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Patient perspectives on the causes and prevention of rehospitalisation for exacerbations of chronic obstructive pulmonary disease: A qualitative study
Background: Chronic obstructive pulmonary disease (COPD) is the umbrella term for a group of lung diseases which are degenerative and marked by progressively worsening symptoms including: breathlessness; fatigue; acute exacerbation; multiple comorbidities; and eventually death.
Acute exacerbations of COPD (AECOPD) resulting in hospitalisation may be responsible for up to 25 percent of reductions in lung function. In New Zealand an estimated 23% of those discharged from hospital after an initial episode of AECOPD are readmitted within 30 days, a situation which is both costly and disadvantageous to the patient.
Objective: The aim of this study was to understand patients’ perspectives on the causes and prevention of re-hospitalisation for AECOPD.
Method: Data for this study was collected from a subgroup of participants who had been recruited as part of a feasibility study using randomised controlled trial methods to explore the effectiveness of a novel self-management intervention, called “Taking Charge of COPD”. All participants were initially recruited in hospital after an episode of severe AECOPD. The subgroup of participants in this qualitative study were interviewed 12 months later and ask about their views and experiences regarding what had helped or hindered them to stay well and out of hospital. Grounded theory was used to analyse results and construct concept. Data were also collected on disease specific health status (using the Chronic COPD Questionnaire), depression and anxiety (using the Hospital Depression and Anxiety Scale), and number of moderate episodes (requiring antibiotics or steroids) or severe episodes of AECOPD (requiring hospitalisation) during the prior 12 months.
Results: Twelve participants were interviewed (mean age 69.3 years (SD 13.6); range 29 – 84; 6 female, 2 Māori, 2 Pacific, 7 New Zealand European). These participants had experienced between 0 and 7 episodes of moderate AECOPD (average 1.8) and 0 to 3 episodes of severe AECOPD (average 0.7) in the 12 months since their original hospitalisation. Three main concepts were identified to describe the participants’ views on what helped or hinder them to stay well and out of hospital: 1) Being Proactive – which encompasses practical steps participants took to reduce AECOPD; 2) Being Positive – which describes the importance of a positive mindset; and 3) Taking Charge – the concept of believing in oneself. Impacting on each of these was the influence of significant others, particularly family and friends.
Conclusion: This research expands our understanding of how patients manage COPD and adds a patient’s perspective to the current knowledge on how to prevent AECOPD. Programmes which promote self-efficacy and positive mental health would be beneficial additions to AECOPD prevention, as could the inclusion of family or significant others in health planning/treatment plans.
The effects of catalytic innovation on the creation of social impact
Social innovation (SI) is increasingly being appraised to possess the potential to provide innovative interventions to confront complex and interdependent social problems in both developing and developed economies. SI has also been described as a complex phenomenon that combines two diverse concepts, i.e., social and innovation. Hence, several conceptualisations of SI have emerged in the literature, leading to ambiguity and lack of a robust strategy to create SI.
Drawing on entrepreneurial orientation, top management support, and stakeholder engagement literature strands, this study conceptualises and examines the antecedents and consequences of disruptive innovation for social change. Pragmatism as a research paradigm provides philosophical support for the integration of otherwise distinct research methods, i.e., qualitative and quantitative methods, allowing for grounded theory method and a multistage multiple regression to be combined within this study.
The study adopts a sequential mixed methods research (MMR) approach which includes, in the first phase, a grounded theory method to collect and analyse in-depth exploratory interview data from CEOs and top management executives of 20 social organisations in four countries, with the purpose of testing hypotheses between innovation management logics and creating social impact. In the second phase, the hypotheses are tested on a sample of 71 social organisations in 23 countries.
This study finds that entrepreneurial orientation, management support, and stakeholder engagement are antecedents of catalytic innovation. The results reveal that location of headquarters, type, and size of social organisations play a significant role in the creation of social innovation. The findings also show that for-profit social organisations have better economic performance, while not-for-profit social organisations have better social performance. Lastly, the results reveal that greater social performance may lead to greater social impact, while focus on economic performance may reduce the level of social impact achieved by these organisations. Additionally, the study reveals challenges and risks that social organisations face when creating social innovation, and proposes a framework that may help mitigate these risks and challenges.
The study offers a threefold contribution to social innovation literature, methodology, and implications for practitioners. The study advances the discourse of entrepreneurial orientation, top management support, and stakeholder engagement in the social innovation literature. The study also gives credence to claims justifying the applicability and compatibility of qualitative and quantitative methods within a study to provide robust and satisfactory answers to research questions. The results exemplify some of the advantages of MMR approach, that it is an appropriate research method in conceptualising antecedents of catalytic innovation. Lastly, the study provides recommendations to practitioners within the social organisation and social innovation space
Public Participation in Conservation: The Taranaki Mounga Project
This research is focused on critically reviewing and examining the nature of public participation in conservation through the lens of a landscape-scale conservation project; the Taranaki Mounga Project (TMP). TMP’s goal is to restore the ecological vitality and mauri (life essence) of Mount Taranaki and the surrounding environment. This research takes a qualitative approach to answer the main research question how does TMP employ public participation in conservation? through asking key informants from four different aspects of public participation in conservation (iwi representatives, TMP employees, local authority employees and volunteers) about their perspectives and impressions of how TMP uses public participation, and what makes public participation successful.
Key areas explored by this research are: how Māori are engaged in conservation by TMP, how legislation impacts public participation in conservation, how conservation projects can act be a platform for personal and community benefits, and how conservation projects can achieve engagement with the public.
This research also provides implications for current or future conservation projects to use public participation successfully within the context of conservation
The impact of thumb carpometacarpal osteoarthritis and the effectiveness of splinting
Background: Thumb carpometacarpal (CMC) osteoarthritis (OA) is a common, disabling condition, affecting substantial numbers of working and older-age people. It is the single commonest site affected by OA yet its unique characteristics, distinct from general hand OA, have received little individual attention – far less than hip and knee OA. In particular, little is known from patients’ perspectives about the impact of thumb CMC OA. Furthermore, international guidelines recommend splinting as a non-surgical, non- pharmacological treatment option for CMC OA; however, evidence supporting splinting in people with thumb CMC OA is sparse and inconsistent.
The aims of this research were to: 1) explore the impact of thumb CMC OA from the perspective of people living with the condition; 2) investigate the effectiveness of splinting interventions for thumb CMC OA.
Methods: Three main studies were conducted: 1) a pragmatic qualitative study exploring the impact of thumb CMC OA in 30 individual interviews of people with the condition; 2) a systematic review with meta-analyses of previous studies reporting on the effectiveness of splinting for thumb CMC OA; 3) a feasibility study for a future fully-powered randomised controlled trial (RCT) investigating the effectiveness of a soft splint intervention combined with standardised best practice usual care vs best practice usual care alone comparator intervention. Design of the feasibility study was based on the findings from the qualitative study and the systematic review.
Results: The qualitative study identified five main themes representing five inter-related levels of health impact: negative experience of symptoms, functional limitations, restricted social activities and roles, negative thoughts and feelings, and altered sense of self. Pain, including pain at night, was the major concern. CMC OA impact was influenced by: dominant hand involvement; cold climate; people’s financial, social, and societal support; and attitudes to the condition. Many areas of impact are unidentified and missing in currently recommended patient-reported outcomes. The study found a strong desire for access to high-quality information about self-management and effective non-surgical, non-pharmacological treatment options.
All evidence for splinting was of low quality. Splints cause a moderate-to-large reduction in pain (SMD -0.7 [95% CI -1.04, -0.35], < 0.0001) and small-to-moderate improvement in function (SMD -0.42 [-0.77, -0.08], p = 0.02) in the medium-term (3-12 months). No effect exists in the short-term. The review identified: variability in self-reported outcomes, case definitions, and rationale for splinting; low and variable splint dosage; lack of standardised usual care; unassessed QoL; and inappropriate study designs.
In the feasibility study, all primary outcomes surpassed the a priori thresholds for feasibility. Of thirty enrolled participants, 29 (97%) were retained at the 4-week and 6-month follow-ups. Interventions were acceptable and safe. Preliminary clinical findings suggested greater improvements in pain in the splint group vs comparator intervention in the short-term.
Conclusions: Thumb CMC OA has a profound impact on a person’s health and well-being. Splinting is an acceptable and promising intervention although good quality evidence to support its use is lacking. A full RCT of splinting in addition to standardised best practice usual care for thumb CMC OA pain is feasible but should be preceded by exploration of dose effect and optimisation of outcome measures
Demographic and reproductive variability within and among subpopulations of temperate reef fishes
Traditionally, fisheries management has assumed that all fish within a marine population contribute the same per unit biomass to population growth. However, it has become evident that older, larger individuals may contribute more to the reproductive output and success. Relatively small subpopulations may sustain a large population network, by contributing a reproductive surplus to the larval pool. For the sustainable management of marine fish populations, it is crucial to understand the reproductive contribution of populations and individual fish within populations, how populations are structured and connected, and how populations interact with the environment.
The present work aimed to elucidate how spatial differences in habitat quality affect marine fish populations, with particular focus on spatial variations in population demographics and reproductive output among subpopulations distributed across seascapes. Firstly, I compared demographic parameters, such as the length-frequency distributions, sex ratios, length-at-sex-change, and potential fecundity among five subpopulations of blue cod (Parapercis colias) in the Marlborough Sounds and Tasman Bay (Chapter 2). Secondly, I used stable isotopic values and stomach contents of blue cod subpopulations to investigate the effect of long-term trawling and dredging in Tasman Bay on the trophic niche of blue cod compared to subpopulations inhabiting biogenic reefs in the Marlborough Sounds (Chapter 3). Thirdly, I inferred population structure and movement from multivariate trace element signatures of otoliths from blue cod subpopulations within and among the Marlborough Sounds and Tasman Bay (Chapter 4). To investigate the contribution to the reproductive output and success of individuals within a population, I used proxies for larval fitness and viability to compare cohorts of larvae produced by different aged and sized female sea perch (Helicolenus percoides) (Chapter 5). Lastly, I explored the effect of maternal nutrition, inferred by fatty acid biomarkers, on larval traits on the day of parturition and larval viability and cohorts of larvae produced by female sea perch sampled from two distinct subpopulations from the Otago shelf and Fiordland (Chapter 6).
Three out of the five sampled subpopulations of blue cod from the Marlborough Sounds and Tasman Bay were severely truncated towards a larger proportion of smaller individuals. Sex change, from female to male, occurred at extremely small lengths, resulting in a sex ratio skewed towards a large proportion of small males among four out of five subpopulations. Consequentially, the estimated population batch fecundity was low among these male-dominated subpopulations. Isotopic niches and niche breadths of blue cod subpopulations from the Tasman Bay regions were smaller than those of subpopulations from the Marlborough Sounds. Movement, as inferred by multivariate otolith trace elemental signatures, was low between subpopulations from the Marlborough Sounds and Tasman Bay. However, subpopulations within the Marlborough Sounds likely displayed a source-sink dynamic, where the outer Sounds subpopulation supported the inner Sounds subpopulation with adults. The two subpopulations likely shared a larval source pool.
Older, larger females of sea perch were proportionally more fecund than younger, smaller females. These older, larger females also produced cohorts of larvae with larger oil globules than did younger, smaller females. Cohorts of larvae, with larger oil globules on the day of parturition, had faster growth rates and survived longer in fed treatments, than cohorts of larvae with smaller oil globules. When larval cohorts were compared between subpopulations from the Otago shelf and the inner Fiordland, cohorts produced by females from the Otago shelf had smaller oil globules on the day of parturition than cohorts of larvae produced by females from Fiordland. Among cohorts of larvae produced by females from Fiordland, the concentrations of the essential fatty acids docosahexaenoic acid (DHA) and arachidonic acid (ARA) were higher, and the eicosapentaenoic acid (EPA)/ARA ratio was lower than in cohorts of larvae produced by females from the Otago shelf.
The results of my research indicated that long-term overexploitation in the Marlborough Sounds and Tasman Bay has likely caused sex-change to occur at smaller sizes, resulting in the higher abundance of smaller males, which resulted in lower population fecundity. Smaller trophic niches of blue cod subpopulations from Tasman Bay compared to those of blue cod from the Marlborough Sounds were coincidental with differences in habitat degradation as a result of intensified bottom trawling and dredging within Tasman Bay. Blue cod populations within the Marlborough Sounds showed complex source-sink population structures and likely shared larval source pools, highlighting the importance of considering population structure when designing and implementing management strategies. Older, larger maternal sea perch produced cohorts of larvae that were more viable than those produced by younger, smaller females, emphasising that an old-growth age structure within populations may ensure larval survival and, ultimately, recruitment. Larval viability was not only affected by maternal age and size, but also by maternal nutrition, which resulted in unique visual and osmoregulatory larval adaptations to the low-light, low-productivity environment of the inner Fiordland. Fisheries management should aim to protect population structure, trophic interactions, and critical habitat simultaneously to sustain marine populations effectively
Economic insecurity and income inequality in the wellbeing debate
This thesis explores two key measures of economic wellbeing - economic insecurity and income inequality. Chapters 2 and 3 present an Economic Security Index (ESI) for New Zealand, a new measure of economic wellbeing. An ESI is a measure of economic insecurity that identifies which subgroups of the population are susceptible to financial loss due to events such as an unanticipated rise in medical expenses or a fall in income. An ESI also measures if these subgroups have sufficient financial resources to act as a buffer when economic shocks occur. The main index is constructed in Chapter 2 using micro-level data from New Zealand’s Household Labour Force Survey (HLFS) and Household Economic Survey (HES). An alternative index is constructed in Chapter 3 using longitudinal data from the Survey of Family, Income and Employment (SoFIE) to test the robustness of the main index’s findings. After controlling for various demographic and socioeconomic factors, the findings of both versions of the ESI predict similar patterns. The main findings suggest that economic insecurity is highly cyclical, tracking closely to GDP growth and the unemployment rate. This result suggests that insecurity in New Zealand is largely an involuntary phenomenon. It is also observed that insecurity varies by subgroups of the population. Groups that are more likely to experience economic insecurity are ethnic minorities, young adults, people with no educational qualifications, single-adult households, persons whose relationships ended over the ESI year, high-income households and persons on temporary employment contracts.
In Chapter 4, both versions of the ESI and longitudinal health data from SoFIE are used to estimate the causal impact of economic insecurity on the mental wellbeing of New Zealanders. The study uses fixed effects models to test the hypothesis that being economically insecure increases the likelihood of poor mental wellbeing. To proxy for mental wellbeing, I use each respondent’s Kessler-10 (K10) score as well as the Short Form 36 (SF-36) health survey, two common indicators of mental disorders. For the SF-36 health survey, both the Mental and Physical Component Summary (MCS and PCS) Measures are used. To proxy for insecurity, the exogenously assigned ESI values from HLFS (‘predicted economic insecurity’) are used, as well as ESI values from SoFIE (representing ‘lived insecurity event’, such as if an individual loses their job or gets divorced). Consistent with the literature on this topic, the results suggest that both measures of insecurity lead to worse mental wellbeing; however, the results are not statistically significant. Further, the analysis produced mixed results when looking at the relationship between insecurity and physical health. Experiencing a ‘lived insecurity event’ is found to improve physical wellbeing, albeit the results are not statistically significant. ‘Predicted economic insecurity’ is found to have a strong, statistically significant negative relationship with each respondent’s standardised PCS scores, which suggests that insecurity worsens physical wellbeing. These associations remain after adjusting for several demographic and socioeconomic characteristics.
In Chapter 5, the theme shifts to income inequality. This chapter uses ordinary least squares (OLS) regression analysis to determine the deep determinants of income inequality, a topic that has received very little attention in the literature. Specifically, the study explores whether the deep determinants of comparative development - which explains differences across countries - are also important in explaining within-country income inequality. The three main hypotheses that explain comparative development are the geography, institutions and genetics/fractionalization hypotheses. The results of the preferred model show that there are some elements from each of the three hypotheses that contribute to explaining within-country income inequality. Whether a country is landlocked or not, distance from the technological frontier, birthplace diversity and the time that has elapsed since the Neolithic Revolution are all found to be deep determinants of income inequality. The results also show that the deep determinants of income inequality vary depending on a country’s level of economic development. Explanations for each finding are discussed
Zealandia's deep earth noble and crucial metal endowment; Au, PGE, Ni, Co, Zn, and Cu in exposed mantle rock
Noble metals – Au, Pd, Pt, Rh, Ru, Ir and Os – and crucial metals – here constrained to Ni, Co, Zn and Cu – are critical metal resources utilised in the innovation of green energy production, a paramount technological advancement for today’s warming world. While primary extractable concentrations of noble and crucial metals unequivocally reside in ore deposits, Earth’s mantle is an important reservoir for metal retention and replenishment. Processes modifying the deep Earth should, therefore, lead to certain geological settings becoming more favourably endowed than others. As such, the residence and geochemical behaviours of noble and crucial metals in mantle rock needs to be defined.
Zealandia and its surrounding ocean basins uniquely host an array of exposed deep Earth ultramafic bodies, denoting it as an ideal location for this study. Utilising a diverse suite of local continental (SCLM xenoliths) and oceanic (OLM ophiolite and ocean exposure) ultramafic rocks, this thesis analyses peridotites, orthopyroxenites, chromitites and serpentinites at varying degrees of melt depletion, chemical enrichment and alteration. Synthesising whole rock chemistry with scanning electron microscopy (SEM) mineral chemistry and imaging, laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS) spot analyses, and X-ray fluorescence microscopy (XFM) in- situ element mapping, informs the investigation into the abundance, residence and mobilising mechanisms of noble and crucial metals in Zealandia’s ultramafic rocks from the whole rock to elemental scale.
Crucial metals are found to occur in higher concentrations in OLM rocks than in SCLM xenoliths, despite recording histories of more melt depletion and less metasomatic re-enrichment. Maximum whole rock crucial metal values are: 2900 ppm Ni (dunite), 213 ppm Co (chromitite), 280 ppm Zn (chromitite), and 230 ppm Cu (serpentinite). Observed sulphides and alloys are primarily crucial metal-rich, predominantly occurring as species within the Ni-Fe-Cu system, and commonly include ancillary Co. There are no observed occurrences of Co-dominant phases, and Zn-rich sulphides are only found in S-elevated serpentinites. In addition to presenting as the dominant constituent of mantle metallic phases, the Ni budget is intimately tied to olivine abundance, with an average SEM analysis of 0.3 wt% Ni residing in the olivine crystal lattice. Cobalt and zinc trend well with whole rock iron abundance and are found to occur in Cr-rich spinel phases, and in conjunction with iron exsolution in highly serpentinised samples. Copper does not significantly occur within silicates or spinel, but Cu-metallic phases tend to be spatially associated with OPX grains.
Like crucial metals, noble metals measure higher whole rock abundances in OLM rocks compared to SCLM xenoliths. Primary ophiolitic peridotites are shown to be noble metal enriched, and chromitite cumulates, despite reporting (Pd/Ir)N enrichment indices <1 (indicating PGE depletion), host the highest concentrations of Au and PGE (except for Pd), and are particularly IPGE-rich. Maximum whole rock noble metal values are: 4.92 ppb Au (chromitite), 29.01 ppb Pd (serpentinite), 29.73 ppb Pt (chromitite), 40.25 ppb Rh (chromitite), 750.58 ppb Ru (chromitite), 268.37 ppb Ir (chromitite), and 297.29 ppb Os (chromitite). Observable noble metal-rich sulphides and alloys, predominantly occurring as laurite (RuS2) or IPGE-rich alloys, are only observed in OLM rocks, with chromitites hosting the highest abundance. XFM element mapping suggests that noble metals additionally reside within Cr-rich spinel phases. No Au-rich metallic phases occur coarse enough for measurement; however, LA-ICP-MS spot analyses suggest that Au is occurring as discreet mineral inclusions. Furthermore, data may suggest that the Au budget correlates with PGE enrichment, but whole rock Au was not found to display significant quantifiable behavioural relationships with any other element or geochemical variable investigated in this study.
Data collected here suggest that carbonatite metasomatism may have a significant influence on the PGE budget of SCLM rocks, but there is no evidence to suggest that this affects Au or the crucial metals. Serpentinisation is shown to highly mobilise both noble and crucial metals, often concentrating metal budgets and altering element residence preferences from host silicate and spinel phases to coarse sulphides and/or alloys. Extensive serpentinisation is associated with an influx of sulphur and a relative elevation in incompatible metals: Au, Pd, and Cu. Melt removal is an effective mechanism for mobilising noble and crucial metals, particularly the incompatible elements. Additionally, melt interaction, like that which produces chromitite formations, is remarkably effective at promoting the retention of noble metals, especially IPGE
Inhaled rifampicin powder formulations and their in vivo studies for clinical application in tuberculosis treatment
Background
Tuberculosis (TB), a global health problem caused by Mycobacterium tuberculosis, mainly affects the lungs and spreads to other organs. Rifampicin is a potent anti-TB drug, but its oral delivery results in low drug concentrations in the caseating lung lesions, affecting its bactericidal activity that may lead to treatment failure, relapse and emergence of bacterial resistance. To increase the drug concentration in the lung lesions and the systemic circulation, high-dose rifampicin has been tested clinically via the oral route. However, high oral doses of rifampicin are associated with increased risk of systemic toxicity. Pulmonary delivery is a promising alternative to achieve high drug concentration in the lungs as well as the systemic circulation using lower doses compared to the oral route.
Purpose
The work described in this thesis was aimed at development of high-dose rifampicin powder formulations for inhaled anti-TB therapy, their in vitro characterization, and in vivo assessment of safety and pharmacokinetics after intra-tracheal administration in a rat model. We hypothesized that intra-tracheal administration of high-dose powder formulations of rifampicin would be safe to rat lungs and the liver, and result in higher systemic bioavailability compared to the oral administration at same dose.
Methods
High-dose powder formulations of rifampicin for inhalation were prepared using spray drying and crystallization methods. X-ray powder diffraction (XRD) was used to determine the crystallinity of the powders. A next generation impactor (NGI) was used to study the in vitro aerosolization behaviour. In vitro dissolution test was performed using a custom-made apparatus.
The in vivo safety and pharmacokinetics of high-dose intra-tracheal rifampicin was studied in Sprague Dawley rats. High-dose rifampicin was administered by either intra-tracheal powder insufflation (25 and 50 mg/kg) or oral gavage (50 mg/kg). Following single and repeated administration of rifampicin, safety to rat lung and liver was evaluated by histopathology. Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) assays were performed to study the hepatic effects. For pharmacokinetic evaluation, rifampicin quantification in plasma was carried out by liquid chromatography mass spectrometry (LC-MS/MS) at predetermined time points after drug administration on day 0 and day 6.
Results
Spray drying yielded amorphous powder formulation of rifampicin (RIF A) while crystalline pentahydrate (RIF C1 and RIF C2) and dihydrate (RIF C3) powder formulations were obtained by crystallization. All formulations had a mean particle size smaller than 3.8 μm and a fine particle fraction higher than 58.0%. RIF A and RIF C3 were selected for in vivo studies due to their rapid in vitro dissolution compared to RIF C1 and RIF C2. Intra-tracheal administration of rifampicin resulted in significantly lower serum ALT activity and similar AST activity compared to oral administration, suggesting reduced drug burden on the liver after pulmonary administration. Repeated intra-tracheal administration of rifampicin was well tolerated by rats, and the lung and hepatic architecture was normal upon histopathological evaluation. Rifampicin bioavailability after intra-tracheal RIF A (AUC0-∞ = 193.1 ± 37.9 μg.h/mL) was significantly higher compared to that from its oral administration (AUC0-∞ = 87.4 ± 64.7 μg.h/mL) at same dose. Increasing the intra-tracheal dose resulted in a more than dose proportional bioavailability suggesting nonlinear pharmacokinetics of inhaled rifampicin.
Conclusions
The amorphous and the crystalline dihydrate rifampicin formulations are suitable for inhaled high-dose delivery of rifampicin in TB treatment. A high concentration of rifampicin in the lungs and the systemic circulation at a relatively low administered dose can be achieved by pulmonary administration of rifampicin, either alone or in addition to the standard oral dose. By achieving high bioavailability of rifampicin, this approach has the potential to achieve improved bactericidal activity, minimize the development of drug resistance and reduce the duration of TB treatment
NZDep2018 analysis of census 2018 variables - DHB01: Northland
For further information about data sources, interpretation of the graphs, and cautions, please see the separate Introduction Chapter
All data relating to the 2018 census is provided by Stats NZ, https://www.stats.govt.nz/
NZDep2018 analysis of census 2018 variables - DHB11: Whanganui
For further information about data sources, interpretation of the graphs, and cautions, please see the separate Introduction Chapter
All data relating to the 2018 census is provided by Stats NZ, https://www.stats.govt.nz/