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Abstract Enhancing the efficacy of immunotherapy in brain metastases (BrM) requires an improved understanding of the immune composition of BrM and how this is affected by radiation and dexamethasone. Our two-arm pilot study (NCT04895592) allocated 26 patients with BrM to either low (Arm A) or high (Arm B) dose peri-operative dexamethasone followed by pre-operative stereotactic radiosurgery (pSRS) and resection (n= 13 per arm). The primary endpoint, a safety analysis at 4 months, was met. The secondary clinical endpoints of overall survival, distant brain failure, leptomeningeal disease and local recurrence at 12-months were 66%, 37.3%, 6%, and 0% respectively and were not significantly different between arms (p= 0.7739, p= 0.3884, p= 0.3469). Immunological data from two large retrospective BrM datasets and confirmed by correlates from both arms of this pSRS prospective trial revealed that BrM CD8 T cells were composed of predominantly PD1+ TCF1+ stem-like and PD1+ TCF1-TIM3+ effector-like cells. Clustering of TCF1+ CD8 T cells with antigen presenting cells in immune niches was prognostic for local control, even without pSRS. Following pSRS, CD8 T cell and immune niche density were transiently reduced compared to untreated BrM, followed by a rebound 6+ days post pSRS with an increased frequency of TCF1- effector-like cells. In sum, pSRS is safe and therapeutically beneficial, and these data provide a framework for how pSRS may be leveraged to maximize intracranial CD8 T cell responses.

Abstract The carboxy-terminus of the spliceosomal protein PRPF8, which regulates the RNA helicase Brr2, is a hotspot for mutations causing retinitis pigmentosa-type 13, with unclear role in human splicing and tissue-specificity mechanism. We used patient induced pluripotent stem cells-derived cells, carrying the heterozygous PRPF8 c.6926 A > C (p.H2309P) mutation to demonstrate retinal-specific endophenotypes comprising photoreceptor loss, apical-basal polarity and ciliary defects. Comprehensive molecular, transcriptomic, and proteomic analyses revealed a role of the PRPF8/Brr2 regulation in 5’-splice site (5’SS) selection by spliceosomes, for which disruption impaired alternative splicing and weak/suboptimal 5’SS selection, and enhanced cryptic splicing, predominantly in ciliary and retinal-specific transcripts. Altered splicing efficiency, nuclear speckles organisation, and PRPF8 interaction with U6 snRNA, caused accumulation of active spliceosomes and poly(A)+ mRNAs in unique splicing clusters located at the nuclear periphery of photoreceptors. Collectively these elucidate the role of PRPF8/Brr2 regulatory mechanisms in splicing and the molecular basis of retinal disease, informing therapeutic approaches.

BackgroundStarting in 2010, the epidermal growth factor receptor (EGFR) kinase inhibitors erlotinib and gefitinib were introduced into routine use in Aotearoa New Zealand (NZ) for treating advanced lung cancer, but their impact in this setting is unknown. ObjectiveThe study described in this protocol aims to understand the effectiveness and safety of these new personalized lung cancer treatments and the contributions made by concomitant medicines and other factors to adverse outcomes in the general NZ patient population. A substudy aimed to validate national electronic health databases as the data source and the methods for determining patient eligibility and identifying outcomes and variables. MethodsThis study will include all NZ patients with advanced EGFR mutation–positive lung cancer who were first dispensed erlotinib or gefitinib before October 1, 2020, and followed until death or for at least 1 year. Routinely collected health administrative and clinical data will be collated from national electronic cancer registration, hospital discharge, mortality registration, and pharmaceutical dispensing databases by deterministic data linkage using National Health Index numbers. The primary effectiveness and safety outcomes will be time to treatment discontinuation and serious adverse events, respectively. The primary variable will be high-risk concomitant medicines use with erlotinib or gefitinib. For the validation substudy (n=100), data from clinical records were compared to those from national electronic health databases and analyzed by agreement analysis for categorical data and by paired 2-tailed t tests for numerical data. ResultsIn the validation substudy, national electronic health databases and clinical records agreed in determining patient eligibility and for identifying serious adverse events, high-risk concomitant medicines use, and other categorical data with overall agreement and κ statistic of >90% and >0.8000, respectively; for example, for the determination of patient eligibility, the comparison of proxy and standard eligibility criteria applied to national electronic health databases and clinical records, respectively, showed overall agreement and κ statistic of 96% and 0.8936, respectively. Dates for estimating time to treatment discontinuation and other numerical variables and outcomes showed small differences, mostly with nonsignificant P values and 95% CIs overlapping with zero difference; for example, for the dates of the first dispensing of erlotinib or gefitinib, national electronic health databases and clinical records differed on average by approximately 4 days with a nonsignificant P value of .33 and 95% CIs overlapping with zero difference. As of May 2024, the main study is ongoing. ConclusionsA protocol is presented for a national whole-of-patient-population retrospective cohort study designed to describe the safety and effectiveness of erlotinib and gefitinib during their first decade of routine use in NZ for treating EGFR mutation–positive lung cancer. The validation substudy demonstrated the feasibility and validity of using national electronic health databases and the methods for determining patient eligibility and identifying the study outcomes and variables proposed in the study protocol. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12615000998549; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368928 International Registered Report Identifier (IRRID)DERR1-10.2196/51381

Paediatric sleep diagnostics is performed using complex multichannel tests in specialised centres, limiting access and availability and resulting in delayed diagnosis and management. Such investigations are often challenging due to patient size (prematurity), tolerability, and compliance with “gold standard” equipment. Children with sensory/behavioural issues, at increased risk of sleep disordered breathing (SDB), often find standard diagnostic equipment difficult. SDB can have implications for a child both in terms of physical health and neurocognitive development. Potential sequelae of untreated SDB includes failure to thrive, cardiopulmonary disease, impaired learning and behavioural issues. Prompt and accurate diagnosis of SDB is important to facilitate early intervention and improve outcomes. The current gold-standard diagnostic test for SDB is polysomnography (PSG), which is expensive, requiring the interpretation of a highly specialised physiologist. PSG is not feasible in low-income countries or outwith specialist sleep centres. During the coronavirus disease 2019 pandemic, efforts were made to improve remote monitoring and diagnostics in paediatric sleep medicine, resulting in a paradigm shift in SDB technology with a focus on automated diagnosis harnessing artificial intelligence (AI). AI enables interrogation of large datasets, setting the scene for an era of “sleep-omics”, characterising the endotypic and phenotypic bedrock of SDB by drawing on genetic, lifestyle and demographic information. The National Institute for Health and Care Excellence recently announced a programme for the development of automated home-testing devices for SDB. Scorer-independent scalable diagnostic approaches for paediatric SDB have potential to improve diagnostic accuracy, accessibility and patient tolerability; reduce health inequalities; and yield downstream economic and environmental benefits.

Summary: Background: This study evaluates whether there are ethnic differences in time to surgery in women with early-stage (1–3a) breast cancer in four NZ urban regions between 2000 and 2020 pre- and post- Faster Cancer Treatment (FCT) implementation, which was introduced to address inequities in cancer outcomes. Methods: This retrospective analysis used Te Rēhita Mate Ūtaetae (Breast Cancer Foundation National Register), a prospectively maintained database of breast cancers from 2000 to 2020. Women with stage 3b, 3c, metastatic or bilateral cancers were excluded. Logistic regression models evaluated ethnic differences in time to surgery (≤31/>31 days as per FCT plan) with sequential adjustment for potential contributing factors (demographic, mode of diagnosis, tumour, treatment facility type and treatment). Subgroup analyses by pre- and post-FCT implementation date were undertaken. Findings: Of the 16,365 women included, 74.1% were NZ European (NZE), 10.2% were Māori, 6.1% were Pacific, and 9.2% were Asian. Wāhine Māori (Māori women) and Pacific women were more likely to experience delays in surgery >31 days, compared to NZE (maximally adjusted OR: 1.18; 95% CI:1.05, 1.33 and OR:1.42; 95% CI:1.22, 1.65, respectively)–deprivation and treatment facility type contributed most to this. Wāhine Māori experienced delay in the public system only. The associations did not differ between the pre- and post- FCT periods. Interpretation: Ethnic inequities exist with respect to time to surgery for women with early-stage breast cancer and these differences persist after FCT implementation. Funding: LB is supported by the Richard Stewart scholarship, the Royal Australasian College of Surgeons and Oxford Population Health.

Background Virtual care may improve access to healthcare and may be well suited to digitally connected youth, but experts caution that privacy and technology barriers could perpetuate access inequities. Success of virtual care will depend on its alignment with patient preferences. However, information on preferences for virtual and in-person healthcare is missing, especially for youth. We sought to quantify preferences for and barriers to virtual versus in-person mental and physical healthcare in youth and their parents, including in vulnerable segments of the population such as families with a parent with severe mental illness (SMI).Methods Participants were 219 youth and 326 parents from the Families Overcoming Risks and Building Opportunities for Wellbeing cohort from Canada, of which 61% of youth had at least one parent with SMI. Participants were interviewed about healthcare preferences and access to privacy/technology between October 2021 and December 2022.Results Overall, youth reported a preference for in-person mental (66.6%) and physical healthcare (74.7%) versus virtual care or no preference, and to a somewhat lesser degree, so did their parents (48.0% and 53.9%). Half of participants reported privacy/technology barriers to virtual care, with privacy being the most common barrier. Preferences and barriers varied as a function of parent SMI status, socioeconomic status and rural residence.Conclusions The majority of youth and parents in this study prefer in-person healthcare, and the preference is stronger in youth and in vulnerable segments of the population. Lack of privacy may be a greater barrier to virtual care than access to technology.

Abstract Objectives The objective of this study is to investigate the influence of diabetes on breast cancer‐specific survival among women with breast cancer in Aotearoa/New Zealand. Methods This study included women diagnosed with invasive breast cancer between 2005 and 2020, with their information documented in the Te Rēhita Mate Ūtaetae—Breast Cancer Foundation National Register. Breast cancer survival curves for women with diabetes and those without diabetes were generated using the Kaplan–Meier method. The hazard ratio (HR) of breast cancer‐specific mortality for women with diabetes compared to women without diabetes was estimated using the Cox proportional hazards model. Results For women with diabetes, the 5‐year and 10‐year of cancer‐specific survival were 87% (95% CI: 85%–88%) and 79% (95% CI: 76%–81%) compared to 89% (95% CI: 89%–90%) and 84% (95% CI: 83%–85%) for women without diabetes. The HR of cancer‐specific mortality for patients with diabetes compared to those without diabetes was 0.99 (95% CI: 0.89–1.11) after adjustment for patient demographics, tumor characteristics, and treatments. Age at cancer diagnosis and cancer stage had the biggest impact on the survival difference between the two groups. When stratified by cancer stage, the cancer‐specific mortality between the two groups was similar. Conclusions While differences in survival have been identified for women with diabetes when compared to women without diabetes, these are attributable to age and the finding that women with diabetes tend to present with more advanced disease at diagnosis. We did not find any difference in survival between the two groups due to differences in treatment.

IntroductionSurgical site infections (SSI) are the most common healthcare-associated infections; however, access to healthcare services, lack of patient awareness of signs, and inadequate wound surveillance can limit timely diagnosis. Telemedicine as a method for remote postoperative follow-up has been shown to improve healthcare efficiency without compromising clinical outcomes. Furthermore, telemedicine would reduce the carbon footprint of the National Health Service (NHS) through minimising patient travel, a significant contributor of carbon dioxide equivalent (CO2e) emissions. Adopting innovative approaches, such as telemedicine, could aid in the NHS Net-Zero target by 2045. This study aimed to provide a comprehensive analysis of the feasibility and sustainability of telemedicine postoperative follow-up for remote diagnosis of SSI.MethodsPatients who underwent a lower limb vascular procedure were reviewed remotely at 30 days following the surgery, with a combined outcome measure (photographs and Bluebelle Wound Healing Questionnaire). A hybrid life-cycle assessment approach to carbon footprint analysis was used. The kilograms of carbon dioxide equivalent (kgCO2e) associated with remote methods were mapped prospectively. A simple outpatient clinic review, i.e., no further investigations or management required, was modelled for comparison. The Department of Environment, Food, and Rural Affairs (DEFRA) conversion factors plus healthcare specific sources were used to ascertain kgCO2e. Patient postcodes were applied to conversion factors based upon mode of travel to calculate kgCO2e for patient travel. Total and median (interquartile range) carbon emissions saved were presented for both patients with and without SSI.ResultsAltogether 31 patients (M:F 2.4, ±11.7 years) were included. The median return distance for patient travel was 42.5 (7.2–58.7) km. Median reduction in emissions using remote follow-up was 41.2 (24.5–80.3) kgCO2e per patient (P

Abstract The sound of a person’s voice is commonly used to identify the speaker. The sound of speech is also starting to be used to detect medical conditions, such as depression. It is not known whether the manifestations of depression in speech overlap with those used to identify the speaker. In this paper, we test the hypothesis that the representations of personal identity in speech, known as speaker embeddings, improve the detection of depression and estimation of depressive symptoms severity. We further examine whether changes in depression severity interfere with the recognition of speaker’s identity. We extract speaker embeddings from models pre-trained on a large sample of speakers from the general population without information on depression diagnosis. We test these speaker embeddings for severity estimation in independent datasets consisting of clinical interviews (DAIC-WOZ), spontaneous speech (VocalMind), and longitudinal data (VocalMind). We also use the severity estimates to predict presence of depression. Speaker embeddings, combined with established acoustic features (OpenSMILE), predicted severity with root mean square error (RMSE) values of 6.01 and 6.28 in DAIC-WOZ and VocalMind datasets, respectively, lower than acoustic features alone or speaker embeddings alone. When used to detect depression, speaker embeddings showed higher balanced accuracy (BAc) and surpassed previous state-of-the-art performance in depression detection from speech, with BAc values of 66% and 64% in DAIC-WOZ and VocalMind datasets, respectively. Results from a subset of participants with repeated speech samples show that the speaker identification is affected by changes in depression severity. These results suggest that depression overlaps with personal identity in the acoustic space. While speaker embeddings improve depression detection and severity estimation, deterioration or improvement in mood may interfere with speaker verification.

PURPOSELung cancer is the biggest cancer killer of indigenous peoples worldwide, including Māori people in New Zealand. There is some evidence of disparities in access to lung cancer treatment between Māori and non-Māori patients, but an examination of the depth and breadth of these disparities is needed. Here, we use national-level data to examine disparities in access to surgery, radiation therapy and systemic therapy between Māori and European patients, as well as timing of treatment relative to diagnosis.METHODSWe included all lung cancer registrations across New Zealand from 2007 to 2019 (N = 27,869) and compared access with treatment and the timing of treatment using national-level inpatient, outpatient, and pharmaceutical records.RESULTSMāori patients with lung cancer appeared less likely to access surgery than European patients (Māori, 14%; European, 20%; adjusted odds ratio [adj OR], 0.82 [95% CI, 0.73 to 0.92]), including curative surgery (Māori, 10%; European, 16%; adj OR, 0.72 [95% CI, 0.62 to 0.84]). These differences were only partially explained by stage and comorbidity. There were no differences in access to radiation therapy or systemic therapy once adjusted for confounding by age. Although it appeared that there was a longer time from diagnosis to radiation therapy for Māori patients compared with European patients, this difference was small and requires further investigation.CONCLUSIONOur observation of differences in surgery rates between Māori and European patients with lung cancer who were not explained by stage of disease, tumor type, or comorbidity suggests that Māori patients who may be good candidates for surgery are missing out on this treatment to a greater extent than their European counterparts.

BackgroundClimate change is an era-defining health concern, with healthcare related emissions paradoxically compounding negative impacts. The NHS produces 5% of the UK's carbon footprint, with operating theatres a recognised carbon hotspot. NHS England aims to become Net Zero by 2045. Consequently, UK Royal Colleges of Surgery have published guidance to foster an evidence-based sustainable transformation in surgical practice.MethodsA single-centre quality improvement project was undertaken, aiming to provide an overview of sustainable practice locally. The Intercollegiate “Green Theatre Checklist” was taken as an audit standard, focusing on “preparing for surgery” and “intraoperative equipment” subsections. Any general surgical procedure was eligible for inclusion. Usage of reusable textiles, non-sterile gloves, catheters, antibiotics, alcohol vs. water-based scrub techniques, skin sterilisation choices, and skin closure materials were recorded. Baseline data collection occurred over a 3 week period, followed by dissemination of results locally via clinical governance meetings and poster displays. A re-audit of practice was conducted using the same methodology and duration.ResultsDatasets 1 (n = 23) and 2 (n = 23) included open (n = 22), laparoscopic (n = 24), elective (n = 22) and non-elective (n = 24) cases. Good practice was demonstrated in reusable textiles (trolley covers 96%, 78%, drapes 100%, 92%) however procurement issues reduced otherwise good reusable gown use in Dataset 2 in (90%, 46%). No unnecessary catheter use was identified, and loose skin preparations were used unanimously. Uptake of alcohol-based scrubbing techniques was low (15%, 17%) and unnecessary non-sterile glove use was observed in >30% of procedures. All laparoscopic ports and scissors were single use. Carbon footprints were 128.27 kgCO2e and 117.71 kgCO2e in datasets 1 and 2 respectively.ConclusionThis project evidences good practice alongside future local focus areas for improved sustainability. Adoption of hybrid laparoscopic instruments, avoiding unnecessary equipment opening, and standardising reusable materials could reduce carbon and environmental impact considerably. Successful implementation requires considered procurement practices, improved awareness and education, clear leadership, and a sustained cultural shift within the healthcare community. Collaboration among professional institutions and access to supporting evidence is crucial in driving engagement and empowering clinicians to make locally relevant changes a reality.

In light of the disruptions caused by the COVID-19 pandemic, leaders of higher education institutions around the world have been contemplating ways to help their universities engage in a digital transformation that must have student engagement and learning as the foremost considerations. This study reports on the work conducted at a university in Colombia that created an evaluation instrument based on the Academic Communities of Engagement (ACE) framework (Borup et al., 2020) to examine how well the institution was supporting the affective, behavioral, and cognitive (ABC) dimensions of engagement in its online and blended learning course offerings. This survey, the ACE in Higher Education (ACE-HE), measures indicators of the ABC engagement dimensions as well as indicators of institutional support for those elements. The survey was completed by 1,295 university students representing a broad demographic profile. Structural equation modeling found good fit for both the model of ABC engagement dimensions and the model of institutional support for ABC engagement dimensions. Institutional support for affective engagement showed strong relationships to affective, behavioral, and cognitive indicators of engagement, while institutional support for behavioral and cognitive engagement did not have the same outcome. This research provides access to both English and Spanish versions of the ACE-HE instrument. It also highlights ideas for institutions that want to improve their support for student ABC engagement dimensions in online and blended environments. Finally, several implications for making updates to the ACE framework are shared.

Abstract Background Obesity is a complex health issue affecting the quality of life of individuals and contributing to an unsustainable strain on healthcare professionals and national health systems. National policy guidelines indicate that general practice is best suited to deliver obesity healthcare, however, obesity rates continue to rise worldwide indicating interventions are ineffective in this space. The aim of this study was to explore the weight management experiences from patient perspectives. Methods This qualitative study used semi-structured interviews with 16 rural Waikato general practice patients. Interviews were analysed using reflexive thematic analysis. Results Four themes were identified: Inconsistent Information, Significance of Holistic Factors, Obesity Centre Need, and Education. Participants expressed frustration at contradictory health messages, commercial company and ‘expert’ definition distrust, and that ‘holistic’ aspects to health significant to the weight management journey were unable to be addressed in general practice. Conclusion Whilst primary care is positioned as suitable for delivering obesity healthcare, this study found that participants do not perceive general practice to be equipped to deliver this care. Instead, participants argued for a specialist obesity centre capable of meeting all their obesity healthcare needs. Further, wider issues including on-line commodification of health and neo-liberal capitalism - factors that exploit people with a stigmatised health issue - can cause further harm to the participant. A radical modernisation of education, information, and resources from regulated, qualified and ‘trusted’ healthcare professionals who can provide safe, non-stigmatising supportive services is recommended to meet the unique and changing food climate, reduce obesity rates and improve health outcomes.

Abstract Background Obesity is an international health issue which currently affects over 34% of New Zealand adults and leads to further physical and psychosocial health complications. People living in rural communities experience health inequities and have a high-risk of becoming obese. The aim of this study was to explore and identify barriers to effective weight management in rural Waikato general practice. Methods Using semi-structured interviews, 16 rural Waikato participants shared their experiences with barriers to weight management. Interviews were transcribed and analysed using thematic analysis. Results Four themes were identified: resource constraints, rural locality barriers, rural sociocultural norms barriers, and participants’ understanding the solutions needed to overcome their specific barriers to effective weight management. For these participants, finding a feasible weight management strategy was a challenging first step in their weight management journey. A programme that would ‘work’ meant one that was economically viable for low-income persons, accessible, even if living rurally with less resources, and did not cause harm or jeopardise their social connections within family or community. Conclusion Overall, participants noted a lack of weight management strategy ‘choice’ because of income, isolation or accessibility of their rural location and/or the sociocultural norms of the community they lived in restricted options available to them. Future weight management initiatives may be better devised from within communities themselves and will need to be cognisant of the barriers specific to rural communities. Rural perspectives have much to offer in any such reconsideration of weight management initiatives.

Introduction: Angiocentric gliomas (AG) in brainstem location are exceedingly rare and might cause differential diagnostic problems and uncertainty regarding the best therapeutic approach. Hereby, we describe the clinicopathological findings in a brainstem AG presenting in a toddler child and review the literature.Case report: A 2-year-old boy presented with 5 weeks history of gait disturbances, frequent falls, left-sided torticollis and swallowing problems. MRI head showed a T2-hyperintense, partly exophytic mass lesion centred in the pontomedullary region, raising the possibility of diffuse midline glioma. The exophytic component was partially resected by suboccipital craniotomy, leaving intact the infiltrative component. Ventriculoperitoneal shunt was implanted due to postoperative hydrocephalus. Histological examination revealed a moderately cellular tumour consisted of bland glial cells infiltrating the brain parenchyma and radially arranged around the blood vessels. By immunohistochemistry, the tumour strongly expressed S100 and GFAP in addition to intense nestin positivity, while OLIG2 was negative in the perivascular tumour cells. DNA methylation array profiled the tumour as “methylation class diffuse astrocytoma, MYB or MYBL1-altered subtype B (infratentorial)” and an in-frame MYB::QKI fusion was identified by RNA sequencing, confirming the diagnosis of angiocentric glioma. The patient has been initially treated with angiogenesis inhibitor and mTOR inhibitor, and now he is receiving palliative vinblastine. He is clinically stable on 9 months follow-up.Conclusion: Brainstem AG may cause a diagnostic problem, and the surgical and oncological management is challenging due to unresectability and lack of response to conventional chemo-radiation. In the future, genetically-tailored therapies might improve the prognosis.

Abstract The Sars-CoV-2 pandemic catalysed integration of telemedicine worldwide. This systematic review assesses it’s accuracy for diagnosis of Surgical Site Infection (SSI). Databases were searched for telemedicine and wound infection studies. All types of studies were included, only paired designs were taken to meta-analysis. QUADAS-2 assessed methodological quality. 1400 titles and abstracts were screened, 61 full text reports were assessed for eligibility and 17 studies were included in meta-analysis, mean age was 47.1 ± 13.3 years. Summary sensitivity and specificity was 87.8% (95% CI, 68.4–96.1) and 96.8% (95% CI 93.5–98.4) respectively. The overall SSI rate was 5.6%. Photograph methods had lower sensitivity and specificity at 63.9% (95% CI 30.4–87.8) and 92.6% (95% CI, 89.9–94.5). Telemedicine is highly specific for SSI diagnosis is highly specific, giving rise to great potential for utilisation excluding SSI. Further work is needed to investigate feasibility telemedicine in the elderly population group.

PURPOSEThe co-occurrence of diabetes and cancer is becoming increasingly common, and this is likely to compound existing inequities in outcomes from both conditions within populations.METHODSIn this study, we investigate the co-occurrence of cancer and diabetes by ethnic groups in New Zealand. National-level diabetes and cancer data on nearly five million individuals over 44 million person-years were used to describe the rate of cancer in a national prevalent cohort of peoples with diabetes versus those without diabetes, by ethnic group (Māori, Pacific, South Asian, Other Asian, and European peoples).RESULTSThe rate of cancer was greater for those with diabetes regardless of ethnic group (age-adjusted rate ratios, Māori, 1.37; 95% CI, 1.33 to 1.42; Pacific, 1.35; 95% CI, 1.28 to 1.43; South Asian, 1.23; 95% CI, 1.12 to 1.36; Other Asian, 1.31; 95% CI, 1.21 to 1.43; European, 1.29; 95% CI, 1.27 to 1.31). Māori had the highest rate of diabetes and cancer co-occurrence. Rates of GI, endocrine, and obesity-related cancers comprised a bulk of the excess cancers occurring among Māori and Pacific peoples with diabetes.CONCLUSIONOur observations reinforce the need for the primordial prevention of risk factors that are shared between diabetes and cancer. Also, the commonality of diabetes and cancer co-occurrence, particularly for Māori, reinforces the need for a multidisciplinary, joined-up approach to the detection and care of both conditions. Given the disproportionate burden of diabetes and those cancers that share risk factors with diabetes, action in these areas is likely to reduce ethnic inequities in outcomes from both conditions.

Objectives Examine the impact of two generic—urban–rural experimental profile (UREP) and urban accessibility (UA)—and one purposely built—geographic classification for health (GCH)—rurality classification systems on the identification of rural–urban health disparities in Aotearoa New Zealand (NZ).Design A comparative observational study.Setting NZ; the most recent 5 years of available data on mortality events (2013–2017), hospitalisations and non-admitted hospital patient events (both 2015–2019).Participants Numerator data included deaths (n=156 521), hospitalisations (n=13 020 042) and selected non-admitted patient events (n=44 596 471) for the total NZ population during the study period. Annual denominators, by 5-year age group, sex, ethnicity (Māori, non-Māori) and rurality, were estimated from Census 2013 and Census 2018.Primary and secondary outcome measures Primary measures were the unadjusted rural incidence rates for 17 health outcome and service utilisation indicators, using each rurality classification. Secondary measures were the age-sex-adjusted rural and urban incidence rate ratios (IRRs) for the same indicators and rurality classifications.Results Total population rural rates of all indicators examined were substantially higher using the GCH compared with the UREP, and for all except paediatric hospitalisations when the UA was applied. All-cause rural mortality rates using the GCH, UA and UREP were 82, 67 and 50 per 10 000 person-years, respectively. Rural–urban all-cause mortality IRRs were higher using the GCH (1.21, 95% CI 1.19 to 1.22), compared with the UA (0.92, 95% CI 0.91 to 0.94) and UREP (0.67, 95% CI 0.66 to 0.68). Age-sex-adjusted rural and urban IRRs were also higher using the GCH than the UREP for all outcomes, and higher than the UA for 13 of the 17 outcomes. A similar pattern was observed for Māori with higher rural rates for all outcomes using the GCH compared with the UREP, and 11 of the 17 outcomes using the UA. For Māori, rural–urban all-cause mortality IRRs for Māori were higher using the GCH (1.34, 95% CI 1.29 to 1.38), compared with the UA (1.23, 95% CI 1.19 to 1.27) and UREP (1.15, 95% CI 1.10 to 1.19).Conclusions Substantial variation in rural health outcome and service utilisation rates were identified with different classifications. Rural rates using the GCH are substantially higher than the UREP. Generic classifications substantially underestimated rural–urban mortality IRRs for the total and Māori populations.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is frequently associated with type 2 diabetes. However, there is no specific medical therapy to treat this condition. Angiotensin‐converting enzyme 2 (ACE2) of the protective renin angiotensin system generates the antifibrotic peptide angiotensin‐(1‐7) from profibrotic angiotensin II peptide. In this study, we investigated the therapeutic potential of ACE2 in diabetic NAFLD mice fed a high‐fat (20%), high‐cholesterol (2%) diet for 40 weeks. Mice were given a single intraperitoneal injection of ACE2 using an adeno‐associated viral vector at 30 weeks of high‐fat, high‐cholesterol diet (15 weeks after induction of diabetes) and sacrificed 10 weeks later. ACE2 significantly reduced liver injury and fibrosis in diabetic NAFLD mice compared with the control vector injected mice. This was accompanied by reductions in proinflammatory cytokine expressions, hepatic stellate cell activation, and collagen 1 expression. Moreover, ACE2 therapy significantly increased islet numbers, leading to an increased insulin protein content in β‐cells and plasma insulin levels with subsequent reduction in plasma glucose levels compared with controls. Conclusion: We conclude that ACE2 gene therapy reduces liver fibrosis and hyperglycemia in diabetic NAFLD mice and has potential as a therapy for patients with NAFLD with diabetes.

Abstract Background Childhood asthma is an important unmet need. To date, patient-reported outcome measures (PROMs) for children with asthma have used a combination of caregiver or proxy-reported and self-reported measures. No comprehensive measure is available to assess the severity and impact of daytime and nighttime asthma symptoms and rescue medication use for self-completion by children aged 6–11 years. This study aimed to develop a novel, interactive, electronic Pediatric Asthma Symptom Diary (ePASD) measuring self-reported key symptom severity and proximal impacts of asthma in young children with varying reading ability and disease severity, consistent with US Food and Drug Administration (FDA) PRO guidance and the International Society for Health Economics and Outcomes Research (ISPOR) good research practices. Methods A targeted literature review and clinician interviews were undertaken to characterize symptoms and impacts experienced by children with mild-to-severe asthma. Concept elicitation interviews (CEIs) were conducted with 44 children and their caregivers (30 US; 14 UK). Following item and digital application development, the ePASD was assessed for relevance, understanding, and interpretability through cognitive debriefing interviews (CDIs) with 21 US children. Face validity/translatability assessments were also performed. Results Key measurement concepts included cough, wheeze, difficulty breathing, chest tightness/discomfort, nighttime awakening, and daytime activity limitations. Concept saturation was reached during CEIs for primary asthma-related daytime and nighttime symptoms and core impacts. Most CDI participants found the ePASD items clear, understandable, and comprehensive. Standardized training is anticipated to facilitate reliable child self-report. Conclusion The ePASD, a novel PROM for children aged 6–11 years with asthma, uses an innovative multimedia approach and has been developed in accordance with FDA PRO guidance and ISPOR good research practices, directly capturing the child’s self-reported asthma symptoms, impacts on daily activities and nighttime awakening, and rescue medication use.

Data-limited fisheries benefit from using life-history traits as biological indicators of targeted stocks. We used histology-based reproductive analyses to estimate size at maturity, per capita egg production, and the number and biomass of immature individuals in the catch for three common coral reef fishes in Fiji market surveys during 2010–2019. We studied Lutjanus gibbus (Forsskål, 1775), Parupeneus indicus (Shaw, 1803), and Chlorurus microrhinos (Bleeker, 1854), which represent three families: Lutjanidae, Mullidae, and Scaridae, respectively. Fork length comprising 50% mature individuals for females of L. gibbus was 22.7 cm, that of P. indicus was 25.9 cm, attaining 38.0 cm for C. microrhinos. Females were rare or absent in the largest size classes of all three species. Immature fish represented up to 50% by number and 41% by biomass of the catch in market surveys, with P. indicus having the greatest immature number (8%‒50%) and biomass (6%‒41%), followed by C. microrhinos (20%‒30% by count, 11%‒18% by biomass) and L. gibbus (9%‒28% by count, 5%‒14% by biomass). Individuals ≤ 30 cm for L. gibbus and P. indicus and ≤ 45 cm for C. microrhinos were responsible for ≥ 90% of egg production per spawning. Skewed size-specific sex ratios suggested that exploitation of the largest size classes had minimal effect on overall egg production. Decreased catches of immature fishes would increase the reproductive population sizes for these species.

Introduction Obesity is a multifaceted clinical and public health issue affecting over 34% of New Zealand adults. The Ministry of Health has positioned general practice as the best-suited location for addressing the health effects of obesity. Previous literature has identified barriers to the delivery of effective obesity management in general practice. Aim To explore Waikato GP perspectives to determine areas for improving the care of adults with weight problems. Methods A short exploratory questionnaire was used to collect data from 29 GPs across the Waikato region. Descriptive statistics and content analysis were used. Results The majority of GPs reported: they would wait for their patient to raise the issue of their weight; would offer weight advice themselves as a first option before considering referral; did not view general practice as best suited in tackling the obesity epidemic; and utilised bariatric surgery as a referral option while noting the inequities in access. Discussion The survey identified barriers to discussing weight with patients and in finding effective treatment options. Psychosocial and sociocultural aspects were recognised as contributing factors to obesity, but not highlighted as available treatment options. Bariatric surgery was reported as a viable option for treatment, but with barriers to access in the public system. This study found strong trends and themes, which identify an urgent need for further exploration into weight management pathways in New Zealand.

This study explores the experiences of refugee Muslim women as they accessed and navigated the healthcare system in Aotearoa New Zealand (NZ). A case-oriented approach was used, where semi-structured interviews were carried out with nine Muslim women who arrived in NZ as refugees. Interviews were carried out in 2020, in Hamilton, NZ. Analysis involved a ‘text in context’ approach which employed an iterative and interpretive process, by engaging with participant accounts and field notes to unpack the various meanings behind the experiences of the participants in relation to the literature as well as the broader socio-cultural contexts in which these experiences occurred. The findings of this research identified various structural barriers to accessing healthcare such as cost and issues with interpreters, as well as instances of othering in the healthcare settings experienced by refugee Muslim women. In order to tackle inequity in the health system, structural and institutional barriers need to be addressed first, to prompt other levels of othering and discrimination to reduce over time.

Abstract Background New Zealand has high rates of colorectal cancer (CRC) but poor outcomes. Most patients with CRC are diagnosed following referral from general practice, where a general practitioner (GP) assesses symptoms according to national guidelines. All referred patients are then re-prioritised by the hospital system. The first objective of this study was to identify what proportion of patients referred by general practice to surgical/gastroenterology at Waikato District Health Board (DHB) had a colonoscopy. The second objective was to determine what proportion of these referrals have an underlying CRC and the factors associated with the likelihood of this diagnosis. Methods This study is a retrospective analysis of e-referral data for patients aged 30–70+ who were referred from 75 general practices to general surgery, gastroenterology or direct to colonoscopy at Waikato DHB, 01 January 2015–31 December 2017. Primary and secondary outcome measures included the proportion and characteristics of patients who were having colonoscopy, and of those, who were diagnosed with CRC. Data were analysed using chi square and logistic regression. Results 6718/20648 (32.5%) patients had a colonoscopy and 372 (5.5%) of these were diagnosed with CRC. The probability of having CRC following a colonoscopy increased with age (p value

Summary: Background: Previous research identified inequities in all-cause mortality between Māori and non-Māori populations. Unlike comparable jurisdictions, mortality rates in rural areas have not been shown to be higher than those in urban areas for either population. This paper uses contemporary mortality data to examine Māori and non-Māori mortality rates in rural and urban areas. Methods: A population-level observational study using deidentified routinely collected all-cause mortality, amenable mortality and census data. For each level of the Geographic Classification for Health (GCH), Māori and non-Māori age-sex standardised all-cause mortality and amenable mortality incident rates, Māori:Non-Māori standardised incident rate ratios and Māori rural:urban standardised incident rate ratios were calculated. Age and deprivation stratified rates and rate ratios were also calculated. Findings: Compared to non-Māori, Māori experience excess all-cause (SIRR 1.87 urban; 1.95 rural) and amenable mortality (SIRR 2.45 urban; 2.34 rural) and in all five levels of the GCH. Rural Māori experience greater all-cause (SIRR 1.07) and amenable (SIRR 1.13) mortality than their urban peers. Māori and non-Māori all-cause and amenable mortality rates increased as rurality increased. Interpretation: The excess Māori all-cause mortality across the rural: urban spectrum is consistent with existing literature documenting other Māori health inequities. A similar but more pronounced pattern of inequities is observed for amenable mortality that reflects ethnic differences in access to, and quality of, health care. The excess all-cause and amenable mortality experienced by rural Māori, compared to their urban counterparts, suggests that there are additional challenges associated with living rurally. Funding: This work was funded by the Health Research Council of New Zealand (HRC19/488).

Abstract Androgen deprivation therapy (ADT) for men with prostate cancer (PCa) results in accelerated bone loss and increased risk of bone fracture. The aim of the present study was to evaluate serum bone markers—sclerostin, Dickkopf-1 (DKK-1) and osteoprotegerin (OPG), in a cohort of 88 PCa patients without known bone metastases, managed with and without ADT, and to analyse their relationship with bone mineral density (BMD) and sex steroids. The cross-sectional analysis between acute-, chronic- and former-ADT groups and PCa controls showed that sclerostin and OPG levels significantly differed between them (p = 0.029 and p = 0.032). Groups contributing to these significant changes were recorded. There were no significant differences in serum DKK-1 levels across the four groups (p = 0.683). In the longitudinal analysis, significant % decreases within groups were seen for DKK-1 [chronic-ADT (− 10.06%, p = 0.0057), former-ADT (− 12.77%, p = 0.0239), and in PCa controls group (− 16.73, p = 0.0022); and OPG levels in chronic ADT (− 8.28%, p = 0.003) and PCa controls group (− 12.82%, p = 0.017)]. However, % changes in sclerostin, DKK-1, and OPG did not differ significantly over 6-months across the evaluated groups. Sclerostin levels showed significant positive correlations with BMD at baseline in the ADT group, while in PCa controls this correlation existed at both baseline and 6-month time points. Sclerostin correlated negatively with testosterone in former ADT users and in PCa controls. Possible prognostic features denoted by parallel increases in sclerostin and BMD are discussed.

Introduction Lung cancer is the leading cause of cancer mortality, comprising the largest national cancer disease burden in Australia and New Zealand. Regional reports identify substantial evidence-practice gaps, unwarranted variation from best practice, and variation in processes and outcomes of care between treating centres. The Australia and New Zealand Lung Cancer Registry (ANZLCR) will be developed as a Clinical Quality Registry to monitor the safety, quality and effectiveness of lung cancer care in Australia and New Zealand.Methods and analysis Patient participants will include all adults >18 years of age with a new diagnosis of non-small-cell lung cancer (NSCLC), SCLC, thymoma or mesothelioma. The ANZLCR will register confirmed diagnoses using opt-out consent. Data will address key patient, disease, management processes and outcomes reported as clinical quality indicators. Electronic data collection facilitated by local data collectors and local, state and federal data linkage will enhance completeness and accuracy. Data will be stored and maintained in a secure web-based data platform overseen by registry management. Central governance with binational representation from consumers, patients and carers, governance, administration, health department, health policy bodies, university research and healthcare workers will provide project oversight.Ethics and dissemination The ANZLCR has received national ethics approval under the National Mutual Acceptance scheme. Data will be routinely reported to participating sites describing performance against measures of agreed best practice and nationally to stakeholders including federal, state and territory departments of health. Local, regional and (bi)national benchmarks, augmented with online dashboard indicator reporting will enable local targeting of quality improvement efforts.

Purpose Checkpoint therapy is now the cornerstone of treatment for patients with renal cell carcinoma (RCC) with advanced disease, but biomarkers are lacking to predict which patients will benefit. This study proposes potential immunological biomarkers that could developed for predicting therapeutic response in patients with RCC.Methods Using flow cytometry, RNA sequencing, and T-cell receptor (TCR) sequencing, we investigated changes in T cells in the peripheral blood of patients with advanced RCC after receiving immunotherapy. We used immunofluorescence (IF) imaging and flow cytometry to investigate how intratumoral T cells in patients’ tumors (resected months/years prior to receiving checkpoint therapy) predicted patient outcomes after immunotherapy.Results We found that a small proportion of CD4 and CD8 T cells in the blood activate following checkpoint therapy, expressing the proliferation marker Ki67 and activation markers HLA-DR and CD38. Patients who had the highest increase in these HLA-DR +CD38+CD8 T cells after treatment had the best antitumor immune response and experienced clinical benefit. Using RNA sequencing, we found that while these cells expanded in most patients, their phenotype did not drastically change during treatment. However, when we analyzed the TCR repertoire of these HLA-DR +CD38+CD8+T cells, we found that only patients who clinically benefitted had a burst of new clonotypes enter this pool of activated cells. Finally, we found that abundant T cells in the untreated tumors predicted clinical benefit to checkpoint therapy on disease progression.Conclusions Together, these data suggest that having a strong pre-existing immune response and immediate peripheral T-cell activation after checkpoint therapy is a predictor of clinical benefit in patients with RCC.