Use of Novel National Data Sets to Monitor Chemotherapy Use and Outcomes: A Retrospective Cohort Study of Non-Small-Cell Lung Cancer in Aotearoa New Zealand.

PURPOSE: Te Aho o Te Kahu, the New Zealand Cancer Control Agency, is establishing a systemic anticancer therapy (SACT) database (Anti-Cancer Therapy-Nationally Organized Workstream [ACT-NOW]) which can be linked to other national health data collections. In this article, we explore the application of ACT-NOW data in the monitoring of uptake and outcomes after the public funding of pemetrexed in Aotearoa New Zealand. METHODS: We used the ACT-NOW collection to identify patients with advanced nonsquamous non-small-cell lung cancer, who were treated with first-line platinum-based doublet chemotherapy over an 8-year period. Data were extracted for a period of 4 years before and 4 years after the national funding of pemetrexed (November 1, 2017). Treatments were classified as historical platinum doublet (cisplatin or carboplatin with gemcitabine, vinorelbine, paclitaxel, or docetaxel) or platinum pemetrexed doublet (cisplatin or carboplatin with pemetrexed). The primary outcome was the proportion of patients receiving each treatment type, before and after November 1, 2017. To prototype linkage to outcomes data, we evaluated hospitalization and 1-year overall survival (OS) rates by treatment. RESULTS: A total of 331 patients were included from four cancer centers. All patients (116 of 116) who were treated with first-line platinum-based doublet chemotherapy between November 2013 and November 2017 received historical platinum doublet chemotherapy. After the introduction of pemetrexed, between November 2017 and November 2021, 94% (203 of 215) were treated with platinum pemetrexed doublet chemotherapy and 6% (12 of 215) with historical platinum doublet chemotherapy. Linkage to outcomes data for 1-year OS, hospitalization rates, and lengths of stay outcome data were achievable. CONCLUSION: The ACT-NOW data set has the potential to facilitate evaluation of the impact of national-level SACT funding decisions on prescribing practice and specific patient outcomes. Our results support the use of these data to inform resource planning and quality improvement.

The past, present and future of liver cancer control for Maori.

Liver cancer is among the most commonly diagnosed and least-survivable cancers in New Zealand. There are stark disparities between the Indigenous Maori population in incidence of and mortality from liver cancer relative to non-Maori. In this review, we have summarised the key risk factors for liver cancer, and the key activities undertaken in New Zealand, over time, to control this disease, with a focus on how risk factors and interventions aimed at reducing them differentially impact Maori. We have conducted a narrative literature review. The disproportionate burden of liver cancer experienced by Maori is primarily driven by disparities in viral exposure to hepatitis B and C between ethnic groups. Efforts to control hepatitis-associated liver cancer in New Zealand have lacked national coordination, further driving disparities in liver cancer survival between Maori and NZ Europeans. A national primary care-based programme to detect and treat hepatitis B and C and to screen for liver cancer among high-risk patients, along with renewed effort to maximise hepatitis B vaccination rates, has the potential to substantially reduce the burden of hepatitis-associated liver cancer and address a significant health disparity between Maori and non-Maori.

The long road to good care.

Nil.

Understanding disparities in post-operative mortality for Indigenous patients.

There is an urgent need for high-quality evidence regarding post-operative mortality among Indigenous peoples. Our group recently published a national audit of 4,000,000 procedures conducted between 2005-2017, which identified considerable disparities in post-operative mortality between Indigenous Maori and non-Indigenous New Zealanders. Understanding the primary drivers of these disparities-for Maori, but likely also other Indigenous populations worldwide-requires us to consider the multiple levels at which these drivers might arise. To that end, in this paper we breakdown these drivers in detail, conceptualising these drivers as operating in layers with each factor leading to the next. These layers include structural factors, care system factors, care process factors, care team factors and patient factors. Each of these factors are presented within a framework that can be used to begin to understand them - with a view to rousing action and inspiring intervention to address inequities in post-operative outcomes experienced by Indigenous peoples.

The impact of COVID-19 on lung cancer detection, diagnosis and treatment for Maori in Aotearoa New Zealand.

AIM: The purpose of this article is to examine disparities in the impact of the COVID-19 pandemic on access to lung cancer diagnosis and access to clinical services between Maori and non-Maori. METHODS: Using national-level data, we examined age-standardised lung cancer registrations, diagnostic procedures (bronchoscopy) and lung surgeries separately by ethnic group for the years 2018-2020, as well as patterns of stage of diagnosis. RESULTS: We found a trend toward a reduction in rates of lung cancer registration in Maori (but not non-Maori/non-Pacific) New Zealanders in 2020 compared to 2018 and 2019, but no apparent shift in the distribution of stage at diagnosis. We found a trend toward a reduction in rates of bronchoscopy for both Maori and non-Maori/non-Pacific patients, with the largest reduction observed for Maori. Rates of lung cancer surgery appeared to have reduced for Maori patients, although this was based on a small number of procedures. CONCLUSIONS: We observed disparities between Maori and non-Maori/non-Pacific patients in lung cancer registration and bronchoscopy as a result of the COVID-19 pandemic.

Regional variation in post-operative mortality in New Zealand.

BACKGROUND: There is a growing body of evidence that access to best practice perioperative care varies within our population. In this study, we use national-level data to begin to address gaps in our understanding of regional variation in post-operative outcomes within New Zealand. METHODS: Using National Collections data, we examined all inpatient procedures in New Zealand public hospitals between 2005 and 2017 (859 171 acute, 2 276 986 elective/waiting list), and identified deaths within 30 days. We calculated crude and adjusted rates per 100 procedures for the 20 district health boards (DHBs), both for the total population and stratified by ethnicity (Maori/European). Odds ratios comparing the risk of post-operative mortality between Maori and European patients were calculated using crude and adjusted Poisson regression models. RESULTS: We observed regional variations in post-operative mortality outcomes. Maori, compared to European, patients experienced higher post-operative mortality rates in several DHBs, with a trend to higher mortality in almost all DHBs. Regional variation in patterns of age, procedure, deprivation and comorbidity (in particular) largely drives regional variation in post-operative mortality, although variation persists in some regions even after adjusting for these factors. Inequitable outcomes for Maori also persist in several regions despite adjustment for multiple factors, particularly in the elective setting. CONCLUSIONS: The persistence of variation and ethnic disparities in spite of adjustment for confounding and mediating factors suggests that multiple regions require additional resource and support to improve outcomes. Efforts to reduce variation and improve outcomes for patients will require both central planning and monitoring, as well as region-specific intervention.

Increased Breadth of Group A Streptococcus Antibody Responses in Children With Acute Rheumatic Fever Compared to Precursor Pharyngitis and Skin Infections.

BACKGROUND: Group A Streptococcus (GAS) causes superficial pharyngitis and skin infections as well as serious autoimmune sequelae such as acute rheumatic fever (ARF) and subsequent rheumatic heart disease. ARF pathogenesis remains poorly understood. Immune priming by repeated GAS infections is thought to trigger ARF, and there is growing evidence for the role of skin infections in this process. METHODS: We utilized our recently developed 8-plex immunoassay, comprising antigens used in clinical serology for diagnosis of ARF (SLO, DNase B, SpnA), and 5 conserved putative GAS vaccine antigens (Spy0843, SCPA, SpyCEP, SpyAD, Group A carbohydrate), to characterize antibody responses in sera from New Zealand children with a range of clinically diagnosed GAS disease: ARF (n = 79), GAS-positive pharyngitis (n = 94), GAS-positive skin infection (n = 51), and matched healthy controls (n = 90). RESULTS: The magnitude and breadth of antibodies in ARF was very high, giving rise to a distinct serological profile. An average of 6.5 antigen-specific reactivities per individual was observed in ARF, compared to 4.2 in skin infections and 3.3 in pharyngitis. CONCLUSIONS: ARF patients have a unique serological profile, which may be the result of repeated precursor pharyngitis and skin infections that progressively boost antibody breadth and magnitude.

Anaesthetic choice for hip or knee arthroplasty in New Zealand: Risk of postoperative death and variations in use.

Anaesthetic choice for large joint surgery can impact postoperative outcomes, including mortality. The extent to which the impact of anaesthetic choice on postoperative mortality varies within patient populations and the extent to which anaesthetic choice is changing over time remain under-explored both internationally and in the diverse New Zealand context. In a national study of 199,211 hip and knee replacement procedures conducted between 2005 and 2017, we compared postoperative mortality among those receiving general, regional or general plus regional anaesthesia. Focusing on unilateral (n=86,467) and partial (n=13,889) hip replacements, we assessed whether some groups within the population are more likely to receive general, regional or general plus regional anaesthesia than others, and whether mortality risk varies depending on anaesthetic choice. We also examined temporal changes in anaesthetic choice over time. Those receiving regional alone or general plus regional for unilateral hip replacement appeared at increased risk of 30-day mortality compared to general anaesthesia alone, even after adjusting for differences in terms of age, ethnicity, deprivation, rurality, comorbidity, American Society of Anesthesiologists physical status score and admission type (e.g. general plus regional: adjusted hazard ratio (adj. HR)=1.94, 95% confidence intervals (CI) 1.32 to 2.84). By contrast, we observed lower 30-day mortality among those receiving regional anaesthesia alone compared to general alone for partial hip replacement (adj. HR=0.86, 95% CI 0.75 to 0.97). The latter observation contrasts with declining temporal trends in the use of regional anaesthesia alone for partial hip replacement procedures. However, we recognise that postoperative mortality is one perioperative factor that drives anaesthetic choice.

National Study of Pain Medicine Access Among Maori and Non-Maori Patients With Lung Cancer in New Zealand.

PURPOSE: Pain is among the most common and consequential symptoms of cancer, particularly in the context of lung cancer. Maori have extremely high rates of lung cancer, and there is evidence that Maori patients with lung cancer are less likely to receive curative treatment and more likely to receive palliative treatment and to wait longer for their treatment than non-Maori New Zealanders. The extent to which Maori patients with lung cancer are also less likely to have access to pain medicines as part of their supportive care remains unclear. METHODS: Using national-level Cancer Registry and linked health records, we describe access to subsidized pain medicines among patients with lung cancer diagnosed over the decade spanning 2007-2016 and compare access between Maori and non-Maori patients. Descriptive and logistic regression methods were used to compare access between ethnic groups. RESULTS: We observed that the majority of patients with lung cancer are accessing some form of pain medicine and there do not appear to be strong differences between Maori and non-Maori in terms of overall access or the type of pain medicine dispensed. However, Maori patients appeared more likely than non-Maori to first access pain medicines within 2 weeks before their death and commensurately less likely to access them more than 24 weeks before death. CONCLUSION: Given the plausibility that there are differences in first access to pain medicines (particularly opioid medicines) among Maori approaching end of life, further investigation of the factors contributing to this disparity is required.

Patterns of age disparities in colon and lung cancer survival: a systematic narrative literature review.

OBJECTIVES: To identify patterns of age disparities in cancer survival, using colon and lung cancer as exemplars. DESIGN: Systematic review of the literature. DATA SOURCES: We searched Embase, MEDLINE, Scopus and Web of Science through 18 December 2020. ELIGIBILITY CRITERIA: We retained all original articles published in English including patients with colon or lung cancer. Eligible studies were required to be population-based, report survival across several age groups (of which at least one was over the age of 65) and at least one other characteristic (eg, sex, treatment). DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed the quality of included studies against selected evaluation domains from the QUIPS tool, and items concerning statistical reporting. We evaluated age disparities using the absolute difference in survival or mortality rates between the middle-aged group and the oldest age group, or by describing survival curves. RESULTS: Out of 3047 references, we retained 59 studies (20 for colon, 34 for lung and 5 for both sites). Regardless of the cancer site, the included studies were highly heterogeneous and often of poor quality. The magnitude of age disparities in survival varied greatly by sex, ethnicity, socioeconomic status, stage at diagnosis, cancer site, and morphology, the number of nodes examined and treatment strategy. Although results were inconsistent for most characteristics, we consistently observed greater age disparities for women with lung cancer compared with men. Also, age disparities increased with more advanced stages for colon cancer and decreased with more advanced stages for lung cancer. CONCLUSIONS: Although age is one of the most important prognostic factors in cancer survival, age disparities in colon and lung cancer survival have so far been understudied in population-based research. Further studies are needed to better understand age disparities in colon and lung cancer survival. PROSPERO REGISTRATION NUMBER: CRD42020151402.

The impact of the COVID-19 pandemic on cancer diagnosis and service access in New Zealand-a country pursuing COVID-19 elimination.

BACKGROUND: The COVID-19 pandemic has disrupted cancer services globally. New Zealand has pursued an elimination strategy to COVID-19, reducing (but not eliminating) this disruption. Early in the pandemic, our national Cancer Control Agency (Te Aho o Te Kahu) began monitoring and reporting on service access to inform national and regional decision-making. In this manuscript we use high-quality, national-level data to describe changes in cancer registrations, diagnosis and treatment over the course of New Zealand's response to COVID-19. METHODS: Data were sourced (2018-2020) from national collections, including cancer registrations, inpatient hospitalisations and outpatient events. Cancer registrations, diagnostic testing (gastrointestinal endoscopy), surgery (colorectal, lung and prostate surgeries), medical oncology access (first specialist appointments [FSAs] and intravenous chemotherapy attendances) and radiation oncology access (FSAs and megavoltage attendances) were extracted. Descriptive analyses of count data were performed, stratified by ethnicity (Indigenous Maori, Pacific Island, non-Maori/non-Pacific). FINDINGS: Compared to 2018-2019, there was a 40% decline in cancer registrations during New Zealand's national shutdown in March-April 2020, increasing back to pre-shutdown levels over subsequent months. While there was a sharp decline in endoscopies, pre-shutdown volumes were achieved again by August. The impact on cancer surgery and medical oncology has been minimal, but there has been an 8% year-to-date decrease in radiation therapy attendances. With the exception of lung cancer, there is no evidence that existing inequities in service access between ethnic groups have been exacerbated by COVID-19. INTERPRETATION: The impact of COVID-19 on cancer care in New Zealand has been largely mitigated. The New Zealand experience may provide other agencies or organisations with a sense of the impact of the COVID-19 pandemic on cancer services within a country that has actively pursued elimination of COVID-19. FUNDING: Data were provided by New Zealand's Ministry of Health, and analyses completed by Te Aho o Te Kahu staff.

Serological Profiling of Group A Streptococcus Infections in Acute Rheumatic Fever.

Rheumatic fever is a serious post-infectious sequela of group A Streptococcus (GAS). Prior GAS exposures were mapped in sera using a large panel of M-type specific peptides. Rheumatic fever patients had serological evidence of significantly more GAS exposures than matched controls suggesting immune priming by repeat infections contributes to pathogenesis.

The most commonly diagnosed and most common causes of cancer death for Maori New Zealanders.

Cancer is an important cause of morbidity and avoidable mortality for Maori-and substantial disparities exist in cancer incidence, mortality and survival for Maori compared to non-Maori New Zealanders. In this viewpoint, we draw together cancer incidence, mortality and survival data from the previous decade, in order to provide clarity regarding the most important causes of cancer burden for Maori. Covering the decade 2007-2016, our manuscript directly leads on from the landmark Unequal Impact II report (which covered 1996-2006), and provides the most up-to-date record of this burden as is currently possible. While focusing on the absolute burden of cancer for Maori, we also compare this burden to that experienced by non-Maori, and consider how this relative disparity may (or may not) have changed over time. Finally, we discuss how to reduce the occurrence and the overall cancer mortality burden for Maori, with a focus on those cancers that confer the greatest burden.

Postoperative mortality in New Zealand following general anaesthetic: demographic patterns and temporal trends.

OBJECTIVES: In this manuscript, we describe broad trends in postoperative mortality in New Zealand (a country with universal healthcare) for acute and elective/waiting list procedures conducted between 2005 and 2017. DESIGN, PARTICIPANTS AND SETTING: We use high-quality national-level hospitalisation data to compare the risk of postoperative mortality between demographic subgroups after adjusting for key patient-level confounders and mediators. We also present temporal trends and consider how rates in postoperative death following acute and elective/waiting list procedures have changed over this time period. RESULTS AND CONCLUSION: A total of 1 836 683 unique patients accounted for 3 117 374 admissions in which a procedure was performed under general anaesthetic over the study period. We observed an overall 30-day mortality rate of 0.5 per 100 procedures and a 90-day mortality rate of 0.9 per 100. For acute procedures, we observed a 30-day mortality rate of 1.6 per 100, compared with 0.2 per 100 for elective/waiting list procedures. In terms of procedure specialty, respiratory and cardiovascular procedures had the highest rate of 30-day mortality (age-standardised rate, acute procedures: 3-6 per 100; elective/waiting list: 0.7-1 per 100). As in other contexts, we observed that the likelihood of postoperative death was not proportionally distributed within our population: older patients, Maori patients, those living in areas with higher deprivation and those with comorbidity were at increased risk of postoperative death, even after adjusting for all available factors that might explain differences between these groups. Increasing procedure risk (measured using the Johns Hopkins Surgical Risk Classification System) was also associated with an increased risk of postoperative death. Encouragingly, it appears that risk of postoperative mortality has declined over the past decade, possibly reflecting improvements in perioperative quality of care; however, this decline did not occur equally across procedure specialties.

Systems immunology reveals a linked IgG3-C4 response in patients with acute rheumatic fever.

Acute rheumatic fever (ARF) and chronic rheumatic heart disease (RHD) are autoimmune sequelae of a Group A streptococcal infection with significant global mortality and poorly understood pathogenesis. Immunoglobulin and complement deposition were observed in ARF/RHD valve tissue over 50 years ago, yet contemporary investigations have been lacking. This study applied systems immunology to investigate the relationships between the complement system and immunoglobulin in ARF. Patients were stratified by C-reactive protein (CRP) concentration into high (≥10 µg mL-1 ) and low (<10 µg mL-1 ) groups to distinguish those with clinically significant inflammatory processes from those with abating inflammation. The circulating concentrations of 17 complement factors and six immunoglobulin isotypes and subclasses were measured in ARF patients and highly matched healthy controls using multiplex bead-based immunoassays. An integrative statistical approach combining feature selection and principal component analysis revealed a linked IgG3-C4 response in ARF patients with high CRP that was absent in controls. Strikingly, both IgG3 and C4 were elevated above clinical reference ranges, suggesting these features are a marker of ARF-associated inflammation. Humoral immunity in response to M protein, an antigen implicated in ARF pathogenesis, was completely polarized to IgG3 in the patient group. Furthermore, the anti-M-protein IgG3 response was correlated with circulating IgG3 concentration, highlighting a potential role for this potent immunoglobulin subclass in disease. In conclusion, a linked IgG3-C4 response appears important in the initial, inflammatory stage of ARF and may have immediate utility as a clinical biomarker given the lack of specific diagnostic tests currently available.

International Trends in the Incidence of Testicular Cancer: Lessons from 35 Years and 41 Countries.

BACKGROUND: Incidence rates of testicular cancer (TC) have been increasing in many countries since, at least, the mid-20th century without clear explanation. Examining the varying trends across countries and time provides clues to understanding the causes of TC. OBJECTIVE: We have presented incidence data from 41 countries and evaluated incidence trends for the 35-yr period from 1978 to 2012. DESIGN, SETTING, AND PARTICIPANTS: Cancer registry data from Cancer Incidence in Five Continents (CI5) volumes V-XI, CI5plus, and the NORDCAN database were analysed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Age-standardised rates of TC overall and by histological type were calculated. A joinpoint regression model of the natural log-transformed rates was used to calculate the average annual percent change (AAPC) in incidence. Age-period-cohort modelling was used to examine the effect of birth cohort on rates. RESULTS AND LIMITATIONS: While the highest incidence of TC remains in Northern Europe, the gap is closing between higher- and lower-incidence regions. Age-period-cohort modelling found flattening of risk among recent cohorts in Denmark and the UK, a steady increase in risk in the USA (particularly for seminomas), and an increase in risk among more recent cohorts in Costa Rica, Croatia, and Slovakia. CONCLUSIONS: The gap between low- and high-incidence countries is closing due to increases in the former and stabilisation in the latter. Understanding the causes of these and other differences in incidence rates between, and within, countries may help further our understanding of the aetiology of this cancer. PATIENT SUMMARY: We examined the rates of testicular cancer in different countries over time. These rates have been increasing, although the rates in high-incidence countries seem to be slowing down, while rates in low-incidence countries are catching up. These trends might help us understand what is causing testicular cancer in general.

Regional variation in the risk of lower-limb amputation among patients with diabetes in New Zealand.

BACKGROUND: Lower-limb amputation is one of the most substantial and debilitating consequences of diabetes mellitus; however, the risk of lower-limb amputation is not equally shared across the diabetic population. The aims of this study were to (i) describe regional variation in the rate of lower-limb amputation in New Zealand among a national prevalent cohort of patients with diabetes; and (ii) explore the plausible factors that could be contributing to this variation. METHODS: Our cohort were the national prevalent cohort of individuals with diabetes in New Zealand in 2011, according to the Virtual Diabetes Register (n = 215 676). Using descriptive analysis and Poisson regression, we compared the rate of lower-limb amputation within each of New Zealand's 20 District Health Boards with the national rate of amputation, adjusting for demographic, health care access and patient-level factors. RESULTS: We observed nearly four-fold variation in the rate of major lower-limb amputation between regions in New Zealand, as well as nearly two-fold variation in the rate of minor lower-limb amputation. Adjustment for differences between regions in terms of ethnicity reduced this variation substantially for many District Health Boards. Despite adjustment for sex, age, ethnicity, deprivation, rurality, comorbidity and prior amputation, the rate of lower-limb amputation in a number of District Health Boards remained substantially higher than the national rate. CONCLUSIONS: These observations could help to inform the funding and provision of diabetic foot care services across New Zealand; however, more work is required to further untangle the drivers of national variation in rates of lower-limb amputation.

Testicular Cancer in New Zealand (TCNZ) study: protocol for a national case-control study.

Testicular cancer (TC) is by far the most common cancer to affect young men; however, the exposures that cause this disease are still poorly understood. Our own research has shown that Maori men have the highest rates of this disease in New Zealand-a puzzling observation, since internationally TC is most commonly a disease of men of European ancestry. These trends provide us with a unique opportunity: to learn more about the currently unknown exposures that cause TC, and to explain why Maori have the highest rates of this disease in New Zealand. Using epidemiology and genetics, our experienced research team will conduct a nationwide study which aims to answer these internationally important questions. AIM OF STUDY: The overall aim of the current national case-control study is to identify the key exposures in the development of TC in New Zealand, and explore which factors might explain the difference in the incidence of TC between Maori and non-Maori. METHODS AND ANALYSIS: Outside of our own investigations into cryptorchidism, we still do not know which exposures are driving the significant incidence disparity between ethnic groups in NZ. The aim of the proposed research is to use a population-based case-control study to identify the key exposures in the development of TC in New Zealand. We will recruit 410 TC cases and 410 controls, and collect (1) environmental exposure data, via interview and (2) genetic information, via genome-wide genotyping. ETHICS AND DISSEMINATION: Ethical approval for this study was sought and received from the New Zealand Ministry of Health's Health and Disability Ethics Committee (reference # 17/NTA/248). Following a careful data interpretation process, we will disseminate the findings of this study to a wide and varied audience ranging from general academia, community groups and clinical settings, as well as to the participants themselves.

Dairy Consumption and Risk of Testicular Cancer: A Systematic Review.

Dairy consumption has been studied extensively in terms of its relationship with testicular cancer (TC), yet this relationship remains unclear. In this systematic review, we aimed to answer whether TC development is associated with (a) high amounts of dairy product consumption, (b) the type of dairy product consumed, (c) increasing levels of dairy product consumption, and (d) dairy consumption during certain periods during the lifecourse. Following a systematic review of the literature, eight studies (all case-control studies) were included in our review. The included studies varied in terms of the dairy product(s) investigated (milk, cheese, cream, butter, and yoghurt) as well as the type of exposure to dairy consumption (e.g., high vs. low exposure, dose-response, and timing during lifecourse). We found that there was no strong evidence that high levels of dairy consumption are associated with risk of TC, conflicting evidence of a dose-response relationship, inconsistent evidence on whether certain types of dairy are more strongly associated with TC than others, and conflicting evidence that exposure during certain life-course periods affects TC risk more than other periods. There is no consistent evidence to support the premise that dairy product consumption is associated with the risk of TC development.