How is enrolment with a general practice associated with subsequent use of the emergency department in Aotearoa New Zealand? A cohort study.

Introduction Around 5% of the people in Aotearoa New Zealand (NZ) are not enrolled with a general practice. Aim This study aimed to explore the utilisation of general practice by enrolment status and subsequent use of an emergency department. Methods We compared a cohort of respondents from New Zealand Health Surveys (2013/14-2018/19) on self-reported general practice utilisation and their substitutes, according to their enrolment status (enrolled and not enrolled). They were then followed up to examine their subsequent use of an emergency department. Time to an emergency department presentation was modelled with proportional hazards regression models with enrolment status as the explanatory variable. Confounding variables used were sex, age group, prioritised ethnicity, the New Zealand Deprivation Index and self-rated health. Results Those not enrolled were more likely to be young, male, Asian, more socioeconomically deprived and with better health status than those enrolled. Generally, those not enrolledutilised general practice services less. Those not enrolled who had used an emergency department were more likely to have used it as a substitute for general practice (40% vs 26%). Modelling showed that those not enrolled took longer to access an emergency department. Adjusting for confounding variables did not change that interpretation. Discussion Those not enrolled were younger and healthier and may have a perception that enrolment isn't necessary. As a group, they were more likely to be socioeconomically deprived and to use an emergency department, which is free at a public hospital in NZ, as a substitute for primary care which suggests that cost may influence their choices.

An area-based analysis of general practice fees in Aotearoa New Zealand.

Introduction The pursuit of health care equity is a fundamental objective for Aotearoa New Zealand, and patient co-payments in primary care challenge this goal. Aim This study aimed to investigate the relationship between primary health care co-payments and the sociodemographic variables in areas where general practices provide health care. Methods Using census data, facilities information from the Ministry of Health, and socioeconomic deprivation indices, linear regression models were used to explore the relationship between weighted average fees charged by general practices and various sociodemographic variables in statistical area 2 regions. Results The study finds that areas with higher proportions of males and economically deprived individuals are associated with lower weighted average fees. Conversely, areas with higher proportions of retirement-aged and European individuals are linked with higher weighted average fees. The inclusion of the Very-Low-Cost-Access variable, indicating a subsidy scheme at the general practice level, made all the sociodemographic variables practically insignificant, suggesting Very-Low-Cost-Access practices are in the right geographical location to target high needs groups. Discussion The findings affirm the complexity of health care inequities in Aotearoa New Zealand, influenced not only by financial factors but also by demographic variables as they play out geographically. While subsidy schemes like the Very-Low-Cost-Access scheme appear to reach groups with greater need, a high level of unmet need due to cost suggests that the fees are still too high. Policymakers need to consider disparities in the on-going health care reforms and make further changes to subsidy schemes to reduce unmet need.

Consequences of cost barriers to prescriptions: cohort study in Aotearoa New Zealand.

AIMS: A NZ$5 co-payment prescription charge was removed in July 2023 but may be reinstated. Here we quantify the health impact and cost of not being able to afford this charge. METHODS: We linked New Zealand Health Surveys (2013/2014-2018/2019) to hospitalisation data using data available in Integrated Data Infrastructure (IDI). Cox proportional-hazards models compared time to hospitalisation between those who had faced a cost barrier to collecting a prescription and those who had not. RESULTS: Of the 81,626 total survey respondents, 72,243 were available for analysis in IDI. A further 516 were excluded to give an analysis dataset of 71,502. Of these, 5,889 (8.2%) reported not collecting a prescription due to cost in the previous year. Among people who faced a cost barrier, 60.0% (95% confidence interval [CI] 58.7-61.2%) were admitted to hospital during the study period, compared to 43.9% (95% CI 43.6-44.3%) of those who did not. Having adjusted for socio-demographic variables, people who faced a cost barrier were 34% (hazard ratio 1.34; 95% CI 1.29-1.39) more likely to be admitted to hospital than those who did not. Annual avoidable hospitalisation costs-were prescription co-payments to remain free-are estimated at $32.4 million per year based on the assumption of a causal relationship between unmet need for prescription medicines and subsequent hospitalisation. CONCLUSIONS: The revenue to the health system from co-payments may be offset by the costs associated with avoidable hospitalisations.

Building a systems-thinking community workforce to scale action on determinants of health in New Zealand.

This article describes findings from the evaluation of Healthy Families NZ (HFNZ), an equity-driven, place-based community health initiative. Implemented in nine diverse communities across New Zealand, HFNZ aims to strengthen the systems that can improve health and well-being. Findings highlight local needs and priorities including the social mechanisms important for reorienting health and policy systems towards place-based communities. Lessons encompass the importance of local lived experience in putting evidence into practice; the strength of acting with systems in mind; the need for relational, learning, intentional, and well-resourced community organisation; examples of how to foster place-based 'community-up' leadership; and how to enable responsiveness between communities and local and national policy systems. A reconceptualisation of scaling in the context of complexity and systems change is offered, which recognises that relationships and agency are key to making progress on the determinants of health.

"Closed books": restrictions to primary healthcare access in Aotearoa New Zealand-reporting results from a survey across general practices.

AIM: In Aotearoa New Zealand, primary care is organised by enrolling patients with a primary care provider. However, the benefits of this arrangement are frustrated when providers "close their books" due to insufficient capacity for new patients. We investigated the extent, evolution and impact of this situation on health access and equity in access to primary healthcare. METHOD: We distributed a survey for general practice personnel in 2022, yielding 227 valid responses. We examined responses across respondents' practice characteristics, including practice size, rural-urban setting, average co-payments, region and ethnic composition of the catchment population. RESULTS: Most general practices are selectively enrolling their patients. In 2022, only 28% of respondents freely enrolled new people. Since 2019, most respondents (79%) had "closed books" or limited enrolments at some point. The situation worsened between 2019 and 2022, compromising equal opportunity and access in healthcare. CONCLUSION: Restricted enrolment poses a widespread barrier to health access and equity, and it worsened since the beginning of the COVID-19 pandemic. Addressing closed books and limited enrolments in general practice could significantly improve health services' access and equity. The study aims to inform ongoing health reforms.

The enrolment gap and the COVID-19 pandemic: an exploration of routinely collected primary care enrolment data from 2016 to 2023 in Aotearoa New Zealand.

Introduction For many countries, primary health care (PHC) serves as the gateway for individuals to access healthcare services. It has been shown to not only improve health but also health equity. To maximise this benefit, a substantial proportion of the population needs to be connected with PHC. The aim here was to assess the degree and evolution of enrolment in light of the coronavirus disease 2019 (COVID-19) pandemic in Aotearoa New Zealand. Methods We examined data on the enrolment of people in PHC organisations between 2016 and 2023. This analysis included breakdowns by sex, age groups, ethnicity, and socioeconomic deprivation levels. Poisson regression models were used to explore whether enrolment changed because of the COVID-19 pandemic. Results In 2016, Maori, young people and the most deprived had lower enrolment rates relative to their peers. Although young people's enrolment rate increased over time, especially during the COVID-19 pandemic, the Maori enrolment rate declined, as did the rate for Pacific people, and those who were the most deprived. The groups who had increases in enrolment rates were those with the lowest levels of socioeconomic deprivation and those in the 'Other' ethnic category, predominantly made up of European New Zealanders. Conclusion Enrolment statistics reveal disparities across sociodemographic lines. The COVID-19 pandemic was associated with changed patterns of enrolment that appear to have consequences for population health.

Financial barriers to primary health care in Aotearoa New Zealand.

BACKGROUND: In Aotearoa New Zealand, co-payments to see a general practitioner (GP, family doctor) or collect a prescription are payable by virtually all adults. OBJECTIVE: To examine the extent to which these user co-payments are a barrier to accessing health care, focussing on inequities for indigenous Maori. METHODS: Pooled data from sequential waves (years) of the New Zealand Health Survey, 2011/12 to 2018/19 were analysed. Outcomes were self-reported cost barriers to seeing a GP or collecting a prescription in the previous year. Logistic regression was used to estimate odds ratios (ORs) of barriers to care for Maori compared with non-Maori, sequentially adjusting for additional explanatory variables. RESULTS: Pooled data included 107,231 people, 22,292 (21%) were Maori. Across all years, 22% of Maori (13% non-Maori) experienced a cost barrier to seeing a GP, and 14% of Maori (5% non-Maori) reported a cost barrier to collecting a prescription. The age- and wave-adjusted OR comparing Maori/non-Maori was 1.71 (95% confidence interval [CI]: 1.61, 1.81) for the cost barrier to primary care and 2.97 (95% CI: 2.75, 3.20) for the cost barrier to collecting prescriptions. Sociodemographics accounted for about half the inequity for both outcomes; in a fully adjusted model, age, sex, low income, and poorer underlying health were determinants of both outcomes, and deprivation was additionally associated with the cost barrier to collecting a prescription but not to seeing a GP. CONCLUSIONS: Maori experience considerable inequity in access to primary health care; evidence supports an urgent need for change to system funding to eliminate financial barriers to care.

Cohort profile: Nga Kawekawe o Mate Korona | Impacts of COVID-19 in Aotearoa - a prospective, national cohort study of people with COVID-19 in New Zealand.

PURPOSE: The COVID-19 pandemic has had significant health, social and economic impacts around the world. We established a national, population-based longitudinal cohort to investigate the immediate and longer-term physical, psychological and economic impacts of COVID-19 on affected people in Aotearoa New Zealand (Aotearoa), with the resulting evidence to assist in designing appropriate health and well-being services for people with COVID-19. PARTICIPANTS: All people residing in Aotearoa aged 16 years or over, who had a confirmed or probable diagnosis of COVID-19 prior to December 2021, were invited to participate. Those living in dementia units were excluded. Participation involved taking part in one or more of four online surveys and/or in-depth interviews. The first wave of data collection took place from February to June 2022. FINDINGS TO DATE: By 30 November 2021, of 8735 people in Aotearoa aged 16+ who had COVID-19, 8712 were eligible for the study and 8012 had valid addresses so were able to be contacted to take part. A total of 990 people, including 161 Tangata Whenua (Maori, Indigenous peoples of Aotearoa) completed one or more surveys; in addition, 62 took part in in-depth interviews. Two hundred and seventeen people (20%) reported symptoms consistent with long COVID. Key areas of adverse impacts were experiences of stigma, mental distress, poor experiences of health services and barriers to healthcare, each being significantly more pronounced among disabled people and/or those with long COVID. FUTURE PLANS: Further data collection is planned to follow-up cohort participants. This cohort will be supplemented by the inclusion of a cohort of people with long COVID following Omicron infection. Future follow-ups will assess longitudinal changes to health and well-being impacts, including mental health, social, workplace/education and economic impacts of COVID-19.

An area-based description of closed books in general practices in Aotearoa New Zealand.

Introduction In Aotearoa New Zealand, patients can enrol in a general practice for their primary health care. When a general practice no longer enrols new patients this is known as 'closed books'. We examined which District Health Board (DHB) districts were most affected and what characteristics of general practices and DHB districts were associated with closed books. Methods Maps were used to display the distribution of closed books general practices. Linear regression and logistic regression were used to look at the association between DHB or general practice characteristics and closed books. Results There were 347 (33%) general practices that had closed books in June 2022. Canterbury DHB (n = 45) and Southern DHB (n = 32) had the greatest number of closed books general practices, while Wairarapa DHB (86%), Midcentral DHB (81%) and Taranaki DHB (81%) had the greatest percentage. Consultation fees (P Conclusion The problem of closed books is felt across the country but has a larger impact in the middle-lower North Island. This influences access to primary health care enrolment for patients in terms of travel distance, time, and cost. Consultation fees were strongly associated with closed books. This suggests there may be an income threshold above which general practices can afford to close their books if they reach capacity.

Biomedical Applications of Lactoferrin on the Ocular Surface.

Lactoferrin (LF) is a first-line defense protein with a pleiotropic functional pattern that includes anti-inflammatory, immunomodulatory, antiviral, antibacterial, and antitumoral properties. Remarkably, this iron-binding glycoprotein promotes iron retention, restricting free radical production and avoiding oxidative damage and inflammation. On the ocular surface, LF is released from corneal epithelial cells and lacrimal glands, representing a significant percentage of the total tear fluid proteins. Due to its multifunctionality, the availability of LF may be limited in several ocular disorders. Consequently, to reinforce the action of this highly beneficial glycoprotein on the ocular surface, LF has been proposed for the treatment of different conditions such as dry eye, keratoconus, conjunctivitis, and viral or bacterial ocular infections, among others. In this review, we outline the structure and the biological functions of LF, its relevant role at the ocular surface, its implication in LF-related ocular surface disorders, and its potential for biomedical applications.

Association between enrolment with a Primary Health Care provider and amenable mortality: A national population-based analysis in Aotearoa New Zealand.

INTRODUCTION: In Aotearoa New Zealand, being enrolled with a Primary Health Care (PHC) provider furnishes opportunities for lower cost access to PHC, preventative care and secondary health care services, and provides better continuity of care. We examine the characteristics of populations not enrolled, and whether enrolment is associated with amenable mortality. METHOD: We retrieved records of all deaths registered 2008 to 2017 in Aotearoa New Zealand, which included demographic and primary cause of death information. Deaths were classified as premature (aged under 75 years) or not, and amenable to health care intervention or not. The Primary Health Organisation (PHO) Enrolment Collection dataset provided the PHC enrolment status. Logistic regression was used to estimate the risk of amenable deaths by PHO enrolment status, adjusted for the effects of age, sex, ethnicity and deprivation. RESULTS: A total of 308,628 mortality records were available. Of these, 38.2% were premature deaths, and among them 47.8% were amenable deaths. Cardiovascular diseases made up almost half of the amenable deaths. Males, youths aged 15-24 years, Pacific peoples, Maori and those living in the most socio-economically deprived areas demonstrated a higher risk of amenable mortality compared to their respective reference category. One in twenty (4.3%) people who had died had no active enrolment status in any of the calendar years in the study. The adjusted odds of amenable mortality among those not enrolled in a PHO was 39% higher than those enrolled [Odds Ratio = 1.39, 95% Confidence Interval 1.30-1.47]. IMPLICATIONS: Being enrolled in a PHC system is associated with a lower level of amenable mortality. Given demonstrated inequities in enrolment levels across age and ethnic groups, efforts to improve this could have significant benefits on health equity.

Immunomodulatory Effect of Human Lactoferrin on Toll-like Receptors 2 Expression as Therapeutic Approach for Keratoconus.

Keratoconus (KC) is a corneal disorder whose etiology shares a close relationship with Lactoferrin (LTF) dysregulation and Toll-like Receptors 2 (TLR2) overexpression. This study shows how these two important biomarkers are clinically and molecularly interrelated, increasing knowledge about KC pathophysiology, and opening the door to future therapies. In this prospective clinical study, serum and tear LTF concentrations were quantified in 90 KC patients and 60 controls. A correlation analysis with multiple blood and tear immunoinflammatory mediators, and KC-associated tomographic parameters, was performed. An in vitro study using HEK-BlueTMhTLR2 cell cultures was also conducted to determine the expression and functionality of TLR2 under the influence of LTF treatment. As a result, a LTF decreased was observed in KC patients compared to controls (p < 0.0001), evidencing the strong correlation with TLR2 overexpression at systemic and ocular surface level, with inflammatory mediator upregulation and with KC severity. In stimulated cell cultures, TLR2 expression was decreased using 2 mg/mL of LTF. The levels of secreted embryonic alkaline phosphatase (SEAP) and interleukin-8 (IL-8) were also reduced in supernatants after LTF treatment. As conclusions, the dysregulation of LTF and TLR2 in the ocular surface of KC patients contributes to KC severity by maintaining a detrimental chronic immune−inflammatory state. The immunomodulatory properties of LTF on TLR2 expression suggest its potential as a therapeutic approach for KC.

Molecular Oncology of Bladder Cancer from Inception to Modern Perspective.

Within the last forty years, seminal contributions have been made in the areas of bladder cancer (BC) biology, driver genes, molecular profiling, biomarkers, and therapeutic targets for improving personalized patient care. This overview includes seminal discoveries and advances in the molecular oncology of BC. Starting with the concept of divergent molecular pathways for the development of low- and high-grade bladder tumors, field cancerization versus clonality of bladder tumors, cancer driver genes/mutations, genetic polymorphisms, and bacillus Calmette-Guérin (BCG) as an early form of immunotherapy are some of the conceptual contributions towards improving patient care. Although beginning with a promise of predicting prognosis and individualizing treatments, "-omic" approaches and molecular subtypes have revealed the importance of BC stem cells, lineage plasticity, and intra-tumor heterogeneity as the next frontiers for realizing individualized patient care. Along with urine as the optimal non-invasive liquid biopsy, BC is at the forefront of the biomarker field. If the goal is to reduce the number of cystoscopies but not to replace them for monitoring recurrence and asymptomatic microscopic hematuria, a BC marker may reach clinical acceptance. As advances in the molecular oncology of BC continue, the next twenty-five years should significantly advance personalized care for BC patients.

Shotgun Proteomics for the Identification and Profiling of the Tear Proteome of Keratoconus Patients.

Purpose: The qualitative approach followed in this study aims to obtain an extensive view of the keratoconus (KC) tear proteome, which could highlight proteins previously undetected and enlarge our knowledge of the disease's pathophysiology. Methods: Twenty-five patients diagnosed with KC and 25 control subjects were studied in a prospective, cross-sectional study. KC screening examinations, including clinical and tomographic examinations, were performed on all participants. Tear samples were collected using Schirmer strips and analyzed by liquid chromatography-tandem mass spectrometry in a data-dependent workflow. A spectral count was used as a semiquantification tool. The tear proteomes of both groups were identified and profiled, and the functional interactions and biological characterization of differential proteins were analyzed using in silico tools. Results: We identified a total of 232 proteins, of whom 133 were expressed in both groups' samples; 41 were observed only in control samples and 58 were identified just in tears of patients with KC. A semiquantitative analysis showed the dysregulation of 17 proteins in the KC samples. An in silico analysis linked proteins only expressed in KC samples to oxidative stress, skin development, and apoptosis. The dysregulation of proteins involved in iron transport, inflammation, oxidative stress, and protease inhibition was observed in the semiquantitative results. Conclusions: A shotgun analysis showed that the tear proteome of patients with KC differed from controls by more than one-third of the total proteins identified, highlighting the relationship of the proteins only expressed in KC tears with processes of cell death, oxidative damage, and inflammation. The underexpression of proteins involved in iron pathways might support the iron imbalance as a contributing factor to cellular damage and death in KC disease.

Mucoadhesive PLGA Nanospheres and Nanocapsules for Lactoferrin Controlled Ocular Delivery.

BACKGROUND: the present work describes the preparation, characterization and optimization of eight types of PLGA-based nanosystems (nanospheres and nanocapsules) as innovative mucoadhesive drug delivery systems of lactoferrin, in order to achieve a preclinical consistent base as an alternative pharmacological treatment to different ocular syndromes and diseases. METHODS: All different nanoparticles were prepared via two modified nanoprecipitation techniques, using a three-component mixture of drug/polymer/surfactant (Lf/PLGA/Poloxamer), as a way to overcome the inherent limitations of conventional PLGA NPs. These modified polymeric nanocarriers, intended for topical ophthalmic administration, were subjected to in vitro characterization, surface modification and in vitro and in vivo assessments. RESULTS: An appropriate size range, uniform size distribution and negative ζ potential values were obtained for all types of formulations. Lactoferrin could be effectively included into all types of nanoparticles with appropriate encapsulation efficiency and loading capacity values. A greater, extended, and controlled delivery of Lf from the polymeric matrix was observed through the in vitro release studies. No instability or cytotoxicity was proved for all the formulations by means of organotypic models. Additionally, mucoadhesive in vitro and in vivo experiments show a significant increase in the residence time of the nanoparticles in the eye surface. CONCLUSIONS: all types of prepared PLGA nanoparticles might be a potential alternative for the topical ophthalmic administration of lactoferrin.

Alzheimer's Disease Seen through the Eye: Ocular Alterations and Neurodegeneration.

Alzheimer's Disease (AD) is one of the main neurodegenerative diseases worldwide. Unfortunately, AD shares many similarities with other dementias at early stages, which impedes an accurate premortem diagnosis. Therefore, it is urgent to find biomarkers to allow for early diagnosis of the disease. There is increasing scientific evidence highlighting the similarities between the eye and other structures of the CNS, suggesting that knowledge acquired in eye research could be useful for research and diagnosis of AD. For example, the retina and optic nerve are considered part of the central nervous system, and their damage can result in retrograde and anterograde axon degeneration, as well as abnormal protein aggregation. In the anterior eye segment, the aqueous humor and tear film may be comparable to the cerebrospinal fluid. Both fluids are enriched with molecules that can be potential neurodegenerative biomarkers. Indeed, the pathophysiology of AD, characterized by cerebral deposits of amyloid-beta (Aß) and tau protein, is also present in the eyes of AD patients, besides numerous structural and functional changes observed in the structure of the eyes. Therefore, all this evidence suggests that ocular changes have the potential to be used as either predictive values for AD assessment or as diagnostic tools.

Selective vulnerability of tripartite synapses in amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder. Separate lines of evidence suggest that synapses and astrocytes play a role in the pathological mechanisms underlying ALS. Given that astrocytes make specialised contacts with some synapses, called tripartite synapses, we hypothesise that tripartite synapses could act as the fulcrum of disease in ALS. To test this hypothesis, we have performed an extensive microscopy-based investigation of synapses and tripartite synapses in the spinal cord of ALS model mice and post-mortem human tissue from ALS cases. We reveal widescale synaptic changes at the early symptomatic stages of the SOD1G93a mouse model. Super-resolution microscopy reveals that large complex postsynaptic structures are lost in ALS mice. Most surprisingly, tripartite synapses are selectively lost, while non-tripartite synapses remain in equal number to healthy controls. Finally, we also observe a similar selective loss of tripartite synapses in human post-mortem ALS spinal cords. From these data we conclude that tripartite synaptopathy is a key hallmark of ALS.

Lactoferrin-loaded nanostructured lipid carriers (NLCs) as a new formulation for optimized ocular drug delivery.

Nanostructured lipid carriers (NLC) are novel lipidic nanosystems that provide significant improvements in terms of high drug loading capacity and controlled drug release. The purpose of the present work was based on the design, development, and physicochemical characterization of lactoferrin-loaded NLCs as a new therapeutic alternative for the keratoconus treatment. Lactoferrin-loaded NLCs were successfully prepared by a double emulsion/solvent evaporation method. The resultant NLC were assessed in terms of particle size, size distribution, surface charge, morphology, encapsulation efficiency (EE), loading capacity (LC), stability, cytotoxicity, in vitro release, and ocular surface retention. Resulting data showed a size of 119.45 ± 11.44 nm, a 0.151 ± 0.045 PDI value and a surface charge of -17.50 ± 2.53 mV. Besides, high EE and LC values were obtained (up to 75%). The in vitro release study demonstrated a lactoferrin controlled release pattern. NLCs were also stable, non-toxic and show mucoadhesive properties. Thus, a consistent preclinical base was obtained, where NLC may be considered as a potential controlled release novel drug delivery system of lactoferrin for the keratoconus treatment.

Assessing need for primary care services: analysis of New Zealand Health Survey data.

Introduction The 2001 Primary Health Care Strategy provided significant new government funding for primary care (general practice and related services) via capitation funding formulas. However, there remain important unanswered questions about how capitation funding formulas should be redesigned to ensure equitable and sustainable service provision to all population groups. Aim To compare levels of chronic illness, utilisation, and unmet need in patients categorised as 'high-need' with those categorised as non-'high-need' using the definitions that are used in the current funding context, in order to inform primary care funding formula design. Methods Respondents of the New Zealand Health Survey (2018-19) were categorised into 'high-need' and non-'high-need', as defined in current funding formulas. We analysed: (i) presence, and number, of chronic diseases; (ii) self-reported primary care utilisation (previous 12 months); and (iii) self-reported unmet need for primary care (previous 12 months). Analyses used integrated survey weights to account for survey design. Results In total, 29% of respondents were 'high-need', of whom 50.2% reported one or more chronic conditions (vs 47.8% of non-'high-need' respondents). 'High-need' respondents were more likely than non-'high-need' respondents to: report three or more chronic conditions (14.4% vs 13.7%); visit a general practitioner more often (seven or more visits per year: 9.9% vs 6.6%); and report barriers to care. Discussion There is an urgent need for further quantification of the funding requirements of general practices serving high proportions of 'high-need' patients in order to ensure their viability, sustainability and the provision of quality of care.