Development and implementation of a remote monitoring and coaching intervention delivered using digital health technology for people with a history of cancer.

There is a need to improve care practices to optimally enhance physical health and health- related quality of life in people with a history of cancer. Intensive treatment of cancer can impact patients both acutely and chronically as long-term or late effects well after treatment completion. As a result, both patients with cancer and cancer survivors need additional support Supportive cancer care, including survivorship and rehabilitation services focuses on developing strategies to support survivors’ well-being and recovery during and after cancer treatment. However, despite the evidence-based benefits of these services, many barriers still exist that may restrict patients with cancer from participation and engagement. One possible solution to these challenges is the use of digital health technologies. The aim of this research was to explore current gaps in knowledge regarding digital health enabled supportive cancer care and design and develop a digital health enabled intervention, specifically tailored to the needs of people with a cancer diagnosis. The experience culminated in the implementation of a 10-week prospective cohort trial, focused on the feasibility and acceptability of a patient-provider tracking and exercise coaching portal. As evidenced by the research studies presented within this thesis, findings suggest that patient-centric supportive care can be provided to cancer patients using a digital health enabled approach. Further, remote monitoring and individual exercise coaching can feasibly be offered to patient populations who may not be able to conveniently access support services, or who choose to access these services remotely. Several recommendations for future research and future directions were provided to further this area of research

The importance of setting and therapeutic relationships when delivering chiropractic care to those living with disadvantage

Background: Chiropractic is a mostly privatised health profession within Australia, with people experiencing disadvantage typically having limited access due to financial barriers. However, some universities within Australia offer community outreach clinics where students provide chiropractic care to people living with disadvantage. This demographic experiences higher rates of chronic conditions including musculoskeletal complaints and requires subsidisation to access privatised care. This need also offers opportunity for the chiropractic profession to work within community healthcare teams. A mixed-methods observational study was used to investigate how the unique setting of a student chiropractic community clinic may influence the experience and outcomes of those who attend. Methods: Three patient-reported outcome measures (PROMs) investigated client outcomes: Measure Yourself Medical Outcome Profile (MYMOP); European Five Domain Five Level Quality of Life Questionnaire (EQ-5D-5L); and the Patient Enablement Instrument. The PROMs data were analysed descriptively and inferentially. Interviews were conducted with clients who had received chiropractic care, chiropractic students, clinical supervisors and staff of the centre. Interview data were coded using thematic analysis, and themes were formed using Bronfenbrenner’s socio-ecological systems framework and non-participant observations. Results: Thirty-seven participants completed baseline PROMs and 17 completed follow-ups after four treatments. Seventy-two percent of participants nominated their primary complaint as chronic. Significant change was noted in general health and wellbeing for the MYMOP, pain and disability for the EQ-5D-5L and index scores for the EQ-5D-5L suggested improved health and wellbeing. Most clients experienced higher levels of enablement post treatment. Twelve participants were interviewed (four were clients), with five themes emerging from the interview data. Clients reported their lived experiences impacted their health problems and attending the clinic offered benefits beyond improvement of pain and disability. Conclusions: Interview data suggested that these benefits were due to a combination of therapy, the setting and the relationships formed within that setting. Complementing this, PROM data suggested clients experienced better levels of health and wellbeing and decreased levels of pain and disability. Findings indicated that people who experienced disadvantage may receive broader benefits from attending community centres offering chiropractic care. Services such as chiropractic may be complementary in meeting the healthcare needs of those experiencing disadvantage. © 2022, The Author(s)

Feasibility of an interactive patient portal in oncology : qualitative study

Background: Digital health interventions, such as the use of patient portals, have been shown to offer benefits to a range of patients including those with a diagnosis of cancer. Objective: This study aimed to explore the participant experience and perception of using an interactive Web-based portal for monitoring physical activity, remote symptom reporting, and delivering educational components. Methods: Participants who were currently under treatment or had recently completed intensive treatment for cancer were recruited to three cohorts and invited to join a Web-based portal to enhance their physical activity. Cohort 1 received Web portal access and an activity monitor; cohort 2 had additional summative messaging; and cohort 3 had additional personalized health coaching messaging. Following the 10-week intervention, participants were invited to participate in a semistructured interview. Interview recordings were transcribed and evaluated using qualitative thematic analysis. Results: A total of 17 semistructured interviews were carried out. Participants indicated that using the Web portal was feasible. Personalized messaging improved participant perceptions of the value of the intervention. There was a contrast between cohorts and levels of engagement with increasing health professional contact leading to an increase in engagement. Educational material needs to be tailored to the participants’ cancer treatment status, health literacy, and background. Conclusions: Participants reported an overall positive experience using the Web portal and that personalized messaging positively impacted on their health behaviors. Future studies should focus more on design of interventions, ensuring appropriate tailoring of information and personalization of behavioral support messaging

A rare variant in EZH2 is associated with prostate cancer risk

Prostate cancer (PrCa) is highly heritable, and although rare variants contribute significantly to PrCa risk, few have been identified to date. Herein, whole-genome sequencing was performed in a large PrCa family featuring multiple affected relatives spanning several generations. A rare, predicted splice site EZH2 variant, rs78589034 (G > A), was identified as segregating with disease in all but two individuals in the family, one of whom was affected with lymphoma and bowel cancer and a female relative. This variant was significantly associated with disease risk in combined familial and sporadic PrCa datasets (n = 1551; odds ratio [OR] = 3.55, P = 1.20 × 10−5). Transcriptome analysis was performed on prostate tumour needle biopsies available for two rare variant carriers and two wild-type cases. Although no allele-dependent differences were detected in EZH2 transcripts, a distinct differential gene expression signature was observed when comparing prostate tissue from the rare variant carriers with the wild-type samples. The gene expression signature comprised known downstream targets of EZH2 and included the top-ranked genes, DUSP1, FOS, JUNB and EGR1, which were subsequently validated by qPCR. These data provide evidence that rs78589034 is associated with increased PrCa risk in Tasmanian men and further, that this variant may be associated with perturbed EZH2 function in prostate tissue. Disrupted EZH2 function is a driver of tumourigenesis in several cancers, including prostate, and is of significant interest as a therapeutic target

Impact of the G84E variant on HOXB13 gene and protein expression in formalin-fixed, paraffin-embedded prostate tumours

The HOXB13 G84E variant is associated with risk of prostate cancer (PCa), however the role this variant plays in PCa development is unknown. This study examined 751 cases, 450 relatives and 355 controls to determine the contribution of this variant to PCa risk in Tasmania and investigated HOXB13 gene and protein expression in tumours from nine G84E heterozygote variant and 13 wild-type carriers. Quantitative PCR and immunohistochemistry showed that HOXB13 gene and protein expression did not differ between tumour samples from variant and wild-type carriers. Allele-specific transcription revealed that two of seven G84E carriers transcribed both the variant and wild-type allele, while five carriers transcribed the wild-type allele. Methylation of surrounding CpG sites was lower in the variant compared to the wild-type allele, however overall methylation across the region was very low. Notably, tumour characteristics were less aggressive in the two variant carriers that transcribed the variant allele compared to the five that did not. This study has shown that HOXB13 expression does not differ between tumour tissue of G84E variant carriers and non-carriers. Intriguingly, the G84E variant allele was rarely transcribed in carriers, suggesting that HOXB13 expression may be driven by the wild-type allele in the majority of carriers

Impact of the G84E variant on HOXB13 gene and protein expression in formalin-fixed, paraffin-embedded prostate tumours

The HOXB13 G84E variant is associated with risk of prostate cancer (PCa), however the role this variant plays in PCa development is unknown. This study examined 751 cases, 450 relatives and 355 controls to determine the contribution of this variant to PCa risk in Tasmania and investigated HOXB13 gene and protein expression in tumours from nine G84E heterozygote variant and 13 wild-type carriers. Quantitative PCR and immunohistochemistry showed that HOXB13 gene and protein expression did not differ between tumour samples from variant and wild-type carriers. Allele-specific transcription revealed that two of seven G84E carriers transcribed both the variant and wild-type allele, while five carriers transcribed the wild-type allele. Methylation of surrounding CpG sites was lower in the variant compared to the wild-type allele, however overall methylation across the region was very low. Notably, tumour characteristics were less aggressive in the two variant carriers that transcribed the variant allele compared to the five that did not. This study has shown that HOXB13 expression does not differ between tumour tissue of G84E variant carriers and non-carriers. Intriguingly, the G84E variant allele was rarely transcribed in carriers, suggesting that HOXB13 expression may be driven by the wild-type allele in the majority of carriers

Impact of the G84E variant on HOXB13 gene and protein expression in formalin-fixed, paraffin-embedded prostate tumours

The HOXB13 G84E variant is associated with risk of prostate cancer (PCa), however the role this variant plays in PCa development is unknown. This study examined 751 cases, 450 relatives and 355 controls to determine the contribution of this variant to PCa risk in Tasmania and investigated HOXB13 gene and protein expression in tumours from nine G84E heterozygote variant and 13 wild-type carriers. Quantitative PCR and immunohistochemistry showed that HOXB13 gene and protein expression did not differ between tumour samples from variant and wild-type carriers. Allele-specific transcription revealed that two of seven G84E carriers transcribed both the variant and wild-type allele, while five carriers transcribed the wild-type allele. Methylation of surrounding CpG sites was lower in the variant compared to the wild-type allele, however overall methylation across the region was very low. Notably, tumour characteristics were less aggressive in the two variant carriers that transcribed the variant allele compared to the five that did not. This study has shown that HOXB13 expression does not differ between tumour tissue of G84E variant carriers and non-carriers. Intriguingly, the G84E variant allele was rarely transcribed in carriers, suggesting that HOXB13 expression may be driven by the wild-type allele in the majority of carriers