RESUMEN
AIM: Armed conflict remains a tragic feature of the modern world and so it is necessary to continue to study its health impacts. Even the study of historical conflicts is relevant given that certain health impacts are common to most wars e.g., post-traumatic stress disorder (PTSD). METHODS: This study built on a previous quantitative analysis of a randomly selected group of 200 New Zealand veterans from the First World War (WWI). From this sample we selected 10 cases that illustrated particular themes around morbidity impacts. RESULTS: The theme of severity of impacts was illustrated with a case who was severely wounded and died from suicide when back in New Zealand, and another case with severe PTSD. The theme of the high frequency of non-fatal conditions was revealed with cases illustrating new diagnoses (a case with n=8 diagnoses), hospitalisations for new conditions (n=6), non-fatal injury events (n=3) and for sexually transmitted infections (n=3). The theme of chronic debility as a consequence of various conditions was illustrated with cases who had suffered from being gassed or having gastroenteritis, malaria or pandemic influenza. CONCLUSION: These 10 selected cases reiterate how severe and extensive the morbidity burden for military personnel in WWI could be. Also illustrated is how the morbidity could contribute to adverse impacts on some of their lives after returning to New Zealand.
Asunto(s)
Veteranos , Primera Guerra Mundial , Humanos , Nueva Zelanda/epidemiología , Veteranos/psicología , Masculino , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/psicología , Adulto , Persona de Mediana Edad , Historia del Siglo XXRESUMEN
BACKGROUND: Longitudinal studies have identified childhood asthma as a risk factor for obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO) where persistent airflow limitation can develop more aggressively. However, a causal link between childhood asthma and COPD/ACO remains to be established. Our study aimed to model the natural history of childhood asthma and COPD and to investigate the cellular/molecular mechanisms that drive disease progression. METHODS: Allergic airways disease was established in three-week-old young C57BL/6 mice using house dust mite (HDM) extract. Mice were subsequently exposed to cigarette smoke (CS) and HDM for 8 weeks. Airspace enlargement (emphysema) was measured by the mean linear intercept method. Flow cytometry was utilised to phenotype lung immune cells. Bulk RNA-sequencing was performed on lung tissue. Volatile organic compounds (VOCs) in bronchoalveolar lavage-fluid were analysed to screen for disease-specific biomarkers. RESULTS: Chronic CS exposure induced emphysema that was significantly augmented by HDM challenge. Increased emphysematous changes were associated with more abundant immune cell lung infiltration consisting of neutrophils, interstitial macrophages, eosinophils and lymphocytes. Transcriptomic analyses identified a gene signature where disease-specific changes induced by HDM or CS alone were conserved in the HDM-CS group, and further revealed an enrichment of Mmp12, Il33 and Il13, and gene expression consistent with greater expansion of alternatively activated macrophages. VOC analysis also identified four compounds increased by CS exposure that were paradoxically reduced in the HDM-CS group. CONCLUSIONS: Early-life allergic airways disease worsened emphysematous lung pathology in CS-exposed mice and markedly alters the lung transcriptome.
Asunto(s)
Asma , Fumar Cigarrillos , Enfisema , Hipersensibilidad , Enfisema Pulmonar , Humanos , Animales , Ratones , Ratones Endogámicos C57BL , Pyroglyphidae , Fumar Cigarrillos/efectos adversos , Enfisema Pulmonar/etiología , InflamaciónRESUMEN
Occurrence of cryptosporidiosis has been associated with weather conditions in many settings internationally. We explored statistical clusters of human cryptosporidiosis and their relationship with severe weather events in New Zealand (NZ). Notified cases of cryptosporidiosis from 1997 to 2015 were obtained from the national surveillance system. Retrospective space-time permutation was used to identify statistical clusters. Cluster data were compared to severe weather events in a national database. SaTScan analysis detected 38 statistically significant cryptosporidiosis clusters. Around a third (34.2%, 13/38) of these clusters showed temporal and spatial alignment with severe weather events. Of these, nearly half (46.2%, 6/13) occurred in the spring. Only five (38%, 5/13) of these clusters corresponded to a previously reported cryptosporidiosis outbreak. This study provides additional evidence that severe weather events may contribute to the development of some cryptosporidiosis clusters. Further research on this association is needed as rainfall intensity is projected to rise in NZ due to climate change. The findings also provide further arguments for upgrading the quality of drinking water sources to minimize contamination with pathogens from runoff from livestock agriculture.
Asunto(s)
Criptosporidiosis , Tiempo (Meteorología) , Criptosporidiosis/epidemiología , Nueva Zelanda/epidemiología , Humanos , Estudios Retrospectivos , Adulto , Preescolar , Masculino , Persona de Mediana Edad , Niño , Femenino , Anciano , Adolescente , Adulto Joven , Agrupamiento Espacio-Temporal , Lactante , Brotes de Enfermedades , Anciano de 80 o más Años , Estaciones del Año , Recién NacidoRESUMEN
A major global catastrophe would likely disrupt trade in liquid fuels. Countries dependent on imported oil products might struggle to sustain industrial agriculture. Island nations importing 100% of refined fuels are particularly vulnerable. Our case study aimed to estimate the agricultural land area and biofuel volumes needed to feed the population of New Zealand in the absence of trade. Results showed that stored diesel would quickly be exhausted with ordinary use (weeks) and even with strict rationing (months). To preserve fuel, we found that farming wheat (requiring as little as 5.4 million liters [L] of diesel per annum) was more fuel-efficient than potatoes (12.3) or dairy (38.7) to feed the national population under a climate-as-usual scenario. In a nuclear winter scenario, with reduced agricultural yields, proportionately greater diesel is needed. The wheat would require 24% of current grain-cropped land, and the canola crop used as feedstock for the required biofuel would occupy a further 1%-7%. Investment in canola biodiesel or renewable diesel refineries could ensure supply for the bare minimum agricultural liquid fuel needs. Were subsequent analysis to favor this option as part of a fuels resilience response and as a tradeoff for routine food use, expansion in refining and canola cropping before a catastrophe could be encouraged through market mechanisms, direct government investment, or a combination of these. Logistics of biofuel refining scale-up, post-catastrophe, should also be analyzed. Further, biodiesel produced in normal times would help the nation meet its emissions reduction targets. Other countries should conduct similar analyses.
RESUMEN
BACKGROUND: Patients with severe asthma can present with eosinophilic type 2 (T2), neutrophilic, or mixed inflammation that drives airway remodeling and exacerbations and represents a major treatment challenge. The common ß (ßc) receptor signals for 3 cytokines, GM-CSF, IL-5, and IL-3, which collectively mediate T2 and neutrophilic inflammation. OBJECTIVE: To determine the pathogenesis of ßc receptor-mediated inflammation and remodeling in severe asthma and to investigate ßc antagonism as a therapeutic strategy for mixed granulocytic airway disease. METHODS: ßc gene expression was analyzed in bronchial biopsy specimens from patients with mild-to-moderate and severe asthma. House dust mite extract and Aspergillus fumigatus extract (ASP) models were used to establish asthma-like pathology and airway remodeling in human ßc transgenic mice. Lung tissue gene expression was analyzed by RNA sequencing. The mAb CSL311 targeting the shared cytokine binding site of ßc was used to block ßc signaling. RESULTS: ßc gene expression was increased in patients with severe asthma. CSL311 potently reduced lung neutrophils, eosinophils, and interstitial macrophages and improved airway pathology and lung function in the acute steroid-resistant house dust mite extract model. Chronic intranasal ASP exposure induced airway inflammation and fibrosis and impaired lung function that was inhibited by CSL311. CSL311 normalized the ASP-induced fibrosis-associated extracellular matrix gene expression network and strongly reduced signatures of cellular inflammation in the lung. CONCLUSIONS: ßc cytokines drive steroid-resistant mixed myeloid cell airway inflammation and fibrosis. The anti-ßc antibody CSL311 effectively inhibits mixed T2/neutrophilic inflammation and severe asthma-like pathology and reverses fibrosis gene signatures induced by exposure to commonly encountered environmental allergens.
Asunto(s)
Asma , Receptores de Citocinas , Ratones , Animales , Humanos , Receptores de Citocinas/metabolismo , Remodelación de las Vías Aéreas (Respiratorias) , Pulmón , Citocinas/metabolismo , Ratones Transgénicos , Inflamación , Alérgenos , Esteroides/uso terapéutico , Fibrosis , PyroglyphidaeRESUMEN
Excess winter mortality (EWM) has been used as a measure of how well populations and policy moderate the health effects of cold weather. We aimed to investigate long-term changes in the EWM of Aotearoa New Zealand (NZ), and potential drivers of change, and to test for structural breaks in trends. We calculated NZ EWM indices from 1876 (4,698 deaths) to 2020 (33,310 deaths), total and by age-group and sex, comparing deaths from June to September (the coldest months) to deaths from February to May and October to January. The mean age and sex-standardised EWM Index (EWMI) for the full study period, excluding 1918, was 1.22. However, mean EWMI increased from 1.20 for 1886 to 1917, to 1.34 for the 1920s, then reduced over time to 1.14 in the 2010s, with excess winter deaths averaging 4.5% of annual deaths (1,450 deaths per year) in the 2010s, compared to 7.9% in the 1920s. Children under 5 years transitioned from a summer to winter excess between 1886 and 1911. Otherwise, the EWMI age-distribution was J-shaped in all time periods. Structural break testing showed the 1918 influenza pandemic strain had a significant impact on trends in winter and non-winter mortality and winter excess for subsequent decades. It was not possible to attribute the post-1918 reduction in EWM to any single factor among improved living standards, reduced severe respiratory infections, or climate change.
Asunto(s)
Frío , Gripe Humana , Niño , Humanos , Preescolar , Nueva Zelanda/epidemiología , Estaciones del Año , Cambio Climático , MortalidadRESUMEN
BACKGROUND: Aotearoa-New Zealand (A/NZ) was the first country to pass a comprehensive commercial tobacco endgame strategy into law. Key components include the denicotinisation of smoked tobacco products and a major reduction in tobacco retail outlets. Understanding the potential long-term economic impacts of such measures is important for government planning. DESIGN: A tobacco policy simulation model that evaluated the health impacts of the A/NZ Smokefree Action Plan was extended to evaluate the economic effects from both government and citizen perspectives. Estimates were presented in 2021 US$, discounted at 3% per annum. RESULTS: The modelled endgame policy package generates considerable growth in income for the A/NZ population with a total cumulative gain of US$31 billion by 2050. From a government perspective, increased superannuation payments and reduced tobacco excise tax revenue result in a negative net financial position and a cumulative shortfall of US$11.5 billion by 2050. In a sensitivity analysis considering future labour force changes, the government's cumulative net position remained negative by 2050, but only by US$1.9 billion. CONCLUSIONS: A policy such as the A/NZ Smokefree Action Plan is likely to produce substantial economic benefits for citizens, and modest impacts on government finances related to reduced tobacco tax and increases in aged pensions due to increased life expectancy. Such costs can be anticipated and planned for and might be largely offset by future increases in the size of the labour force and the proportion of people 65+ years old working in the formal economy.
RESUMEN
AIMS: Studies of the morbidity burden of military personnel participating in the First World War (WWI) have tended to focus on specific outcomes (e.g., injuries). Therefore, we aimed for a more complete assessment. METHODS: From a random sample of active war service-exposed New Zealand WWI veterans used in previously published work, we examined a random subsample of 200 personnel. Data on diagnoses, hospitalisations and outcomes were extracted from the online archival military files. RESULTS: These personnel experienced a very high morbidity burden with 94% having at least one new condition diagnosed during their military service (mean: 2.4 per individual; range: 0 to 8). The relative severity of these conditions was reflected by the high level of hospitalisation (89% at least once; mean: 1.8 hospitalisations for new conditions per individual) and 59% of personnel being deemed no longer fit for military service at some stage. More of the new diagnoses were for infectious diseases than for conflict-related injuries (117 vs 50 cases per 100 personnel). Respiratory conditions such as influenza, pneumonia and tuberculosis affected 33% of personnel, and 14% were diagnosed with sexually transmitted infections. Diseases reflecting hazardous environmental conditions were relatively common e.g., for dysentery/gastroenteritis in 12% and scabies in 5% of personnel. Diagnoses suggestive of post-traumatic stress disorder (PTSD) were present in 10% and chemical warfare injuries in 6%. CONCLUSIONS: The overall morbidity burden of this military force in WWI was very high, and much higher than the previous official estimates.
Asunto(s)
Personal Militar , Trastornos por Estrés Postraumático , Veteranos , Humanos , Primera Guerra Mundial , Nueva Zelanda/epidemiología , Trastornos por Estrés Postraumático/diagnósticoRESUMEN
In this article we review the COVID-19 pandemic experience in Aotearoa New Zealand and consider the optimal ongoing response strategy. We note that this pandemic virus looks likely to result in future waves of infection that diminish in size over time, depending on such factors as viral evolution and population immunity. However, the burden of disease remains high with thousands of infections, hundreds of hospitalisations and tens of deaths each week, and an unknown burden of long-term illness (long COVID). Alongside this there is a considerable burden from other important respiratory illnesses, including influenza and RSV, that needs more attention. Given this impact and the associated health inequities, particularly for Maori and Pacific Peoples, we consider that an ongoing respiratory disease mitigation strategy is appropriate for New Zealand. As such, the previously described "vaccines plus" approach (involving vaccination and public health and social measures), should now be integrated with the surveillance and control of other important respiratory infections. Now is also a time for New Zealand to build on the lessons from the COVID-19 pandemic to enhance preparedness nationally and internationally. New Zealand's experience suggests elimination (or ideally exclusion) should be the default first choice for future pandemics of sufficient severity.
Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Nueva Zelanda/epidemiología , Síndrome Post Agudo de COVID-19 , Pandemias/prevención & control , Pueblo MaoríRESUMEN
AIM: We aimed to estimate the current dietary energy content of food exports for Aotearoa New Zealand and food security during "nuclear winter" scenarios following a nuclear war. METHODS: From published sources we estimated dietary energy available from the major domains of food exports, with adjustments for wastage. The impacts on food production in New Zealand during three nuclear winter scenarios were based on those published in Nature Food in 2022 and from an earlier New Zealand Planning Council study. RESULTS: Current major food exports are equivalent to 3.9 times current dietary energy intakes for all New Zealand citizens i.e., 34,100 kJ (8150 kcal) per person per day. Exported dairy products were estimated to be able to provide 338% of this energy intake, followed by exports of meat (34%), fruit (8.6%), alcohol (4.8%), marine products (4.6%) and vegetables (2.7%). During the various nuclear winter scenarios considered (minimal to severe), food production available from diverted exported foods was estimated to still be 3.6 to 1.5 times current daily energy intakes. Nevertheless, the agriculture sector could be at risk of various levels of collapse from lack of imports (e.g., diesel, fertiliser, pesticides, seeds, and machinery parts) and from socio-economic collapse, including if the financial system collapsed. CONCLUSIONS: This analysis suggests that this country could theoretically have excess food production capacity, even after a severe nuclear winter scenario. But this benefit could be very short-term if the agricultural system was not made more resilient to potential lack of international trade and socio-economic collapse in a post-catastrophe setting.
Asunto(s)
Comercio , Internacionalidad , Humanos , Nueva Zelanda , Dieta , Frutas , Agricultura , Seguridad Alimentaria , VerdurasRESUMEN
This study aimed to estimate the optimal mix of frost resistant crops and land area needed to provide basic nutrition during various nuclear winter scenarios for New Zealand (NZ), a temperate island nation. It used linear programming to minimize land area required for cropping while producing enough food to achieve dietary energy and protein requirements for the whole population. The potential agricultural impacts of three nuclear winter scenarios on NZ, were sourced from the literature. The optimized combinations of frost resistant crops that were found to feed the entire population were, in descending order: wheat and carrots; sugar beet; oats; onions and carrots; cabbage and barley; canola and cabbage; linseed and parsnip; rye and lupins; swede and field beans; and cauliflower. But in terms of current production levels of these frost resistant crops in NZ, there would be a 26% shortfall for the "war without a nuclear winter" scenario and a 71% shortfall for the severe nuclear winter scenario (150 Tg of soot in the stratosphere with a 61% decline in crop yields). In conclusion, at current production levels, frost resistant food crops could not feed all NZ citizens following a nuclear war. There is a need for the NZ Government to conduct a detailed pre-war analysis on how these shortfalls are best addressed. For example, by: increased pre-war production of these crops and/or post-war scalability; growing enough frost sensitive crops (i.e., in greenhouses or the warmest parts of the country); and/or ensuring continuing production of food derived from livestock fed on frost resistant grasses.
Asunto(s)
Agricultura , Producción de Cultivos , Estaciones del Año , Productos Agrícolas , Poaceae , Abastecimiento de AlimentosRESUMEN
Two key shortcomings of national risk assessments (NRAs) are: (1) lack of justification and transparency around important foundational assumptions of the process, (2) omission of almost all the largest scale risks. Using a demonstration set of risks, we illustrate how NRA process assumptions around time horizon, discount rate, scenario choice, and decision rule impact on risk characterization and therefore any subsequent ranking. We then identify a neglected set of large-scale risks that are seldom included in NRAs, namely global catastrophic risks and existential threats to humanity. Under a highly conservative approach that considers only simple probability and impact metrics, the use of significant discount rates, and harms only to those currently alive at the time, we find these risks have likely salience far greater than their omission from national risk registers might suggest. We highlight the substantial uncertainty inherent in NRAs and argue that this is reason for more engagement with stakeholders and experts. Widespread engagement with an informed public and experts would legitimize key assumptions, encourage critique of knowledge, and ease shortcomings of NRAs. We advocate for a deliberative public tool that can support informed two-way communication between stakeholders and governments. We outline the first component of such a tool for communication and exploration of risks and assumptions. The most important factors for an "all hazards" approach to NRA are ensuring license for key assumptions and that all the salient risks are included before proceeding to ranking of risks and considering resource allocation and value.
RESUMEN
INTRODUCTION: Tobacco companies claim that substantially reducing tobacco retail outlets in Aotearoa New Zealand will increase illicit tobacco trade and crime. However, we know little about whether people who smoke anticipate using illicit tobacco once this measure is implemented. Exploring current illicit tobacco use and expected market development would clarify the likely scale of this potential problem. AIMS AND METHODS: We undertook online in-depth interviews with 24 adults who smoke and explored their experiences of illicit tobacco, perceptions of illicit market growth once legal tobacco became less available, intentions to engage in this market, and potential measures that could curb illicit market development. We interpreted the data using a qualitative descriptive approach. RESULTS: Few participants had purchased illegally imported or stolen tobacco. While most did not know how to access illicit tobacco products, many expected illicit trade and crime would increase, if legal tobacco became difficult to access. While cheaper tobacco appealed to many, most perceived illicit supply routes as unsafe and saw products obtained via these sources as likely to be of poor quality. Few suggested measures to control illicit markets, though a minority called for social reforms to reduce poverty, which they thought fueled illegal practices. CONCLUSIONS: Although illicit trade may appear to threaten new policy initiatives, participants' limited knowledge of these markets and concerns regarding product safety suggest illegal tobacco may pose less of a threat than tobacco companies have claimed. Policy makers should not be deterred from reducing tobacco availability by industry arguments. IMPLICATIONS: Although participants believed illicit trade would increase if the number of tobacco retailers was substantially reduced, few anticipated purchasing illegal tobacco. They viewed supply routes as unsafe and product quality as likely to be low. Industry predictions that illicit tobacco trade will grow if tobacco becomes less available do not reflect how people who smoke expect to engage with these markets and should not deter the introduction of retail reduction measures.
Asunto(s)
Industria del Tabaco , Productos de Tabaco , Adulto , Humanos , Comercio , Nueva Zelanda/epidemiología , Fumar , Productos de Tabaco/legislación & jurisprudencia , Tráfico de DrogasRESUMEN
Island nations may have potential long-term survival value for humanity in global catastrophes such as sun-blocking catastrophes from nuclear winter and large magnitude volcanic eruptions. One way to explore this issue further is to understand the impact on islands after the largest historically observed volcanic eruption: that of Mt Tambora in 1815. For each of the 31 large, populated islands selected, we conducted literature searches for relevant historical and palaeoclimate studies. We also analysed results from a reconstruction (EKF400v2), which uses atmospheric-only general circulation model simulations with assimilated observational and proxy data. From the literature review, there was widespread evidence for weather/climate anomalies in 1815-1817 for these islands (29/29 for those with data). But missing data was an issue for other dimensions such as impaired food production (seen in 8 islands out of only 12 with data). Based on the EKF400v2 reconstruction for temperature anomalies (compared to the relatively "non-volcanic" reference period of 1779 to 1808), the islands had lower temperature anomalies in the 1815-1818 period than latitudinally equivalent continental sites (at 100 km and 1000 km inland). This was statistically significant for the great majority of the comparisons for group analyses by hemisphere, oceans, and temperate/tropical zone. When considering just the islands, all but four showed statistically anomalous temperature reductions in the 1816-1817 period (for most p < 0.00001). In the peak impact year of 1816, the lowest anomalies were seen for islands in the Southern Hemisphere (p < 0.0001), the Indian Ocean (p < 0.0001), and in the tropics and subtropics of the Southern Hemisphere (p = 0.0057). In conclusion, the findings of both the literature review and reconstruction simulations suggest climatic impacts of the Tambora eruption for nearly all these 31 large islands, albeit less than for continental sites. Islands with the smallest temperature anomalies were in the Southern Hemisphere, in particular the Indian Ocean and the tropics and subtropics of the Southern Hemisphere.
RESUMEN
OBJECTIVES: To optimise planning of public health services, the impact of high-cost users needs to be considered. However, most of the existing statistical models for costs do not include many clinical and social variables from administrative data that are associated with elevated health care resource use, and are increasingly available. This study aimed to use machine learning approaches and big data to predict high-cost users among people with cardiovascular disease (CVD). METHODS: We used nationally representative linked datasets in New Zealand to predict CVD prevalent cases with the most expensive cost belonging to the top quintiles by cost. We compared the performance of four popular machine learning models (L1-regularised logistic regression, classification trees, k-nearest neighbourhood (KNN) and random forest) with the traditional regression models. RESULTS: The machine learning models had far better accuracy in predicting high health-cost users compared with the logistic models. The harmony score F1 (combining sensitivity and positive predictive value) of the machine learning models ranged from 30.6% to 41.2% (compared with 8.6-9.1% for the logistic models). Previous health costs, income, age, chronic health conditions, deprivation, and receiving a social security benefit were among the most important predictors of the CVD high-cost users. CONCLUSIONS: This study provides additional evidence that machine learning can be used as a tool together with big data in health economics for identification of new risk factors and prediction of high-cost users with CVD. As such, machine learning may potentially assist with health services planning and preventive measures to improve population health while potentially saving healthcare costs.
RESUMEN
BACKGROUND: Recent studies linking low levels of nitrate in drinking water to colorectal cancer have raised public concerns over nitrate contamination. The aim of this study was to analyze the media discourse on the potential human health hazard of nitrates in drinking water in a high-income country with a large livestock industry: New Zealand (NZ). METHODS: Searches of media sources ("major newspapers") held by the Factiva database for the NZ setting in the five-year period 17 December 2016 to 20 December 2021. RESULTS: The largest number of media items was observed for 2017 (n = 108), the year of a NZ general election, with a notable decrease in 2020 (n = 20) that was likely due to the Covid-19 pandemic, which dominated health media. However, the percentage of these media items with a health focus steadily increased over time, from 11.1% of all articles in 2017 to 51.2% in 2021. The most commonly mentioned health hazard was colorectal cancer, followed by methemoglobinemia. The temporal pattern of media items suggests that the release of scientific studies and scholarly blogs was associated with the publication of subsequent media items. Major stakeholders involved in the discourse included representatives of local and central government, environmental and recreational interest groups, researchers, local residents, agricultural interest groups, and health organizations. Maori (Indigenous New Zealanders) values or perspectives were rarely mentioned. CONCLUSIONS: Analysis of major newspapers for a five-year period indicated that a wide range of expert comment and opinions were made available to the public and policy makers on the issue of nitrates in water. While many different stakeholder views were captured in the media discourse, there is scope for the media to better report the views of Maori on this topic. There is also a need for articles detailing the health issues to also refer to the environmental, recreational, and cultural aspects of protecting water quality to ensure that the public, policy makers, and regulators are aware of co-benefits.
Asunto(s)
COVID-19 , Neoplasias Colorrectales , Agua Potable , Humanos , Nitratos/efectos adversos , Nitratos/análisis , Agua Potable/análisis , PandemiasRESUMEN
BACKGROUND: Neutrophils have been shown to contribute to the pathophysiology of hidradenitis suppurativa (HS), a chronic, painful and debilitating inflammatory skin disease, yet their exact role remains to be fully defined. Granulocyte colony-stimulating factor (G-CSF), a major regulator of neutrophil development and survival, can be blocked by the novel, fully human anti-G-CSF receptor (G-CSFR) monoclonal antibody CSL324. OBJECTIVES: We investigated the activation and migration of neutrophils in HS and the impact of blocking G-CSFR with CSL324. METHODS: Biopsy and peripheral blood samples were taken from participants of two studies: 2018.206, a noninterventional research study of systemic and dermal neutrophils and inflammatory markers in patients with neutrophilic skin diseases, and CSL324_1001 (ACTRN12616000846426), a single-dose ascending and repeated dose, randomized, double-blind, placebo-controlled study to assess the safety, pharmacokinetics and pharmacodynamics of CSL324 in healthy adult subjects. Ex vivo experiments were performed, including neutrophil enumeration and immunophenotyping, migration, receptor occupancy and transcriptome analysis. RESULTS: The number of cells positive for the neutrophil markers myeloperoxidase (MPO) and neutrophil elastase (NE) was significantly higher in HS lesions compared with biopsies from healthy donors (HDs) (P < 0.0001 and P = 0.0223, respectively). In peripheral blood samples, mean neutrophil counts were significantly higher in patients with HS than in HDs (2.98 vs. 1.60 × 109 L-1, respectively; P = 8.8 × 10-4). Neutrophil migration pathways in peripheral blood were increased in patients with HS and their neutrophils demonstrated an increased migration phenotype, with higher mean CXCR1 on the surface of neutrophils in patients with HS (24453.20 vs. 20798.47 for HD; P = 0.03). G-CSF was a key driver of the transcriptomic changes in the peripheral blood of patients with HS and was elevated in serum from patients with HS compared with HDs (mean 6.61 vs. 3.84 pg mL-1, respectively; P = 0.013). Administration of CSL324 inhibited G-CSF-induced transcriptional changes in HDs, similar to those observed in the HS cohort, as highlighted by expression changes in genes related to neutrophil migratory capacity. CONCLUSIONS: Data suggest that neutrophils contribute to HS pathophysiology and that neutrophils are increased in lesions due to an increase in G-CSF-driven migration. CSL324 counteracted G-CSF-induced transcriptomic changes and blocked neutrophil migration by reducing cell-surface levels of chemokine receptors.
Asunto(s)
Hidradenitis Supurativa , Receptores de Factor Estimulante de Colonias de Granulocito , Adulto , Humanos , Receptores de Factor Estimulante de Colonias de Granulocito/metabolismo , Neutrófilos , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/metabolismo , Receptores del Factor Estimulante de Colonias/metabolismo , Factor Estimulante de Colonias de Granulocitos/farmacologíaRESUMEN
AIMS: We aimed to compare COVID-19 control measures, epidemiological characteristics and economic performance measures in two high-income island nations with small populations, favorable border control options, and relatively good outcomes: Iceland and New Zealand (NZ). METHODS: We examined peer-reviewed journal articles, official websites, reports, media releases and press articles for data on pandemic preparedness and COVID-19 public health responses from 1 January 2020 to 1 June 2022 in Iceland and NZ. We calculated epidemiological characteristics of the COVID-19 pandemic, as well as measures of economic performance. RESULTS: Both nations had the lowest excess mortality in the OECD from the start of the pandemic up to June 2022. Iceland pursued a mitigation strategy, never used lockdowns or officially closed its border to foreign nationals, and instead relied on extensive testing and contact tracing early in the pandemic. Meanwhile, NZ pursued an elimination strategy, used a strict national lockdown to stop transmission, and closed its international border to everyone except citizens and permanent residents going through quarantine and testing. Iceland experienced a larger decrease in gross domestic product in 2020 (relative to 2019) than NZ (-8·27% vs. -1·22%, respectively). In late 2021, NZ announced a shift to a suppression strategy and in 2022 began to reopen its border in stages, while Iceland ended all public restrictions on 25 February 2022. CONCLUSIONS: Many of Iceland's and NZ's pandemic control measures appeared successful and features of the responses in both countries could potentially be adopted by other jurisdictions to address future disease outbreaks and pandemic threats.
Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , Pandemias/prevención & control , Islandia/epidemiología , Control de Enfermedades Transmisibles , Nueva Zelanda/epidemiologíaRESUMEN
BACKGROUND: The Aotearoa/New Zealand Government is aiming to end the tobacco epidemic and markedly reduce Maori:non-Maori health inequalities by legislating: (1) denicotinisation of retail tobacco, (2) 95% reduction in retail outlets and (c) a tobacco free-generation whereby people born after 2005 are unable to legally purchase tobacco. This paper estimates future smoking prevalence, mortality inequality and health-adjusted life year (HALY) impacts of these strategies. METHODS: We used a Markov model to estimate future yearly smoking and vaping prevalence, linked to a proportional multistate life table model to estimate future mortality and HALYs. RESULTS: The combined package of strategies (plus media promotion) reduced adult smoking prevalence from 31.8% in 2022 to 7.3% in 2025 for Maori, and 11.8% to 2.7% for non-Maori. The 5% smoking prevalence target was forecast to be achieved in 2026 and 2027 for Maori males and females, respectively.The HALY gains for the combined package over the population's remaining lifespan were estimated to be 594 000 (95% uncertainty interval (UI): 443 000 to 738 000; 3% discount rate). Denicotinisation alone achieved 97% of these HALYs, the retail strategy 19% and tobacco-free generation 12%.By 2040, the combined package was forcat to reduce the gap in Maori:non-Maori all-cause mortality rates for people 45+ years old by 22.9% (95% UI: 19.9% to 26.2%) for females and 9.6% (8.4% to 11.0%) for males. CONCLUSION: A tobacco endgame strategy, especially denicotinisation, could deliver large health benefits and dramatically reduce health inequities between Maori and non-Maori in Aotearoa/New Zealand.