Kate A McBride

Li-Fraumeni syndrome: cancer risk assessment and clinical management

Carriers of germline mutations in the TP53 gene, encoding the cell-cycle regulator and tumour suppressor p53, have a markedly increased risk of cancer-related morbidity and mortality during both childhood and adulthood, and thus require appropriate and effective cancer risk management. However, the predisposition of such patients to multiorgan tumorigenesis presents a specific challenge for cancer risk management programmes. Herein, we review the clinical implications of germline mutations in TP53 and the evidence for cancer screening and prevention strategies in individuals carrying such mutations, as well as examining the potential psychosocial implications of lifelong management for a ubiquitous cancer risk. In addition, we propose an evidence-based framework for the clinical management of TP53 mutation carriers and provide a platform for addressing the management of other cancer predisposition syndromes that can affect multiple organs.

Development of a human papillomavirus vaccination intervention for Australian adolescents

Objective: Australia has implemented a nation-wide programme providing a human papillomavirus (HPV) vaccine to girls and boys through school-based programmes. Previous research has identified three distinct areas for attention: (1) lack of understanding about HPV and HPV vaccination, (2) young people’s desire for involvement in decision-making about HPV vaccination and (3) fear of HPV vaccination. We aimed to develop an intervention to address young people’s low levels of understanding, to promote their involvement in consent and reduce vaccination-related fear and anxiety. Design, Setting, Methods: Formative qualitative research was conducted in six public, private and Catholic schools in the Sydney metropolitan area. Girls who were offered the vaccine in a school programme and aged 12–13u2009years were interviewed in focus groups. Piloting of materials was conducted in three private schools across Sydney with both girls and boys, and changes and additions were made to the materials in accordance with feedback. Results: We developed an educational intervention aimed at addressing gaps in young people’s knowledge and understanding, and offering strategies to improve confidence with vaccination and reduce needle-related anxiety. Components of the final intervention include film chapters, a magazine, a website, an app and teacher support materials. The intervention is designed for teachers and/or nurses to deliver and is linked to the school-based HPV vaccination programme. Conclusions: This is the first educational intervention designed for young people in HPV school-based vaccination, to be developed from empirical data with the involvement of young people themselves.

Psychosocial morbidity in TP53 mutation carriers: is whole-body cancer screening beneficial?

Germline TP53 mutation carriers are at high risk of developing a range of cancers. Effective cancer risk management is an important issue for these individuals. We assessed the psychosocial impact in TP53 mutation carriers of WB-MRI screening as part of the Surveillance in Multi-Organ Cancer (SMOC+) protocol, measuring their unmet needs, anxiety and depression levels as well as cancer worry using psychological questionnaires and in-depth interviews about their experiences of screening. We present preliminary psychosocial findings from 17 participants during their first 12xa0months on the trial. We found a significant reduction in participants’ mean anxiety from baseline to two weeks post WB-MRI (1.2, 95% CI 0.17 to 2.23 pu2009=u20090.025), indicative of some benefit. Emerging qualitative themes show most participants are emotionally supported and contained by the screening program and are motivated by their immediate concern about staying alive, despite being informed about the current lack of evidence around efficacy of screening for people with TP53 mutations in terms of cancer morbidity or mortality. For those that do gain emotional reassurance from participating in the screening study, feelings of abandonment by the research team are a risk when the study ends. For others, screening was seen as a burden, consistent with the relentless nature of cancer risk associated with Li-Fraumeni syndrome, though these patients still declared they wished to participate due to their concern with staying alive. Families with TP53 mutations need ongoing support due to the impact on the whole family system. These findings suggest a comprehensive multi-organ screening program for people with TP53 mutations provides psychological benefit independent of an impact on cancer morbidity and mortality associated with the syndrome. The benefits of a multi-organ screening program will be greater still if the screening tests additionally reduce the cancer morbidity and mortality associated with the syndrome. These findings may also inform the care of individuals and families with other multi-organ cancer predisposition syndromes.

Timing and context : important considerations in the return of genetic results to research participants

General consensus exists that clinically significant germline genetic research results should be fed back to research participants. A body of literature is emerging about Australian research participants’ experiences of feedback of genetic research results and factors that influence a participant’s actions after receiving such information. This exploratory qualitative study conducted interviews with 11 participants from the International Sarcoma Kindred Study, four probands and seven of their relatives. They had been informed by letter of the availability of clinically significant germline TP53 mutations identified through research. We examined the participants’ views about the feedback of these genetic test results. Thematic (inductive) analysis was used to analyse the data. A number of factors influenced participants’ responses following notification. This included participants’ understanding of the notification letter and their perception of the relevance of the information for them and/or their family. Most notably, timing of the letter in the context of an individual’s current life experiences was important. Timing and context are novel factors identified that may impact on research participants’ understanding or their ability to access clinically significant research results. We outline strategies for disseminating results to research participants and their next of kin that may reduce their uncertainty around the receipt of research results.

A systematic review of health promotion intervention studies in the police force: study characteristics, intervention design and impacts on health

To systematically review studies of health promotion intervention in the police force. Four databases were searched for articles reporting on prepost single and multigroup studies in police officers and trainees. Data were extracted and bias assessed to evaluate study characteristics, intervention design and the impact of interventions on health. Database searching identified 25 articles reporting on 21 studies relevant to the aims of this review. Few studies (n=3) were of long duration (≥6 months). Nine of 21 studies evaluated structured physical activity and/or diet programmes only, 5 studies used education and behaviour change support-only interventions, 5 combined structured programmes with education and behaviour change support, and 2 studies used computer prompts to minimise sedentary behaviour. A wide array of lifestyle behaviour and health outcomes was measured, with 11/13 multigroup and 8/8 single-group studies reporting beneficial impacts on outcomes. High risk of bias was evident across most studies. In those with the lowest risk of bias (n=2), a large effect on blood pressure and small effects on diet, sleep quality, stress and tobacco use, were reported. Health promotion interventions can impact beneficially on health of the police force, particularly blood pressure, diet, sleep, stress and tobacco use. Limited reporting made comparison of findings challenging. Combined structured programmes with education and behaviour change support and programmes including peer support resulted in the most impact on health-related outcomes.

International survey of awareness of genetic risk in the clinical sarcoma community

Integration of clinical genetics into oncology is variable. Sarcomas have a strong genetic component, with up to 1/30 patients carrying germline TP53 mutations. This study aimed to define genetic risk awareness among sarcoma physicians. Outcomes were attitudes toward genetic testing, level of cancer risk and awareness of risk reduction measures.

Lifestyle interventions for people with, and at risk of type 2 diabetes in Polynesian communities : a systematic review and meta-analysis

There is evidence that lifestyle intervention among Polynesian people can reduce diabetes incidence and complications, but this evidence has not been systematically reviewed. The aim of this study was to systematically review the efficacy of lifestyle interventions, targeting the prevention and management of type 2 diabetes among Polynesian people. MEDLINE, Web of Science, Cochrane Library, and Embase were searched to find randomised controlled trials (RCTs) and pre-post studies. Eight studies (four RCTs and four pre-post studies) with 1590 participants met the inclusion criteria. The data on health outcomes that was reported in these studies included blood pressure, body mass index, waist circumference, weight, and glycated haemoglobin (HbA1c). The meta-analyses showed that the interventions had resulted in statistically significant reductions in systolic blood pressure (SBP) across four of the studies (WMD, −9.93 mmHg; 95% Cl, −10.77 to −9.09; and p < 0.00001). However, the effects on weight across five of the studies (WMD, −1.15 kg; 95% Cl, −2.80 to 0.51; p = 0.18) and the HbA1c levels across two of the studies (WMD, −0.38%; 95% Cl, −1.15 to 0.39; and p = 0.33) were not statistically significant. This review provides evidence that lifestyle interventions may be effective in achieving modest reductions in SBP in Polynesian people. Further research is needed to fully assess the effectiveness of these interventions in this population long-term.

Development and validation of measures to evaluate adolescents' knowledge about human papillomavirus (HPV), involvement in HPV vaccine decision-making, self-efficacy to receive the vaccine and fear and anxiety

Objectives We describe the development and validation of measures of human papillomavirus (HPV)/HPV vaccination knowledge, fear/anxiety about vaccination, involvement in HPV vaccine decision-making, and self-efficacy with regard to getting the vaccine, designed to evaluate the efficacy of an intervention to affect these domains (collectively termed the HAVIQ: HPV Adolescent Vaccine Intervention Questionnaire). Study design Literature search, cognitive interviews and cross-sectional survey. Methods A literature search identified existing items that were modified for the present measures. Experts reviewed draft measures for face and content validity. Cognitive interviews with adolescents were also used to assess content validity. Adolescents completed the measures and an internal reliability analysis of each measure was performed. Results The four experts concurred that the measures had face validity. Cognitive interviews identified items requiring refinement. Content validity was examined with ten experts and was deemed acceptable. There were 1800 adolescents who completed the measures; Cronbachs alpha was >0.6 for three of the four measures. The four final measures are brief, comprising 25 items in total. Conclusions The measures are robustly developed and validity-tested. The HAVIQ may be used in research settings to evaluate adolescents knowledge and experiences of the process of HPV vaccination in a school-based vaccination programme.

Health priorities and health-seeking behaviors of Old Order Anabaptists in southern Ontario with emphasis on cancer screening

Background: Cancer-screening rates are low among Old Order Anabaptists; the burden of cancer is unknown. Purpose: To investigate cancer and health in the Old Order Anabaptist context. Specifically, to describe health priorities and health-seeking behaviors, crudely estimate cancer burden, and identify predictors of cancer screening. Method: A cross-sectional survey was distributed to households around Perth County, Ontario, in January 2014. Results: Response rate was 45%. Cancer burden was low. Cancer was a lower priority than general and mental health. After adjustment, family/friends motivated cancer screening for regular screeners (OR: 6.38, 95% CI [1.93, 21.07]) and symptoms was reported to motivate those underscreened/never screened (OR: 0.48, 95% CI [0.24, 0.96]). Conclusion: Cancer-screening participation may be low because the burden of cancer is low and there are other high-priority health concerns. Implications: Integrated cancer screening and holistic care may improve participation.