphs and pictograms), evidence-based and regularly updated. Ideally, its use would be prompted by their practice software. Conclusions: There is a clear opportunity in primary care to enhance the capacity and motivation of clinicians to assess and manage BC risk. A risk assessment and decision aid tool, integrated into primary care software, might facilitate routine appropriate management of BC risk in the Australian primary care setting, modelling what has already been achieved for CV disease

Additional file 1: of Prevalence of PALB2 mutations in Australian familial breast cancer cases and controls

Cohort information (Table). (DOCX 48 kb

Additional file 2: of Prevalence of PALB2 mutations in Australian familial breast cancer cases and controls

PALB2 truncating variant carrier family pedigrees (Figure). (PDF 1036 kb

Presentation_1_Case Report: Hypoglycemia Due to a Novel Activating Glucokinase Variant in an Adult – a Molecular Approach.pptx

We present a case of an obese 22-year-old man with activating GCK variant who had neonatal hypoglycemia, re-emerging with hypoglycemia later in life. We investigated him for asymptomatic hypoglycemia with a family history of hypoglycemia. Genetic testing yielded a novel GCK missense class 3 variant that was subsequently found in his mother, sister and nephew and reclassified as a class 4 likely pathogenic variant. Glucokinase enables phosphorylation of glucose, the rate-limiting step of glycolysis in the liver and pancreatic β cells. It plays a crucial role in the regulation of insulin secretion. Inactivating variants in GCK cause hyperglycemia and activating variants cause hypoglycemia. Spleen-preserving distal pancreatectomy revealed diffuse hyperplastic islets, nuclear pleomorphism and periductular islets. Glucose stimulated insulin secretion revealed increased insulin secretion in response to glucose. Cytoplasmic calcium, which triggers exocytosis of insulin-containing granules, revealed normal basal but increased glucose-stimulated level. Unbiased gene expression analysis using 10X single cell sequencing revealed upregulated INS and CKB genes and downregulated DLK1 and NPY genes in β-cells. Further studies are required to see if alteration in expression of these genes plays a role in the metabolic and histological phenotype associated with glucokinase pathogenic variant. There were more large islets in the patient’s pancreas than in control subjects but there was no difference in the proportion of β cells in the islets. His hypoglycemia was persistent after pancreatectomy, was refractory to diazoxide and improved with pasireotide. This case highlights the variable phenotype of GCK mutations. In-depth molecular analyses in the islets have revealed possible mechanisms for hyperplastic islets and insulin hypersecretion.</p