Nourishing the Infant Gut Microbiome to Support Immune Health: Protocol of SUN (Seeding Through Feeding) Randomized Controlled Trial.

BACKGROUND: The introduction of complementary foods during the first year of life influences the diversity of the gut microbiome. How this diversity affects immune development and health is unclear. OBJECTIVE: This study evaluates the effect of consuming kumara or kumara with added banana powder (resistant starch) compared to a reference control at 4 months post randomization on the prevalence of respiratory tract infections and the development of the gut microbiome. METHODS: This study is a double-blind, randomized controlled trial of mothers and their 6-month-old infants (up to n=300) who have not yet started solids. Infants are randomized into one of 3 groups: control arm (C), standard kumara intervention (K), and a kumara intervention with added banana powder product (K+) to be consumed daily for 4 months until the infant is approximately 10 months old. Infants are matched for sex using stratified randomization. Data are collected at baseline (prior to commencing solid food) and at 2 and 4 months after commencing solid food (at around 8 and 10 months of age). Data and samples collected at each timepoint include weight and length, intervention adherence (months 2 and 4), illness and medication history, dietary intake (months 2 and 4), sleep (diary and actigraphy), maternal dietary intake, breast milk, feces (baseline and 4 months), and blood samples (baseline and 4 months). RESULTS: The trial was approved by the Health and Disability Ethics Committee of the Ministry of Health, New Zealand (reference 20/NTA/9). Recruitment and data collection did not commence until January 2022 due to the COVID-19 pandemic. Data collection and analyses are expected to conclude in January 2024 and early 2025, respectively. Results are to be published in 2024 and 2025. CONCLUSIONS: The results of this study will help us understand how the introduction of a specific prebiotic complementary food affects the microbiota and relative abundances of the microbial species, the modulation of immune development, and infant health. It will contribute to the expanding body of research that aims to deepen our understanding of the connections between nutrition, gut microbiota, and early-life postnatal health. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620000026921; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378654. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56772.

Diabetes treatment satisfaction among a multi-ethnic Aotearoa New Zealand population with uncontrolled type 2 diabetes mellitus.

AIMS: To assess whether diabetes treatment satisfaction differs by ethnicity among participants with insufficient glycaemic control of type 2 diabetes mellitus in a clinical trial involving additional oral diabetes medications. Patient satisfaction is used as an indicator of healthcare quality. However, data on patients' diabetes treatment satisfaction in the context of insufficient glycaemic control is limited. METHODS: Individuals with type 2 diabetes and an HbA1c of 58-110mmol/mol (7.5-12.5%) were recruited across Aotearoa New Zealand to participate in an 8-month randomised crossover study of vildagliptin and pioglitazone as add-on therapy to metformin and/or sulfonylurea. Participants completed the Diabetes Treatment Satisfaction Questionnaire (DTSQ) at baseline pre-randomisation. Treatment satisfaction scores were compared between ethnic groups and other characteristics using the analysis of variance and linear regression. Perceived hyper- and hypoglycaemia were summarised separately. RESULTS: Between February 2019 and March 2020, 346 participants (41% women, 32% Pacific peoples, 23% Maori, 26% European) completed the DTSQ. Mean (SD) age was 57.5 (10.9) years, diabetes duration was 9 (6.3) years and HbA1c was 75 (12)mmol/mol (9.0[3.2]%). At study entry, 40% were receiving monotherapy for diabetes. Treatment satisfaction was rated highly, with a score of 29(6) (interquartile range 25-33). Pacific peoples and older people reported greater treatment satisfaction than other groups (p<0.001). CONCLUSIONS: Diabetes treatment satisfaction was high, particularly among Pacific peoples, despite suboptimal glycaemic control and insufficient glucose-lowering therapy.

Perception is reality: qualitative insights into how consumers perceive alcohol warning labels.

AIMS: This study explores perspectives of on-pack alcohol warning labels, and how they might influence alcohol purchase and/or consumption behavior to inform culturally appropriate label design for effective behavior change. METHODS: New Zealand participants ≥18 years, who reported having purchased and consumed alcoholic beverages in the last month were recruited via a market research panel and grouped into 10 focus groups (n = 53) by ethnicity (general population, Maori, and Pacific peoples), age group, and level of alcohol consumption. Participants were shown six potential alcohol health warning labels, with design informed by relevant literature, label framework, and stakeholder feedback. Interviews were transcribed and analyzed via qualitative (directed) content analysis. RESULTS: Effective alcohol labels should be prominent, featuring large red and/or black text with a red border, combining text with visuals, and words like "WARNING" in capitals. Labels should contrast with bottle color, be easily understood, and avoid excessive text and confusing imagery. Participants preferred specific health outcomes, such as heart disease and cancer, increasing message urgency and relevance. Anticipated behavior change included reduced drinking and increased awareness of harms, but some may attempt to mitigate warnings by covering or removing labels. Contextual factors, including consistent design and targeted labels for different beverages and populations, are crucial. There was a strong emphasis on collective health impacts, particularly among Maori and Pacific participants. CONCLUSIONS: Our findings indicate that implementing alcohol warning labels, combined with comprehensive strategies like retail and social marketing campaigns, could effectively inform and influence the behavior of New Zealand's varied drinkers.

Awareness, support, and opinions of healthy food and drink policies: a survey of staff and visitors in New Zealand healthcare organisations.

BACKGROUND: In 2016, a voluntary National Healthy Food and Drink Policy (hereafter, "the Policy") was released to encourage public hospitals in New Zealand to provide food and drink options in line with national dietary guidelines. Five years later, eight (of 20) organisations had adopted it, with several preferring to retain or update their own institutional-level version. This study assessed staff and visitors' awareness and support for and against the Policy, and collected feedback on perceived food environment changes since implementation of the Policy. METHODS: Cross-sectional electronic and paper-based survey conducted from June 2021 to August 2022. Descriptive statistics were used to present quantitative findings. Free-text responses were analysed following a general inductive approach. Qualitative and quantitative findings were compared by level of implementation of the Policy, and by ethnicity and financial security of participants. RESULTS: Data were collected from 2,526 staff and 261 visitors in 19 healthcare organisations. 80% of staff and 56% of visitors were aware of the Policy. Both staff and visitors generally supported the Policy, irrespective of whether they were aware of it or not, with most agreeing that "Hospitals should be good role models." Among staff who opposed the Policy, the most common reason for doing so was freedom of choice. The Policy had a greater impact, positive and negative, on Maori and Pacific staff, due to more frequent purchasing onsite. Most staff noticed differences in the food and drinks available since Policy implementation. There was positive feedback about the variety of options available in some hospitals, but overall 40% of free text comments mentioned limited choice. 74% of staff reported that food and drinks were more expensive. Low-income staff/visitors and shift workers were particularly impacted by reduced choice and higher prices for healthy options. CONCLUSIONS: The Policy led to notable changes in the healthiness of foods and drinks available in NZ hospitals but this was accompanied by a perception of reduced value and choice. While generally well supported, the findings indicate opportunities to improve implementation of food and drink policies (e.g. providing more healthy food choices, better engagement with staff, and keeping prices of healthy options low) and confirm that the Policy could be expanded to other public workplaces.

Early hypophosphataemia and refeeding syndrome in extremely low birthweight babies and outcomes to 2 years of age: secondary cohort analysis from the ProVIDe trial.

OBJECTIVE: To investigate in extremely low birthweight (ELBW; <1000 g) babies the associations between refeeding syndrome (serum phosphate <1.4 mmol·L-1 and serum total calcium>2.8 mmol·L-1) and hypophosphataemia in the first week and death or neurodisability at 2 years' corrected age (CA). DESIGN: Secondary cohort analysis of the ProVIDe trial participants with serum biochemistry within 7 days of birth. At 2 years' CA, neurodisability was assessed by Bayley Scales of Infant Development Edition III and neurological examination. Associations between neurodisability and other variables were analysed using t-tests and logistic regression adjusted for sex and smallness-for-gestational age. SETTING: Six tertiary neonatal intensive care units (NICUs) in New Zealand. PARTICIPANTS: 352 ELBW babies born between 29 April 2014 and 30 October 2018. MAIN OUTCOME MEASURE: Death or neurodisability at 2 years' CA. RESULTS: Fifty-nine babies died, two after discharge from the NICU. Of the 336 babies who survived to 2 years' CA, 277 had neurodevelopmental assessment and 107 (39%) had a neurodisability. Death or neurodisability was more likely in babies who had refeeding syndrome (aOR 1.96 (95% CI 1.09 to 3.53), p=0.02) and in babies who had hypophosphataemia (aOR 1.74 (95% CI 1.09 to 2.79), p=0.02). Hypophosphataemia was associated with increased risk of death (aOR 2.07 (95% CI 1.09 to 3.95), p=0.03)) and severe hypophosphataemia (<0.9 mmol·L-1) with increased risk of death (aOR 2.67 (95% CI 1.41 to 5.00), p=0.002) and neurodisability (aOR 2.31 (95% CI 1.22 to 4.35), p=0.01). CONCLUSIONS: In ELBW babies, refeeding syndrome and hypophosphataemia in the first week are associated with death or neurodisability. Until optimal phosphate requirements are determined through further research, monitoring for hypophosphataemia and mitigation strategies are indicated. TRIAL REGISTRATION NUMBER: ACTRN12612001084875.

Long-term cost-effectiveness analysis of rugby fans in training-New Zealand: a body weight reduction programme for males.

OBJECTIVES: We sought to extrapolate the long-term costs and clinical impacts attributed to the rugby fans in training-New Zealand (RUFIT-NZ) trial in Aotearoa, New Zealand. DESIGN: A modelled cost-effectiveness analysis using efficacy data from RUFIT-NZ was conducted from the Aotearoa New Zealand healthcare perspective. SETTING: A Markov cohort model was constructed with a lifetime time horizon. The model simulated events of myocardial infarction (MI), stroke and type 2 diabetes mellitus (T2DM) occurring among a hypothetical cohort of 10 000 individuals receiving either the RUFIT-NZ intervention or no intervention. Efficacy data were based on the RUFIT-NZ trial, and the latest Global Burden of Disease study was used to extrapolate the impact of body weight reduction on clinical outcomes of T2DM, MI or stroke. Cost and utility data were drawn from the RUFIT-NZ trial and published sources. PRIMARY OUTCOME MEASURES: The incremental cost-effectiveness ratio (ICER). RESULTS: Over a lifetime time horizon, participants in the RUFIT-NZ intervention gained 0.02 (discounted) quality-adjusted life years (QALYs) at an additional cost of NZ$863, relative to no intervention. The estimated ICER was NZ$49 515 per QALY gained (discounted), which is above the arbitrary willingness-to-pay threshold of NZ$45 000 per QALY. Sensitivity analyses supported the robustness of these findings. CONCLUSIONS: RUFIT-NZ was associated with a reduction in cardiovascular and endocrine events for overweight and obese males. However, based on conservative assumptions, RUFIT-NZ was unlikely to be cost-effective from a healthcare system perspective. TRIAL REGISTRATION NUMBER: ACTRN12619000069156.

Methods and clinical biomarker discovery for targeted proteomics using Olink technology.

PURPOSE: This paper is to offer insights for designing research utilizing Olink technology to identify biomarkers and potential therapeutic targets for disease treatment. EXPERIMENTAL DESIGN: We discusses the application of Olink technology in oncology, cardiovascular, respiratory and immune-related diseases, and Outlines the advantages and limitations of Olink technology. RESULTS: Olink technology simplifies the search for therapeutic targets, advances proteomics research, reveals the pathogenesis of diseases, and ultimately helps patients develop precision treatments. CONCLUSIONS: Although proteomics technology has been rapidly developed in recent years, each method has its own disadvantages, so in the future research, more methods should be selected for combined application to verify each other.

Investigating the relationship between prenatal alcohol exposure and children's behavioural and emotional development: analysis of the Growing Up in New Zealand study.

AIMS: To examine the relationship between prenatal alcohol exposure (PAE) and children's behavioural and emotional development in a large generalizable sample of women and their children in Aotearoa New Zealand. METHODS: Using data from the Growing Up in New Zealand longitudinal cohort, we investigated the relationship between maternal PAE and behavioural and emotional development in 8-year-old children. We explored secondary outcomes including measures of language, executive function, academic achievement, and adaptive behaviour. RESULTS: We found no significant differences in the measures of behavioural and emotional development in children 8 years old based on alcohol consumption. No significant differences in behavioural and emotional development were found based on amount of PAE and when PAE occurred, despite controlling for a range of potential confounding factors, such as neighbourhood deprivation and maternal health measures. PAE was associated with significantly higher scores for parent-rated oral language indicating better oral language. In Maori mothers, PAE was significantly associated with an increased risk of higher scores on two of the Strengths and Difficulties Questionnaire subscales. CONCLUSIONS: We did not find an association between PAE and behavioural and emotional development in children aged 8 years. PAE and behavioural and emotional development are difficult to measure accurately, and the moderating variables between them are complex. Future analyses will require larger cohorts of mothers and their children using precise measures of PAE and outcomes to enable more precise estimates of association.

Nutritional Support for Moderate-to-Late-Preterm Infants - A Randomized Trial.

BACKGROUND: Most moderate-to-late-preterm infants need nutritional support until they are feeding exclusively on their mother's breast milk. Evidence to guide nutrition strategies for these infants is lacking. METHODS: We conducted a multicenter, factorial, randomized trial involving infants born at 32 weeks 0 days' to 35 weeks 6 days' gestation who had intravenous access and whose mothers intended to breast-feed. Each infant was assigned to three interventions or their comparators: intravenous amino acid solution (parenteral nutrition) or dextrose solution until full feeding with milk was established; milk supplement given when maternal milk was insufficient or mother's breast milk exclusively with no supplementation; and taste and smell exposure before gastric-tube feeding or no taste and smell exposure. The primary outcome for the parenteral nutrition and the milk supplement interventions was the body-fat percentage at 4 months of corrected gestational age, and the primary outcome for the taste and smell intervention was the time to full enteral feeding (150 ml per kilogram of body weight per day or exclusive breast-feeding). RESULTS: A total of 532 infants (291 boys [55%]) were included in the trial. The mean (±SD) body-fat percentage at 4 months was similar among the infants who received parenteral nutrition and those who received dextrose solution (26.0±5.4% vs. 26.2±5.2%; adjusted mean difference, -0.20; 95% confidence interval [CI], -1.32 to 0.92; P = 0.72) and among the infants who received milk supplement and those who received mother's breast milk exclusively (26.3±5.3% vs. 25.8±5.4%; adjusted mean difference, 0.65; 95% CI, -0.45 to 1.74; P = 0.25). The time to full enteral feeding was similar among the infants who were exposed to taste and smell and those who were not (5.8±1.5 vs. 5.7±1.9 days; P = 0.59). Secondary outcomes were similar across interventions. Serious adverse events occurred in one infant. CONCLUSIONS: This trial of routine nutrition interventions to support moderate-to-late-preterm infants until full nutrition with mother's breast milk was possible did not show any effects on the time to full enteral feeding or on body composition at 4 months of corrected gestational age. (Funded by the Health Research Council of New Zealand and others; DIAMOND Australian New Zealand Clinical Trials Registry number, ACTRN12616001199404.).

Examining the impact of COVID-19 on Maori:non-Maori health inequities in Aotearoa, New Zealand: an observational study protocol.

INTRODUCTION: The COVID-19 pandemic has had both direct and indirect impacts on the health of populations worldwide. While racial/ethnic health inequities in COVID-19 infection are now well known (and ongoing), knowledge about the impact of COVID-19 pandemic management on non-COVID-19-related outcomes for Indigenous peoples is less well understood. This article presents the study protocol for the Health Research Council of New Zealand funded project 'Ma te Mohio ka Marama: Impact of COVID-19 on Maori:non-Maori inequities'. The study aims to explore changes in access to healthcare, quality of healthcare and health outcomes for Maori, the Indigenous peoples of Aotearoa New Zealand (NZ) and non-Maori during the COVID-19 outbreak period across NZ. METHODS AND ANALYSIS: This observational study is framed within a Kaupapa Maori research positioning that includes Kaupapa Maori epidemiology. National datasets will be used to report on access to healthcare, quality of healthcare and health outcomes between Maori and non-Maori during the COVID-19 pandemic in NZ. Study periods are defined as (a) prepandemic period (2015-2019), (b) first pandemic year without COVID-19 vaccines (2020) and (c) pandemic period with COVID-19 vaccines (2021 onwards). Regional and national differences between Maori and non-Maori will be explored in two phases focused on identified health priority areas for NZ including (1) mortality, cancer, long-term conditions, first 1000 days, mental health and (2) rheumatic fever. ETHICS AND DISSEMINATION: This study has ethical approval from the Auckland Health Research Ethics Committee (AHREC AH26253). An advisory group will work with the project team to disseminate the findings of this project via project-specific meetings, peer-reviewed publications and a project-specific website. The overall intention of the project is to highlight areas requiring health policy and practice interventions to address Indigenous inequities in health resulting from COVID-19 pandemic management (both historical and in the future).

Serum Olink Proteomics-Based Identification of Protein Biomarkers Associated with the Immune Response in Ischemic Stroke.

The immune response is considered essential for pathology of ischemic stroke (IS), but it remains unclear which immune response-related proteins exhibit altered expression in IS patients. Here, we used Olink proteomics to examine the expression levels of 92 immune response-related proteins in the sera of IS patients (n = 88) and controls (n = 88), and we found that 59 of these proteins were differentially expressed. Feature variables were screened from the differentially expressed proteins by the least absolute shrinkage and selection operator (LASSO) and the random forest and by determining whether their proteins had an area under the curve (AUC) greater than 0.8. Ultimately, we identified six potential protein biomarkers of IS, namely, MASP1, STC1, HCLS1, CLEC4D, PTH1R, and PIK3AP1, and established a logistic regression model that used these proteins to diagnose IS. The AUCs of the models in the internal validation and the test set were 0.962 (95% confidence interval (CI): 0.895-1.000) and 0.954 (95% CI: 0.884-1.000), respectively, and the same protein detection method was performed in an external independent validation set (AUC: 0.857 (95% CI: 0.801-0.913)). These proteins may play a role in immune regulation via the C-type lectin receptor signaling pathway, the PI3K-AKT signaling pathway, and the B-cell receptor signaling pathway.

Plasma lipidomic profiling reveals six candidate biomarkers for the prediction of incident stroke in patients with hypertension.

INTRODUCTION: The burden of stroke in patients with hypertension is very high, and its prediction is critical. OBJECTIVES: We aimed to use plasma lipidomics profiling to identify lipid biomarkers for predicting incident stroke in patients with hypertension. METHODS: This was a nested case-control study. Baseline plasma samples were collected from 30 hypertensive patients with newly developed stroke, 30 matched patients with hypertension, 30 matched patients at high risk of stroke, and 30 matched healthy controls. Lipidomics analysis was performed by ultrahigh-performance liquid chromatography-tandem mass spectrometry, and differential lipid metabolites were screened using multivariate and univariate statistical methods. Machine learning methods (least absolute shrinkage and selection operator, random forest) were used to identify candidate biomarkers for predicting stroke in patients with hypertension. RESULTS: Co-expression network analysis revealed that the key molecular alterations of the lipid network in stroke implicate glycerophospholipid metabolism and choline metabolism. Six lipid metabolites were identified as candidate biomarkers by multivariate statistical and machine learning methods, namely phosphatidyl choline(40:3p)(rep), cholesteryl ester(20:5), monoglyceride(29:5), triglyceride(18:0p/18:1/18:1), triglyceride(18:1/18:2/21:0) and coenzyme(q9). The combination of these six lipid biomarkers exhibited good diagnostic and predictive ability, as it could indicate a risk of stroke at an early stage in patients with hypertension (area under the curve = 0.870; 95% confidence interval: 0.783-0.957). CONCLUSIONS: We determined lipidomic signatures associated with future stroke development and identified new lipid biomarkers for predicting stroke in patients with hypertension. The biomarkers have translational potential and thus may serve as blood-based biomarkers for predicting hypertensive stroke.

Associations between neonatal nutrition and visual outcomes in 7-year-old children born very preterm.

PURPOSE: There is uncertainty about the effect of increased neonatal protein intake on neurodevelopmental outcomes following preterm birth. The aim of this study was to assess the effect of a change in neonatal nutrition protocol at a major tertiary neonatal intensive care unit intended to increase protein intake on ophthalmic and visual development in school-age children born very preterm. METHODS: The study cohort comprised children (n = 128) with birthweight <1500 g or gestational age < 30 weeks born at Auckland City Hospital before (OldPro group, n = 55) and after (NewPro group, n = 73) a reformulation of parenteral nutrition that resulted in increased total protein intake during the first postnatal week and decreased carbohydrate, total parenteral fluid and sodium intake. Clinical and psychophysical vision assessments were completed at 7 years' corrected age, including visual acuity, global motion perception (a measure of dorsal stream function), stereoacuity, ocular motility and ocular health. Composite measures of favourable overall visual, binocular and functional visual outcomes along with individual vision measures were compared between the groups using logistic and linear regression models. RESULTS: Favourable overall visual outcome did not differ between the two groups. However, global motion perception was better in the NewPro group (p = 0.04), whereas the OldPro group were more likely to have favourable binocular visual outcomes (60% vs. 36%, p = 0.02) and passing stereoacuity (p = 0.02). CONCLUSIONS: These results indicate subtle but complex associations between early neonatal nutrition after very preterm birth and visual development at school age.

New Zealand household purchases of sugar-sweetened, artificially sweetened, and unsweetened beverages: 2015-2019.

OBJECTIVE: To assess annual household purchases of sugar-sweetened beverages (SSBs), artificially sweetened beverages (AFSBs), and unsweetened beverages (USBs) by household composition and income, and over time. DESIGN: Observational cohort study using beverage purchasing data linked to a supermarket database. ANOVA was used to compare total household purchase volumes (L) and the contribution of beverages purchased by category, household composition (size), household income (four categories from New Zealand (NZ) < $30 000 to > $90 000), and over time (trend from 2015 to 2019). SETTING: Aotearoa NZ. PARTICIPANTS: ∼1800 households in the NielsenIQ Homescan® market research panel. RESULTS: In 2019, the mean (sd) annual household purchase volume and relative contribution to total beverage volume of SSBs were 72·3 (93·0) L and 33 %, respectively. Corresponding values for AFSBs were 32·5 (79·3) L (15 %), and USBs were 112·5 (100·9) L (52 %). Larger households purchased more of all beverage types except AFSBs. Total purchases were similar by income, but households earning < $NZ 30 000 purchased fewer AFSBs and USBs (but not SSBs) than households earning > $NZ 90 000. Total and USB purchases were unchanged over time, but SSBs dropped by 5·9 L (P-trend = 0·04), and AFSBs increased by 5·3 L (P-trend = 0·00). CONCLUSIONS: USBs contributed the most to household beverage purchases. Total purchases were higher for larger households and similar by income, including for SSBs. The reduction over time was too small for health benefits. Findings support policies and interventions to reduce SSB consumption and highlight the importance of focusing on equitable outcomes.

Investigation and treatment after non-ST segment elevation acute coronary syndrome for patients presenting to rural or urban hospitals in Aotearoa New Zealand: ANZACS-QI 75.

AIMS: Compare the care patients with non-ST segment elevation acute coronary syndrome (NSTEACS) received in Aotearoa New Zealand depending on the rural-urban category of the hospital they are first admitted to. METHODS: Patients with NSTEACS investigated with invasive coronary angiogram between 1 January 2014 and 31 December 2019 were included. There were three hospital categories (routine access to percutaneous coronary intervention [urban interventional], other urban [urban non-interventional] and rural) and three ethnicity categories (Maori, Pacific and non-Maori/non-Pacific). Clinical performance measures included: angiography ≤3 days, assessment of left ventricular ejection fraction (LVEF) and prescription of secondary prevention medication. RESULTS: Of 26,779 patients, 66.2% presented to urban-interventional, 25.6% to urban non-interventional and 8.2% to rural hospitals. A smaller percentage of patients presenting to urban interventional than urban non-interventional and rural hospitals were Maori (8.1%, 17.0% and 13.0%). Patients presenting to urban interventional hospitals were more likely to receive timely angiography than urban non-interventional or rural hospitals (78.5%, 60.8% and 63.1%). They were also more likely to have a LVEF assessment (78.5%, 65.4% and 66.3%). In contrast, the use of secondary prevention medications at discharge was similar between hospital categories. Maori and Pacific patients presenting to urban interventional hospitals were less likely than non-Maori/non-Pacific to receive timely angiography but more likely to have LVEF assessed. However, LVEF assessment and timely angiography in urban non-interventional and rural hospitals were lower than in urban interventional hospitals for both Maori and non-Maori/non-Pacific. CONCLUSIONS: Patients presenting to urban hospitals without routine interventional access and rural hospitals were less likely to receive LVEF assessment or timely angiography. This disproportionately impacts Maori, who are more likely to live in these hospital catchments.

A simple index to predict healing in venous leg ulcers: a secondary analysis from four randomised controlled trials.

OBJECTIVE: To investigate whether the use of a simple baseline measurement predicts venous leg ulcer healing at 12 and 24 weeks. METHOD: This was a secondary analysis of a cohort of four randomised controlled trials (RCTs) of treatments adjuvant to compression. Self-reported ulcer duration, and measured ulcer length and width, to calculate estimated ulcer area, were used to obtain a Margolis index score. The score created three prognostic strata for likelihood to heal within 24 weeks, and the number of participants healed and time-to-healing were compared. RESULTS: There were a total of 802 participants across the four RCTs-408 (50.9%) in two 12-week trials and 394 (49.1%) in two 24-week trials. The mean age of participants was 63.7±17.6 years, and 372 were female (46.4%). The Margolis index score at baseline was 0 for 320 participants (predicted normal healing); 1 for 334 participants; and 2 for 148 participants (both 1 and 2 predicted slow-to-heal). Overall, 248 (77.5%) of those participants who scored 0 at baseline healed within 24 weeks, compared with 182 (54.5%) of participants who scored 1, and 30 (20.3%) participants who scored 2. The median time-to-healing was 40 (24-62) days, 57 (35-100) days and 86.5 (56-151) days, respectively. The area under the receiver operating characteristic curve was 0.69 and 0.77, respectively, for the 12 and 24 week trials. CONCLUSION: A simple baseline index identifies participants with normal or slow-to-heal wounds and could be used to demonstrate prognostic balance between treatment groups in trials. This approach could also be used in clinical practice to assist with managing expectations and for early identification of patients who may best benefit from adjuvant treatments.

Proteomic advance of ischemic stroke: preclinical, clinical, and intervention.

Ischemic stroke (IS) is the most common type of stroke and is characterized by high rates of mortality and long-term injury. The prediction and early diagnosis of IS are therefore crucial for optimal clinical intervention. Proteomics has provided important techniques for exploring protein markers associated with IS, but there has been no systematic evaluation and review of research that has used these techniques. Here, we review the differential proteins that have been found in cell- and animal- based studies and clinical trials of IS in the past 10 years; determine the key pathological proteins that have been identified in clinical trials; summarize the target proteins affected by interventions aimed at treating IS, with a focus on traditional Chinese medicine treatments. Overall, we clarify findings and problems that have been identified in recent proteomics research on IS and provide suggestions for improvements in this area. We also suggest areas that could be explored for determining the pathogenesis and developing interventions for IS.

Construction of a prognostic model for triple-negative breast cancer based on immune-related genes, and associations between the tumor immune microenvironment and immunological therapy.

BACKGROUND: Triple-negative breast cancer (TNBC) is the subtype of breast cancer with the worst prognosis, and it is highly heterogeneous. There is growing evidence that the tumor immune microenvironment (TIME) plays a crucial role in tumor development, maintenance, and treatment responses. Notably however, the full effects of the TIME on prognosis, TIME characteristics, and immunotherapy responses in TNBC patients have not been fully elucidated. METHODS: Gene Expression Omnibus and The Cancer Genome Atlas data were used to data analysis. Single-cell sequencing and tissue microarray analysis were used to investigate gene expression. The concentrations and distributions of immune cell types were determined and analyzed using the CIBERSORT strategy. Tumor immune dysfunction and exclusion score and the IMvigor210 cohort were used to estimate the sensitivity of TNBC patients with different prognostic statuses to immune checkpoint treatment. RESULTS: Five immune-related genes associated with TNBC prognosis (IL6ST, NR2F1, CKLF, TCF7L2, and HSPA2) was identified and a prognostic evaluation model was constructed based on those genes. The respective areas under the curve of the prognostic nomogram model at 3 and 5 years were 0.791 and 0.859. The group with a lower nomogram score, with a better prognosis survival status and clinical treatment benefit rate. CONCLUSION: A prognostic model for TNBC that was closely related to the immune landscape and therapeutic responses was constructed. This model may help clinicians to make more precise and personalized treatment decisions pertaining to TNBC patients.

Outcomes and access to angiography following non-ST-segment elevation acute coronary syndromes in patients who present to rural or urban hospitals: ANZACS-QI 72.

AIM: This study's aim was to identify differences in invasive angiography performed and health outcomes for patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) presenting to either i) a rural hospital, or an urban hospital ii) with or iii) without routine access to percutaneous intervention (PCI) in New Zealand. METHODS: Patients with NSTEACS between 1 January 2014 and 31 December 2017 were included. Logistic regression was used to model each of the outcome measures: angiography performed within 1 year; 30-day, 1-year and 2-year all-cause mortality; and readmission within 1 year of presentation with either heart failure, a major adverse cardiac event or major bleeding. RESULTS: There were 42,923 patients included. Compared to urban hospitals with access to PCI, the odds of a patient receiving an angiogram were reduced for rural and urban hospitals without routine access to PCI (odds ratio [OR] 0.82 and 0.75) respectively. There was a small increase in the odds of dying at 2 years (OR 1.16), but not 30 days or 1 year for patients presenting to a rural hospital. CONCLUSION: Patients who present to hospitals without PCI are less likely to receive angiography. Reassuringly there is no difference in mortality, except at 2 years, for patients that present to rural hospitals.

Projected Global Trends in Ischemic Stroke Incidence, Deaths and Disability-Adjusted Life Years From 2020 to 2030.

BACKGROUND: We projected global trends in ischemic stroke from 2020 to 2030 according to age, sex, and socio-demographic index (SDI) quintile. METHODS: Estimated annual percentage changes (EAPCs) were used to project trends in the incidence of deaths from and disability-adjusted life years (DALYs) due to ischemic stroke between 2020 and 2030. EAPCs were computed using generalized additive models and data from the Global Burden of Disease study during the 1990 to 2019 period. RESULTS: The global age-standardized incidence rate of ischemic stroke was projected to increase to 89.32 per 100 000 population in 2030 (EAPC=0.89), whereas the associated global age-standardized death and DALY rates were projected to decrease to 18.28 (EAPC, -3.58) and 500.37 per 100 000 (EAPC=-1.75), respectively, in 2030. The projections indicated a higher age-standardized incidence rate of ischemic stroke among women than among men in 2030 (90.70 versus 87.64 per 100 000). The incidence rate of ischemic stroke was projected to increase across all age groups and SDI quintiles between 2020 and 2030. At the national level, the greatest increase in the age-standardized incidence rate of ischemic stroke between 2020 and 2030 was projected to occur in Cyprus (EAPC=4.16), followed by Palestine (EAPC=3.50) and South Africa (EAPC=2.64). Additionally, the projections suggested increases in the age-standardized death and DALY rates due to ischemic stroke for countries in low-SDI quintiles (EAPC=3.68 and EAPC=5.30, respectively). CONCLUSIONS: The projections indicated that the incidence rate of ischemic stroke will increase both sexes, all age groups, and all SDI quintiles and in some countries between 2020 and 2030. Furthermore, countries with a low SDI should be aware of potential increases in the age-standardized death and DALY due to ischemic stroke.