Does diabetes affect breast cancer survival?

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 Rehita Mate Utaetae-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.

Facilitators and barriers for implementation of health programmes with Maori communities.

BACKGROUND: Addressing health inequities that Maori (Indigenous peoples) communities face in New Zealand is a key aim of researchers and practitioners. However, there is limited understanding of the implementation processes and outcomes of health programmes for addressing these inequities. The aim of this study was twofold: (a) to identify correlates of implementation outcomes and (b) to identify facilitators and barriers to implementation effectiveness. METHODS: The study involved a concurrent mixed method approach. Through an online survey, 79 participants with experience in implementing a health programme with a Maori community identified outcomes and processes of the programme. Additionally, nine Maori community providers shared their perceptions and experience of facilitators and barriers to implementation effectiveness through an in-depth interview. The quantitative and qualitative findings were integrated to address the aims of the study. RESULTS: For the first aim, we identified two key outcomes: overall health impacts and sustainability. Three of the variables had significant and positive bivariate correlations with health impacts: cultural alignment, community engagement, and individual skills. The only significant correlate of sustainability was evidence-based. For the second aim, participants described four facilitators (leadership, whanaungatanga [relationships], sharing information, digestible information) and four barriers (system constraints, lack of funding, cultural constraints, lack of engagement) to effective implementation. CONCLUSION: Overall, leadership, aligning culture, and building on whanaungatanga, while getting financial resources and systems support, are the core elements to supporting implementation efforts in Maori communities.

The growing cancer burden: Age-period-cohort projections in Aotearoa New Zealand 2020-2044.

BACKGROUND: Cancer is a major cause of premature death and inequity, and global case numbers are rapidly expanding. This study projects future cancer numbers and incidence rates in Aotearoa New Zealand. METHODS: Age-period-cohort modelling was applied to 25-years of national data to project cancer cases and incidence trends from 2020 to 2044. Nationally mandated cancer registry data and official historical and projected population estimates were used, with sub-groups by age, sex, and ethnicity. RESULTS: Cancer diagnoses were projected to increase from 25,700 per year in 2015-2019 to 45,100 a year by 2040-44, a 76% increase (2.3% per annum). Across the same period, age-standardised cancer incidence increased by 9% (0.3% per annum) from 348 to 378 cancers per 100,000 person years, with greater increases for males (11%) than females (6%). Projected incidence trends varied substantially by cancer type, with several projected to change faster or in the opposite direction compared to projections from other countries. CONCLUSIONS: Increasing cancer numbers reinforces the critical need for both cancer prevention and treatment service planning activities. Investment in developing new ways of working and increasing the workforce are required for the health system to be able to afford and manage the future burden of cancer.

Diabetes Cam: An Objective Methodology to Study Diabetes Self-Management.

INTRODUCTION: The prevalence of Type 2 Diabetes Mellitus (T2DM) is rapidly increasing throughout the world. T2DM is primarily a self-managed disease yet clinical studies indicate that a large proportion of adults with T2DM struggle to self-manage their diabetes. This puts them at high risk of developing diabetes-related complications. This study presents Diabetes Cam, a new methodology to objectively study T2DM self-management and identify its barriers and facilitators. METHODS: Thirty adults with diabetes of i-taukei descent from the 4 medical divisions throughout Fiji wore a camera for 4 days that automatically recorded images every 7 seconds. They also participated in in-depth photo-elicitation interviews to explore their experiences and perceptions of T2DM self-management. Data was collected between October 2021 and May 2022, and the analysis was done in August 2023. RESULTS: Approximately 11,500 images per participant were generated providing rich data. The method is ethical, legal, and acceptable for adults with T2DM, their families, and the wider community. The images can be readily coded for food availability and consumption, physical activity, transportation, medication use, and foot care. Photo-elicitation enabled further information on what was occurring within the images and about participants' perspectives on diabetes self-management. CONCLUSIONS: The Diabetes Cam methodology enabled automated, objective observation of participants' T2DM self-management and their perspectives on self-management. It provides unique insights into diabetes self-management and ways to improve diabetes self-management. It provides valuable data to develop strategies to enhance diabetes self-management for people living with diabetes, their families, the wider community, health professionals, and policymakers.

Cancer incidence, mortality and survival for Pacific Peoples in Aotearoa New Zealand.

AIMS: Pacific Peoples comprise over 16 culturally diverse ethnic groups and experience a disproportionate burden of preventable cancers, attributable to infectious diseases and obesity. This study aims to provide updated evidence on cancer incidence, mortality and survival rates among Pacific Peoples in Aotearoa New Zealand. METHODS: The study extracted incident cases of cancer diagnosed between 2007-2019 from the New Zealand Cancer Registry (NZCR) and linked them to the national Mortality Collection to determine individuals who died of cancer over the study period. The study also compared cancer survival rates between Pacific and European peoples in Aotearoa New Zealand. The most commonly diagnosed cancers and the most common causes of cancer death among Pacific Peoples were identified, and key findings were summarised. The European population was utilised as the comparator group for the analyses. The study employed a total ethnicity approach, wherein anyone with a record of Pacific ethnicity was classified as Total Pacific, regardless of other ethnicities. The age- and sex-standardised incidence and mortality rates were calculated, and 1-, 3- and 5-year survival rates determined. We used Cox proportional-hazards models to compare survival outcomes between Pacific and European peoples. CONCLUSIONS: The study results revealed that Pacific Peoples in Aotearoa New Zealand experience higher cancer incidence and a lower survival rate for several cancers, including lung, liver and stomach cancers, when compared to the European population. This study underscores the need for intervention to reduce the burden of cancer among Pacific Peoples and improve cancer outcomes. This study's findings can inform planning and delivery of interventions to achieve equitable outcomes across the cancer continuum for Pacific Peoples in Aotearoa New Zealand.

Equity of Cancer and Diabetes Co-Occurrence: A National Study With 44 Million Person-Years of Follow-Up.

PURPOSE: The 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. METHODS: In 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 (Maori, Pacific, South Asian, Other Asian, and European peoples). RESULTS: The rate of cancer was greater for those with diabetes regardless of ethnic group (age-adjusted rate ratios, Maori, 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). Maori 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 Maori and Pacific peoples with diabetes. CONCLUSION: Our 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 Maori, 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.

Impact of diabetes on surgery and radiotherapy for breast cancer.

PURPOSES: This study aims to examine whether diabetes has an impact on the use of surgery and adjuvant radiotherapy in treating women with localised breast cancer. METHODS: Women diagnosed with stage I-III breast cancer between 2005 and 2020 were identified from Te Rehita Mate Utaetae-Breast Cancer Foundation New Zealand National Register, with diabetes status determined using New Zealand's Virtual Diabetes Register. The cancer treatments examined included breast conserving surgery (BCS), mastectomy, breast reconstruction after mastectomy, and adjuvant radiotherapy after BCS. Logistic regression modelling was used to estimate the adjusted odds ratio (OR) and 95% confidence interval (95% CI) of having cancer treatment and treatment delay (> 31 days) for patients with diabetes at the time of cancer diagnosis compared to patients without diabetes. RESULTS: We identified 25,557 women diagnosed with stage I-III breast cancer in 2005-2020, including 2906 (11.4%) with diabetes. After adjustment for other factors, there was no significant difference overall in risk of women with diabetes having no surgery (OR 1.12, 95% CI 0.94-1.33), although for patients with stage I disease not having surgery was more likely (OR 1.45, 95% CI 1.05-2.00) in the diabetes group. Patients with diabetes were more likely to have their surgery delayed (adjusted OR of 1.16, 95% CI 1.05-1.27) and less likely to have reconstruction after mastectomy compared to the non-diabetes group-adjusted OR 0.54 (95% CI 0.35-0.84) for stage I cancer, 0.50 (95% CI 0.34-0.75) for stage II and 0.48 (95% CI 0.24-1.00) for stage III cancer. CONCLUSIONS: Diabetes is associated with a lower likelihood of receiving surgery and a greater delay to surgery. Women with diabetes are also less likely to have breast reconstruction after mastectomy. These differences need to be taken in to account when considering factors that may impact on the outcomes of women with diabetes especially for Maori, Pacific and Asian women.

Association of diabetes and breast cancer characteristics at diagnosis.

PURPOSE: This study aims to examine the association of diabetes and breast cancer characteristics at diagnosis in Aotearoa/New Zealand. METHODS: Patients diagnosed with invasive breast cancer between 2005 and 2020 were identified from the National Breast Cancer Register. Logistic regression modeling was used to estimate the adjusted odds ratio (OR) of having stage III-IV cancer and the OR of having stage IV cancer for women with diabetes compared to those without diabetes. The adjusted OR of having screen-detected breast cancers for patients aged 45-69 years with diabetes compared to patients without diabetes was estimated. RESULTS: 26,968 women were diagnosed with breast cancer, with 3,137 (11.6%) patients having diabetes at the time of cancer diagnosis. The probability of co-occurrence of diabetes and breast cancer increased with time. Maori, Pacific and Asian women were more likely to have diabetes than European/Others. The probability of having diabetes also increased with age. For patients with diabetes, the probability of being diagnosed with stage III-IV cancer and stage IV cancer was higher than for patients without diabetes (OR 1.14, 95% CI 1.03-1.27; and 1.17, 95% CI 1.00-1.38). Women aged 45-69 years with diabetes were more likely to have screen-detected cancer than those without diabetes (OR 1.13, 95% CI 1.02-1.26). CONCLUSIONS: The co-occurrence of diabetes and breast cancer is becoming more common. Overall there is a small but significant adverse impact of having advanced disease for women with diabetes that is found at the time of breast cancer diagnosis, and this may contribute to other inequities that occur in the treatment pathway that may impact on patient outcomes.

Cancer and diabetes co-occurrence: A national study with 44 million person-years of follow-up.

The number of new cases of cancer is increasing each year, and rates of diabetes mellitus are also increasing dramatically over time. It is not an unusual occurrence for an individual to have both cancer and diabetes at the same time, given they are both individually common, and that one condition can increase the risk of the other. In this manuscript, we use national-level diabetes (Virtual Diabetes Register) and cancer (New Zealand Cancer Registry) data on nearly five million individuals over 44 million person-years of follow-up to examine the occurrence of cancer amongst a national prevalent cohort of patients with diabetes. We completed this analysis separately by cancer for the 24 most commonly diagnosed cancers in Aotearoa New Zealand, and then compared the occurrence of cancer among those with diabetes to those without diabetes. We found that the rate of cancer was highest amongst those with diabetes for 21 of the 24 most common cancers diagnosed over our study period, with excess risk among those with diabetes ranging between 11% (non-Hodgkin's lymphoma) and 236% (liver cancer). The cancers with the greatest difference in incidence between those with diabetes and those without diabetes tended to be within the endocrine or gastrointestinal system, and/or had a strong relationship with obesity. However, in an absolute sense, due to the volume of breast, colorectal and lung cancers, prevention of the more modest excess cancer risk among those with diabetes (16%, 22% and 48%, respectively) would lead to a substantial overall reduction in the total burden of cancer in the population. Our findings reinforce the fact that diabetes prevention activities are also cancer prevention activities, and must therefore be prioritised and resourced in tandem.

Healthier Lives Implementation Research Network for Maori and Pacific community health providers in Aotearoa New Zealand: a study protocol with an observational mixed methods design.

BACKGROUND: Despite incremental gains in the Aotearoa New Zealand health sector, Maori and Pacific peoples still experience poorer health outcomes than non-Maori and non-Pacific. Access to the latest research and innovation is critical to improving and addressing health outcomes and health inequities in particular. However, there are numerous challenges to translating research into practice including that there is currently no known a specific infrastructure in Aotearoa New Zealand to facilitate this process. The aim of the project is to develop a network of community providers, researchers and health systems representatives that can help facilitate the implementation of novel and innovative programmes and products that help to meet the health needs of Maori and Pacific communities. METHODS: This project has three stages, one of which has been completed. In Stage 1, we engaged with key leaders of organisations from various components in the health system through a co-design process to identify parameters and infrastructure of the network. In Stage 2, we propose to construct the network involving approximately 20-30 community providers (and other affiliated researchers and health system representatives) and refine its parameters through an additional co-design process. Additionally, we will use a mixed methods research design using survey and interviews to identify perceived implementation needs, facilitators and barriers to help inform the work in the third stage. In Stage 3, we will support the active implementation of evidence-based programmes with a smaller number of providers (approximately four to eight community providers depending on the complexity of the implementation). Mixed methods research will be conducted to understand facilitators and barriers to implementation processes and outcomes. DISCUSSION: The proposed network infrastructure is an equity-oriented strategy focused on building capacity through a strength-based approach that can help address inequities over time. Our "proof-of-concept" study will not be able to change inequities in that time period given its relatively small scale and time period, but it should set the foundation for continued equity-oriented work.

Risk factors for group A streptococcal pharyngitis and skin infections: A case control study.

Background: Group A streptococcal (GAS) infections can trigger an immune-mediated response resulting in acute rheumatic fever (ARF). The role of social and environmental risk factors for GAS pharyngitis and skin infections are not well understood. This study aimed to identify factors associated with GAS pharyngitis and skin infections, and to determine if these are the same as those for ARF. Methods: A case-control study, including 733 children aged 5-14 years, was undertaken between March 2018 and October 2019 in Auckland, New Zealand. Healthy controls (n = 190) and symptomatic cases including GAS pharyngitis (n = 210), GAS seronegative carriers (n = 182), and GAS skin infections (n = 151) were recruited. Trained interviewers administered a comprehensive, pre-tested, face-to-face questionnaire. Findings: Multivariable analysis identified strong associations between barriers to accessing primary healthcare and having GAS pharyngitis (adjusted OR 3·3; 95% CI 1·8-6·0), GAS carriage (aOR 2·9; 95% CI 1·5-6·0) or a GAS skin infection (aOR 3·5; 95% CI 1·6-7·6). Children who had GAS skin infections were more likely than all other groups to report living in a crowded home (aOR 1·9; 95% CI 1·0-3·4), have Maori or Pacific grandparents (aOR 3·0; 95% CI 1·2-7·6), a family history of ARF (aOR 2·2; 95% CI 1·1-4·3), or having a previous diagnosis of eczema (aOR 3·9; 95% CI 2·2-6·9). Interpretation: Reducing barriers to accessing primary healthcare (including financial restrictions, the inability to book an appointment, lack of transport, and lack of childcare for other children) to treat GAS pharyngitis and skin infections could potentially reduce these infections and lead to a reduction in their sequelae, including ARF. These strategies should be co-designed and culturally appropriate for the communities being served and carefully evaluated. Funding: This work was supported by the Health Research Council of New Zealand (HRC), award number 16/005.

Ethnically Disparate Disease Progression and Outcomes among Acute Rheumatic Fever Patients in New Zealand, 1989-2015.

We investigated outcomes for patients born after 1983 and hospitalized with initial acute rheumatic fever (ARF) in New Zealand during 1989-2012. We linked ARF progression outcome data (recurrent hospitalization for ARF, hospitalization for rheumatic heart disease [RHD], and death from circulatory causes) for 1989-2015. Retrospective analysis identified initial RHD patients <40 years of age who were hospitalized during 2010-2015 and previously hospitalized for ARF. Most (86.4%) of the 2,182 initial ARF patients did not experience disease progression by the end of 2015. Progression probability after 26.8 years of theoretical follow-up was 24.0%; probability of death, 1.0%. Progression was more rapid and ≈2 times more likely for indigenous Maori or Pacific Islander patients. Of 435 initial RHD patients, 82.2% had not been previously hospitalized for ARF. This young cohort demonstrated low mortality rates but considerable illness, especially among underserved populations. A national patient register could help monitor, prevent, and reduce ARF progression.

Rising Ethnic Inequalities in Acute Rheumatic Fever and Rheumatic Heart Disease, New Zealand, 2000-2018.

We describe trends in acute rheumatic fever (ARF), rheumatic heart disease (RHD), and RHD deaths among population groups in New Zealand. We analyzed initial primary ARF and RHD hospitalizations during 2000-2018 and RHD mortality rates during 2000-2016. We found elevated rates of initial ARF hospitalizations for persons of Maori (adjusted rate ratio [aRR] 11.8, 95% CI 10.0-14.0) and Pacific Islander (aRR 23.6, 95% CI 19.9-27.9) ethnicity compared with persons of European/other ethnicity. We also noted higher rates of initial RHD hospitalization for Maori (aRR 3.2, 95% CI 2.9-3.5) and Pacific Islander (aRR 4.6, 95% CI 4.2-5.1) groups and RHD deaths among these groups (Maori aRR 12.3, 95% CI 10.3-14.6, and Pacific Islanders aRR 11.2, 95% CI 9.1-13.8). Rates also were higher in socioeconomically disadvantaged neighborhoods. To curb high rates of ARF and RHD, New Zealand must address increasing social and ethnic inequalities.

Quality of benzathine penicillin G: A multinational cross-sectional study.

Benzathine penicillin G (BPG) is used as first-line treatment for most forms of syphilis and as secondary prophylaxis against rheumatic heart disease (RHD). Perceptions that poor quality of BPG is linked to reported adverse effects and therapeutic failure may impact syphilis and RHD control programs. Clinical networks and web-based advertising were used to obtain vials of BPG from a wide range of countries. The quality of BPG was assessed using a high performance liquid chromatography assay capable of detecting relevant impurities and degradation products. Tests for water content, presence of heavy metals and physical characteristics of BPG, including particle size analysis and optical microscopy, also were conducted. Thirty-five batches of BPG were sourced from 16 countries across 4 WHO regions. All batches passed the US Pharmacopeia requirements for BPG injection (content), with no evidence of breakdown products or other detected contaminants. Water content and heavy metal analysis (n = 11) indicated adherence to regulatory standards and Good Manufacturing Practice. Particle size analysis (n = 20) found two batches with aggregated particles (>400 µm) that were dispersed following sonication. Current batches of BPG were of satisfactory pharmaceutical quality but aggregated particles were found in a modest proportion of samples. Future studies should focus on the physical characteristics of BPG which may contribute to variations in plasma penicillin concentrations an observed needle blockages in clinical practice. Pharmacopeial monographs could be revised to include standards on particle size and crystal morphology of BPG.

Uncovering social structures and informational prejudices to reduce inequity in delivery and uptake of new molecular technologies.

Advances in molecular technologies have the potential to help remedy health inequities through earlier detection and prevention; if, however, their delivery and uptake (and therefore any benefits associated with such testing) are not more carefully considered, there is a very real risk that existing inequities in access and use will be further exacerbated. We argue this risk relates to the way that information and knowledge about the technology is both acquired and shared, or not, between health practitioners and their patients.A healthcare system can be viewed as a complex social network comprising individuals with different worldviews, hierarchies, professional cultures and subcultures and personal beliefs, both for those giving and receiving care. When healthcare practitioners are not perceived as knowledge equals, they would experience informational prejudices, and the result is that knowledge dissemination across and between them would be impeded. The uptake and delivery of a new technology may be inequitable as a result. Patients would also experience informational prejudice when they are viewed as not being able to understand the information that is presented to them, and information may be withheld.Informational prejudices driven by social relations and structures have thus far been underexplored in considering (in)equitable implementation and uptake of new molecular technologies. Every healthcare interaction represents an opportunity for experiencing informational prejudice, and with it the risk of being inappropriately informed for undertaking (or offering) such screening or testing. Making knowledge acquisition and information dissemination, and experiences of informational prejudice, explicit through sociologically framed investigations would extend our understandings of (in)equity, and offer ways to affect network relationships and structures that support equity in delivery and uptake.

Understanding group A streptococcal pharyngitis and skin infections as causes of rheumatic fever: protocol for a prospective disease incidence study.

BACKGROUND: Group A Streptococcal (GAS) infections cause the autoimmune disease acute rheumatic fever (ARF), which can progress to chronic rheumatic heart disease (RHD). Treating pharyngitis caused by GAS with antibiotics is important in preventing ARF. However, it is difficult to distinguish these infections from GAS carriers. There is growing evidence for GAS skin infections as a cause of ARF. This study will identify the incidence of true GAS pharyngitis and serological responses to GAS skin infections. The effectiveness of antibiotics for these conditions will be explored, and modifiable risk factors. Serum antibody titres indicating the upper limits of normal (ULN for ASO/ADB antibodies) will be established alongside carriage rates in asymptomatic children. METHODS: This is a prospective disease incidence study, with an associated case-control study. The study population includes 1000 children (5-14 years) from Auckland, New Zealand, 800 of whom have visited their healthcare professional, resulting in a throat or skin swab for GAS, and 200 who are asymptomatic. The conditions of interest are GAS throat swab positive pharyngitis (n = 200); GAS carriage (n = 200); GAS negative throat swab (n = 200); GAS skin infections (n = 200); and asymptomatic controls (n = 200). All participants, except asymptomatic controls, will have acute and convalescent serological testing for ASO/ADB titres (collected < 9 days, and 2-4 weeks following symptom onset, respectively), alongside viral PCR from throat swabs. Asymptomatic controls will have ASO/ADB titres measured in one blood specimen and a throat swab for microbial culture. Caregivers of children will be interviewed using a questionnaire and any GAS isolates identified will be emm typed. The persistence of GAS antibodies will also be investigated. DISCUSSION: Findings from this study will fill critical gaps in scientific knowledge to better understand the pathophysiology of ARF, improve clinical management of GAS infections, and design more effective ARF prevention programmes. In particular it will measure the incidence of true, serologically confirmed GAS pharyngitis; assess the immune response to GAS skin infections and its role as a cause of ARF; examine the effectiveness of oral antibiotics for treating GAS pharyngitis and carriage; and identify whether risk factors for GAS infections might provide intervention points for reducing ARF.

A population pharmacokinetic study of benzathine benzylpenicillin G administration in children and adolescents with rheumatic heart disease: new insights for improved secondary prophylaxis strategies.

BACKGROUND: Benzathine benzylpenicillin G (BPG) is recommended as secondary prophylaxis to prevent recurrence of acute rheumatic fever and subsequent rheumatic heart disease (RHD). Following intramuscular injection, BPG is hydrolysed to benzylpenicillin. Little is known of the pharmacokinetics of benzylpenicillin following BPG in populations at risk of RHD. METHODS: We conducted a longitudinal pharmacokinetic study of children and adolescents receiving secondary prophylaxis throughout six monthly cycles of BPG. Dried blood spot samples were assayed with LC-MS/MS. Benzylpenicillin concentrations were analysed using non-linear mixed-effects modelling with subsequent simulations based on published BMI-for-age and weight-for-age data. RESULTS: Eighteen participants contributed 256 concentrations for analysis. None had benzylpenicillin concentrations >0.02 mg/L for the full time between doses. The median duration above this target was 9.8 days for those with a lower BMI (<25 kg/m2), who also had lower weights, and 0 days for those with a higher BMI (≥25 kg/m2). Although fat-free mass was a key determinant of benzylpenicillin exposure after a standard dose of BPG, having a higher BMI influenced absorption and almost doubled (increase of 86%) the observed t½. CONCLUSIONS: Few children and adolescents receiving BPG as secondary prophylaxis will achieve concentrations >0.02 mg/L for the majority of the time between injections. The discordance of this observation with reported efficacy of BPG to prevent rheumatic fever implies a major knowledge gap relating to pharmacokinetic/pharmacodynamic relationships between benzylpenicillin exposure and clinical outcomes.

Genomic medicine must reduce, not compound, health inequities: the case for hauora-enhancing genomic resources for New Zealand.

Precision medicine seeks to draw on data from both individuals and populations across disparate domains to influence and support diagnosis, management and prevention in healthcare at the level of the individual patient and their family/whanau. Central to this initiative is incorporating the effects of the inherent variation that lies within genomes and can influence health outcomes. Identifying and interpreting such variation requires an accurate, valid and representative dataset to firstly define what variants are present and then assess the potential relevance for the health of a person, their family/whanau and the wider community to which they belong. Globally the variation embedded within genomes differs enormously and has been shaped by the size, constitution, historical origins and evolutionary history of their source populations. Maori, and more broadly Pacific peoples, differ substantially in terms of genomic variation compared to the more closely studied European and Asian populations. In the absence of accurate genomic information from Maori and Pacific populations, the precise interpretation of genomic data and the success and benefits of genomic medicine will be disproportionately less for those Maori and Pacific peoples. In this viewpoint article we, as a group of healthcare professionals, researchers and scientists, present a case for assembling genomic resources that catalogue the characteristics of the genomes of New Zealanders, with an emphasis on peoples of Maori and Polynesian ancestry, as a healthcare imperative. In proposing the creation of these resources, we note that their governance and management must be led by iwi and Maori and Pacific representatives. Assembling a genomic resource must be informed by cultural concepts and values most especially understanding that, at a physical and spiritual level, whakapapa is embodied within the DNA of a person. Therefore DNA and genomic data that connects to whakapapa (genealogy) is considered a taonga (something precious and significant), and its storage, utilisation and interpretation is a culturally significant activity. Furthermore, such resources are not proposed to primarily enable comparisons between those with Maori and broader Pacific ancestries and other Aotearoa peoples but to place an understanding of the genetic contributors to their health outcomes in a valid context. Ongoing oversight and governance of such taonga by Maori and Pacific representatives will maximise hauora (health) while also minimising the risk of misuse of this information.