Klebsiella pneumoniae clinical isolates with features of both multidrug-resistance and hypervirulence have unexpectedly low virulence.

Klebsiella pneumoniae has been classified into two types, classical K. pneumoniae (cKP) and hypervirulent K. pneumoniae (hvKP). cKP isolates are highly diverse and important causes of nosocomial infections; they include globally disseminated antibiotic-resistant clones. hvKP isolates are sensitive to most antibiotics but are highly virulent, causing community-acquired infections in healthy individuals. The virulence phenotype of hvKP is associated with pathogenicity loci responsible for siderophore and hypermucoid capsule production. Recently, convergent strains of K. pneumoniae, which possess features of both cKP and hvKP, have emerged and are cause of much concern. Here, we screen the genomes of 2,608 multidrug-resistant K. pneumoniae isolates from the United States and identify 47 convergent isolates. We perform phenotypic and genomic characterization of 12 representative isolates. These 12 convergent isolates contain a variety of antimicrobial resistance plasmids and virulence plasmids. Most convergent isolates contain aerobactin biosynthesis genes and produce more siderophores than cKP isolates but not more capsule. Unexpectedly, only 1 of the 12 tested convergent isolates has a level of virulence consistent with hvKP isolates in a murine pneumonia model. These findings suggest that additional studies should be performed to clarify whether convergent strains are indeed more virulent than cKP in mouse and human infections.

Genome-wide screens reveal shared and strain-specific genes that facilitate enteric colonization by Klebsiella pneumoniae.

Gastrointestinal (GI) colonization by Klebsiella pneumoniae is a risk factor for subsequent infection as well as transmission to other patients. Additionally, colonization is achieved by many strain types that exhibit high diversity in genetic content. Thus, we aimed to study strain-specific requirements for K. pneumoniae GI colonization by applying transposon insertion sequencing to three classical clinical strains: a carbapenem-resistant strain, an extended-spectrum beta-lactamase-producing strain, and a non-epidemic antibiotic-susceptible strain. The transposon insertion libraries were screened in a murine model of GI colonization. At 3 days post-inoculation, 27 genes were required by all three strains for colonization. Isogenic deletion mutants for three genes/operons (acrA, carAB, and tatABCD) confirmed colonization defects in each of the three strains. Additionally, deletion of acrA reduced bile tolerance in vitro, while complementation restored both bile tolerance in vitro and colonization ability in vivo. Transposon insertion sequencing suggested that some genes were more important for the colonization of one strain than the others. For example, deletion of the sucrose porin-encoding gene scrY resulted in a colonization defect in the carbapenemase-producing strain but not in the extended-spectrum beta-lactamase producer or the antibiotic-susceptible strain. These findings demonstrate that classical K. pneumoniae strains use both shared and strain-specific strategies to colonize the mouse GI tract. IMPORTANCE Klebsiella pneumoniae is a common cause of difficult-to-treat infections due to its propensity to express resistance to many antibiotics. For example, carbapenem-resistant K. pneumoniae has been named an urgent threat by the United States Centers for Disease Control and Prevention. Gastrointestinal colonization in patients with K. pneumoniae has been linked to subsequent infection, making it a key process to control in the prevention of multidrug-resistant infections. However, the bacterial factors which contribute to K. pneumoniae colonization are not well understood. Additionally, individual strains exhibit large amounts of genetic diversity, begging the question of whether some colonization factors are strain dependent. This study identifies the enteric colonization factors of three classical strains using transposon mutant screens to define a core colonization program for K. pneumoniae as well as detecting strain-to-strain differences in colonization strategies.

Taxonomic characterization of Pseudomonas hygromyciniae sp. nov., a novel species discovered from a commercially purchased antibiotic.

In an attempt to identify novel bacterial species, microbiologists have examined a wide range of environmental niches. We describe the serendipitous discovery of a novel gram-negative bacterial species from a different type of extreme niche: a purchased vial of antibiotic. The vial of antibiotic hygromycin B was found to be factory contaminated with a bacterial species, which we designate Pseudomonas hygromyciniae sp. nov. The proposed novel species belongs to the P. fluorescens complex and is most closely related to P. brenneri, P. proteolytica, and P. fluorescens. The type strain Pseudomonas hygromyciniae sp. nov. strain SDM007T (SDM007T) harbors a novel 250 kb megaplasmid which confers resistance to hygromycin B and contains numerous other genes predicted to encode replication and conjugation machinery. SDM007T grows in hygromycin concentrations of up to 5 mg/mL but does not use the antibiotic as a carbon or nitrogen source. While unable to grow at 37°C ruling out its ability to infect humans, it grows and survives at temperatures between 4 and 30°C. SDM007T can infect plants, as demonstrated by the lettuce leaf model, and is highly virulent in the Galleria mellonella infection model but is unable to infect mammalian A549 cells. These findings indicate that commercially manufactured antibiotics represent another extreme environment that may support the growth of novel bacterial species. IMPORTANCE Physical and biological stresses in extreme environments may select for bacteria not found in conventional environments providing researchers with the opportunity to not only discover novel species but to uncover new enzymes, biomolecules, and biochemical pathways. This strategy has been successful in harsh niches such as hot springs, deep ocean trenches, and hypersaline brine pools. Bacteria belonging to the Pseudomonas species are often found to survive in these unusual environments, making them relevant to healthcare, food, and manufacturing industries. Their ability to survive in a variety of environments is mainly due to the high genotypic and phenotypic diversity displayed by this genus. In this study, we discovered a novel Pseudomonas sp. from a desiccated environment of a sealed antibiotic bottle that was considered sterile. A close genetic relationship with its phylogenetic neighbors reiterated the need to use not just DNA-based tools but also biochemical characteristics to accurately classify this organism.

Genome-wide screens reveal shared and strain-specific genes that facilitate enteric colonization by Klebsiella pneumoniae.

Gastrointestinal (GI) colonization by Klebsiella pneumoniae is a risk factor for subsequent infection as well as transmission to other patients. Additionally, colonization is achieved by many strain types that exhibit high diversity in genetic content. Thus, we aimed to study strain-specific requirements for K. pneumoniae GI colonization by applying transposon insertion sequencing to three classical clinical strains: a carbapenem-resistant strain, an extended-spectrum beta-lactamase producing strain, and a non-epidemic antibiotic-susceptible strain. The transposon insertion libraries were screened in a murine model of GI colonization. At three days post-inoculation, 27 genes were required by all three strains for colonization. Isogenic deletion mutants for three genes/operons (acrA, carAB, tatABCD) confirmed colonization defects in each of the three strains. Additionally, deletion of acrA reduced bile tolerance in vitro, while complementation restored both bile tolerance in vitro and colonization ability in vivo. Transposon insertion sequencing suggested that some genes were more important for colonization of one strain than the others. For example, deletion of the sucrose porin-encoding gene scrY resulted in a colonization defect in the carbapenemase-producing strain but not in the extended-spectrum beta-lactamase producer or the antibiotic-susceptible strain. These findings demonstrate that classical K. pneumoniae strains use both shared and strain-specific strategies to colonize the mouse GI tract. IMPORTANCE: Klebsiella pneumoniae is a common cause of difficult-to-treat infections due to its propensity to express resistance to many antibiotics. For example, carbapenem-resistant K. pneumoniae (CR-Kp) has been named an urgent threat by the United States Centers for Disease Control and Prevention. Gastrointestinal colonization of patients with K. pneumoniae has been linked to subsequent infection, making it a key process to control in prevention of multidrug-resistant infections. However, the bacterial factors which contribute to K. pneumoniae colonization are not well understood. Additionally, individual strains exhibit large amounts of genetic diversity, begging the question of whether some colonization factors are strain-dependent. This study identifies the enteric colonization factors of 3 classical strains using transposon mutant screens to define a core colonization program for K. pneumoniae as well as detecting strain-to-strain differences in colonization strategies.

Ethnic differences in stroke outcomes in Aotearoa New Zealand: A national linkage study.

BACKGROUND: Ethnic differences in post-stroke outcomes have been largely attributed to biological and socioeconomic characteristics resulting in differential risk factor profiles and stroke subtypes, but evidence is mixed. AIMS: This study assessed ethnic differences in stroke outcome and service access in New Zealand (NZ) and explored underlying causes in addition to traditional risk factors. METHODS: This national cohort study used routinely collected health and social data to compare post-stroke outcomes between NZ Europeans, Maori, Pacific Peoples, and Asians, adjusting for differences in baseline characteristics, socioeconomic deprivation, and stroke characteristics. First and principal stroke public hospital admissions during November 2017 to October 2018 were included (N = 6879). Post-stroke unfavorable outcome was defined as being dead, changing residence, or becoming unemployed. RESULTS: In total, 5394 NZ Europeans, 762 Maori, 369 Pacific Peoples, and 354 Asians experienced a stroke during the study period. Median age was 65 years for Maori and Pacific Peoples, and 71 and 79 years for Asians and NZ Europeans, respectively. Compared with NZ Europeans, Maori were more likely to have an unfavorable outcome at all three time-points (odds ratio (OR) = 1.6 (95% confidence interval (CI) = 1.3-1.9); 1.4 (1.2-1.7); 1.4 (1.2-1.7), respectively). Maori had increased odds of death at all time-points (1.7 (1.3-2.1); 1.5 (1.2-1.9); 1.7 (1.3-2.1)), change in residence at 3 and 6 months (1.6 (1.3-2.1); 1.3 (1.1-1.7)), and unemployment at 6 and 12 months (1.5 (1.1-2.1); 1.5 (1.1-2.1)). There was evidence of differences in post-stroke secondary prevention medication by ethnicity. CONCLUSION: We found ethnic disparities in care and outcomes following stroke which were independent of traditional risk factors, suggesting they may be attributable to stroke service delivery rather than patient factors.

Comparison of Stroke Care Costs in Urban and Nonurban Hospitals and Its Association With Outcomes in New Zealand: A Nationwide Economic Evaluation.

BACKGROUND: Although geographical differences in treatment and outcomes after stroke have been described, we lack evidence on differences in the costs of treatment between urban and nonurban regions. Additionally, it is unclear whether greater costs in one setting are justified given the outcomes achieved. We aimed to compare costs and quality-adjusted life years in people with stroke admitted to urban and nonurban hospitals in New Zealand. METHODS: Observational study of patients with stroke admitted to the 28 New Zealand acute stroke hospitals (10 in urban areas) recruited between May and October 2018. Data were collected up to 12 months poststroke including treatments in hospital, inpatient rehabilitation, other health service utilization, aged residential care, productivity, and health-related quality of life. Costs in New Zealand dollars were estimated from a societal perspective and assigned to the initial hospital that patients presented to. Unit prices for 2018 were obtained from government and hospital sources. Multivariable regression analyses were conducted when assessing differences between groups. RESULTS: Of 1510 patients (median age 78 years, 48% female), 607 presented to nonurban and 903 to urban hospitals. Mean hospital costs were greater in urban than nonurban hospitals ($13 191 versus $11 635, P=0.002), as were total costs to 12 months ($22 381 versus $17 217, P<0.001) and quality-adjusted life years to 12 months (0.54 versus 0.46, P<0.001). Differences in costs and quality-adjusted life years remained between groups after adjustment. Depending on the covariates included, costs per additional quality-adjusted life year in the urban hospitals compared to the nonurban hospitals ranged from $65 038 (unadjusted) to $136 125 (covariates: age, sex, prestroke disability, stroke type, severity, and ethnicity). CONCLUSIONS: Better outcomes following initial presentation to urban hospitals were associated with greater costs compared to nonurban hospitals. These findings may inform greater targeted expenditure in some nonurban hospitals to improve access to treatment and optimize outcomes.

The fecal microbiotas of women of Pacific and New Zealand European ethnicities are characterized by distinctive enterotypes that reflect dietary intakes and fecal water content.

Obesity is a complex, multifactorial condition that is an important risk factor for noncommunicable diseases including cardiovascular disease and type 2 diabetes. While prevention and management require a healthy and energy balanced diet and adequate physical activity, the taxonomic composition and functional attributes of the colonic microbiota may have a supplementary role in the development of obesity. The taxonomic composition and metabolic capacity of the fecal microbiota of 286 women, resident in Auckland New Zealand, was determined by metagenomic analysis. Associations with BMI (obese, nonobese), body fat composition, and ethnicity (Pacific, n = 125; NZ European women [NZE], n = 161) were assessed using regression analyses. The fecal microbiotas were characterized by the presence of three distinctive enterotypes, with enterotype 1 represented in both Pacific and NZE women (39 and 61%, respectively), enterotype 2 mainly in Pacific women (84 and 16%) and enterotype 3 mainly in NZE women (13 and 87%). Enterotype 1 was characterized mainly by the relative abundances of butyrate producing species, Eubacterium rectale and Faecalibacterium prausnitzii, enterotype 2 by the relative abundances of lactic acid producing species, Bifidobacterium adolescentis, Bifidobacterium bifidum, and Lactobacillus ruminis, and enterotype 3 by the relative abundances of Subdoligranulum sp., Akkermansia muciniphila, Ruminococcus bromii, and Methanobrevibacter smithii. Enterotypes were also associated with BMI, visceral fat %, and blood cholesterol. Habitual food group intake was estimated using a 5 day nonconsecutive estimated food record and a 30 day, 220 item semi-quantitative Food Frequency Questionnaire. Higher intake of 'egg' and 'dairy' products was associated with enterotype 3, whereas 'non-starchy vegetables', 'nuts and seeds' and 'plant-based fats' were positively associated with enterotype 1. In contrast, these same food groups were inversely associated with enterotype 2. Fecal water content, as a proxy for stool consistency/colonic transit time, was associated with microbiota taxonomic composition and gene pools reflective of particular bacterial biochemical pathways. The fecal microbiotas of women of Pacific and New Zealand European ethnicities are characterized by distinctive enterotypes, most likely due to differential dietary intake and fecal consistency/colonic transit time. These parameters need to be considered in future analyses of human fecal microbiotas.

Long working hours, sedentary work, noise, night shifts and risk of ischaemic heart disease.

OBJECTIVE: Ischaemic heart disease (IHD) is a leading cause of death in Western countries. The aim of this study was to examine the associations between occupational exposure to loud noise, long working hours, shift work, and sedentary work and IHD. METHODS: This data linkage study included all New Zealanders employed and aged 20-64 years at the time of the 2013 census, followed up for incident IHD between 2013 and 2018 based on hospitalisation, prescription and death records. Occupation and number of working hours were obtained from the census, and exposure to sedentary work, loud noise and night shift work was assessed using New Zealand job exposure matrices. HRs were calculated for males and females using Cox regression adjusted for age, socioeconomic status, smoking and ethnicity. RESULTS: From the 8 11 470 males and 7 83 207 females employed at the time of the census, 15 012 male (1.9%) and 5595 female IHD cases (0.7%) were identified. For males, there was a modestly higher risk of IHD for the highest category (>90 dBA) of noise exposure (HR 1.19; 95% CI 1.07 to 1.33), while for females exposure prevalence was too low to calculate an HR. Night shift work was associated with IHD for males (HR 1.10; 95% CI 1.05 to 1.14) and females (HR 1.25; 95% CI 1.17 to 1.34). The population attributable fractions for night shift work were 1.8% and 4.6%, respectively. No clear associations with working long hours and sedentary work were observed. CONCLUSIONS: This study suggests that occupational exposures to high levels of noise and night shift work might be associated with IHD risk.

Patient, carer and health worker perspectives of stroke care in New Zealand: a mixed methods survey.

PURPOSE: It is important to understand how consumers (person with stroke/family member/carer) and health workers perceive stroke care services. MATERIALS AND METHODS: Consumers and health workers from across New Zealand were surveyed on perceptions of stroke care, access barriers, and views on service centralisation. Quantitative data were summarised using descriptive statistics whilst thematic analysis was used for free-text answers. RESULTS: Of 149 consumers and 79 health workers invited to complete a survey, 53 consumers (36.5%) and 41 health workers (51.8%) responded. Overall, 40/46 (87%) consumers rated stroke care as 'good/excellent' compared to 24/41 (58.6%) health workers. Approximately 72% of consumers preferred to transfer to a specialised hospital. We identified three major themes related to perceptions of stroke care: 1) 'variability in care by stage of treatment'; 2) 'impact of communication by health workers on care experience'; and 3) 'inadequate post-acute services for younger patients'. Four access barrier themes were identified: 1) 'geographic inequities'; 2) 'knowing what is available'; 3) 'knowledge about stroke and available services'; and 4) 'healthcare system factors'. CONCLUSIONS: Perceptions of stroke care differed between consumers and health workers, highlighting the importance of involving both in service co-design. Improving communication, post-hospital follow-up, and geographic equity are key areas for improvement.Implications for rehabilitationProvision of detailed information on stroke recovery and available services in the community is recommended.Improvements in the delivery of post-hospital stroke care are required to optimise stroke care, with options including routine phone follow up appointments and wider development of early supported discharge services.Stroke rehabilitation services should continue to be delivered 'close to home' to allow community integration.Telehealth is a likely enabler to allow specialist urban clinicians to support non-urban clinicians, as well as increasing the availability and access of community rehabilitation.

Functional and Structural Characterization of OXA-935, a Novel OXA-10-Family ß-Lactamase from Pseudomonas aeruginosa.

Resistance to antipseudomonal penicillins and cephalosporins is often driven by the overproduction of the intrinsic ß-lactamase AmpC. However, OXA-10-family ß-lactamases are a rich source of resistance in Pseudomonas aeruginosa. OXA ß-lactamases have a propensity for mutation that leads to extended spectrum cephalosporinase and carbapenemase activity. In this study, we identified isolates from a subclade of the multidrug-resistant (MDR) high risk P. aeruginosa clonal complex CC446 with a resistance to ceftazidime. A genomic analysis revealed that these isolates harbored a plasmid containing a novel allele of blaOXA-10, named blaOXA-935, which was predicted to produce an OXA-10 variant with two amino acid substitutions: an aspartic acid instead of a glycine at position 157 and a serine instead of a phenylalanine at position 153. The G157D mutation, present in OXA-14, is associated with the resistance of P. aeruginosa to ceftazidime. Compared to OXA-14, OXA-935 showed increased catalytic efficiency for ceftazidime. The deletion of blaOXA-935 restored the sensitivity to ceftazidime, and susceptibility profiling of P. aeruginosa laboratory strains expressing blaOXA-935 revealed that OXA-935 conferred ceftazidime resistance. To better understand the impacts of the variant amino acids, we determined the crystal structures of OXA-14 and OXA-935. Compared to OXA-14, the F153S mutation in OXA-935 conferred increased flexibility in the omega (Ω) loop. Amino acid changes that confer extended spectrum cephalosporinase activity to OXA-10-family ß-lactamases are concerning, given the rising reliance on novel ß-lactam/ß-lactamase inhibitor combinations, such as ceftolozane-tazobactam and ceftazidime-avibactam, to treat MDR P. aeruginosa infections.

Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates.

BACKGROUND: Klebsiella pneumoniae strains have been divided into two major categories: classical K. pneumoniae, which are frequently multidrug-resistant and cause hospital-acquired infections in patients with impaired defenses, and hypervirulent K. pneumoniae, which cause severe community-acquired and disseminated infections in normal hosts. Both types of infections may lead to bacteremia and are associated with significant morbidity and mortality. The relative burden of these two types of K. pneumoniae among bloodstream isolates within the United States is not well understood. METHODS: We evaluated consecutive K. pneumoniae isolates cultured from the blood of hospitalized patients at Northwestern Memorial Hospital (NMH) in Chicago, Illinois between April 2015 and April 2017. Bloodstream isolates underwent whole genome sequencing, and sequence types (STs), capsule loci (KLs), virulence genes, and antimicrobial resistance genes were identified in the genomes using the bioinformatic tools Kleborate and Kaptive. Patient demographic, comorbidity, and infection information, as well as the phenotypic antimicrobial resistance of the isolates were extracted from the electronic health record. Candidate hypervirulent isolates were tested in a murine model of pneumonia, and their plasmids were characterized using long-read sequencing. We also extracted STs, KLs, and virulence and antimicrobial resistance genes from the genomes of bloodstream isolates submitted from 33 United States institutions between 2007 and 2021 to the National Center for Biotechnology Information (NCBI) database. RESULTS: Consecutive K. pneumoniae bloodstream isolates (n = 104, one per patient) from NMH consisted of 75 distinct STs and 51 unique capsule loci. The majority of these isolates (n = 58, 55.8%) were susceptible to all tested antibiotics except ampicillin, but 17 (16.3%) were multidrug-resistant. A total of 32 (30.8%) of these isolates were STs of known high-risk clones, including ST258 and ST45. In particular, 18 (17.3%) were resistant to ceftriaxone (of which 17 harbored extended-spectrum beta-lactamase genes) and 9 (8.7%) were resistant to meropenem (all of which harbored a carbapenemase genes). Four (3.8%) of the 104 isolates were hypervirulent K. pneumoniae, as evidenced by hypermucoviscous phenotypes, high levels of virulence in a murine model of pneumonia, and the presence of large plasmids similar to characterized hypervirulence plasmids. These isolates were cultured from patients who had not recently traveled to Asia. Two of these hypervirulent isolates belonged to the well characterized ST23 lineage and one to the re-emerging ST66 lineage. Of particular concern, two of these isolates contained plasmids with tra conjugation loci suggesting the potential for transmission. We also analyzed 963 publicly available genomes of K. pneumoniae bloodstream isolates from locations within the United States. Of these, 465 (48.3%) and 760 (78.9%) contained extended-spectrum beta-lactamase genes or carbapenemase genes, respectively, suggesting a bias towards submission of antibiotic-resistant isolates. The known multidrug-resistant high-risk clones ST258 and ST307 were the predominant sequence types. A total of 32 (3.3%) of these isolates contained aerobactin biosynthesis genes and 26 (2.7%) contained at least two genetic features of hvKP strains, suggesting elevated levels of virulence. We identified 6 (0.6%) isolates that were STs associated with hvKP: ST23 (n = 4), ST380 (n = 1), and ST65 (n = 1). CONCLUSIONS: Examination of consecutive isolates from a single center demonstrated that multidrug-resistant high-risk clones are indeed common, but a small number of hypervirulent K. pneumoniae isolates were also observed in patients with no recent travel history to Asia, suggesting that these isolates are undergoing community spread in the United States. A larger collection of publicly available bloodstream isolate genomes also suggested that hypervirulent K. pneumoniae strains are present but rare in the USA; however, this collection appears to be heavily biased towards highly antibiotic-resistant isolates (and correspondingly away from hypervirulent isolates).

Barriers to optimal stroke service care and solutions: a qualitative study engaging people with stroke and their whanau.

AIM: The aim of this study was to explore the perspectives of people with stroke and their whanau on barriers to accessing best practice care across Aotearoa, and to brainstorm potential solutions. METHOD: We conducted ten focus groups nationwide and completed a thematic analysis. RESULTS: Analysis of the data collected from the focus groups identified five themes: (1) inconsistencies in stroke care; (2) importance of effective communication; (3) the role of whanau support; (4) the need for more person rather than stroke centred processes; and (5) experienced inequities. Participants also identified potential solutions. CONCLUSION: Key recommendations include the need for improved access to stroke unit care for rural residents, improved post-discharge support and care coordination involving the whanau, improved communication across the patient journey, and a concerted effort to improve culturally safe care. Next step is to implement and monitor these recommendations.

Geographic Disparities in Stroke Outcomes and Service Access: A Prospective Observational Study.

BACKGROUND AND OBJECTIVE: International evidence shows that patients treated at non-urban hospitals experience poorer access to key stroke interventions. Evidence whether this results in poorer outcomes is conflicting and generally based on administrative or voluntary registry data. The aim of this study was to use prospective high-quality comprehensive nationwide patient level data to investigate the association between hospital geography and stroke patient outcomes and access to best practice stroke care in New Zealand. METHODS: This is a prospective, multi-centre, nationally representative observational study involving all 28 New Zealand acute stroke hospitals (18 non-urban), and affiliated rehabilitation and community services. Consecutive adults admitted to the hospital with acute stroke between 1 May and 31 October 2018 were captured. Outcomes included functional outcome (modified Rankin Scale (mRS) shift analysis), functional independence (mRS scores 0-2), quality of life (EQ5D-3L), stroke/vascular events, and death at 3, 6, and 12 months and proportion accessing thrombolysis, thrombectomy, stroke units, key investigations, secondary prevention, and inpatient/community rehabilitation. Results were adjusted for age, sex, ethnicity, stroke severity/type, co-morbidities, baseline function, and differences in baseline characteristics. RESULTS: Overall, 2,379 patients were eligible (mean (standard deviation) age 75 (13.7); 51.2% male; 1,430 urban; 949 non-urban). Patients treated at non-urban hospitals were more likely to score in a higher mRS category (greater disability) at three (aOR=1.28, 1.07-1.53), six (aOR=1.33, 1.07-1.65) and twelve months (aOR=1.31, 1.06-1.62) and were more likely to have died (aOR=1.57, 1.17-2.12) or experienced recurrent stroke and vascular events at 12 months (aOR=1.94, 1.14-3.29 and aOR=1.65, 1.09-2.52). Fewer non-urban patients received recommended stroke interventions including endovascular thrombectomy (aOR=0.25, 95% confidence interval 0.13-0.49), acute stroke unit care (aOR=0.60, 0.49-0.73), antiplatelet prescriptions (aOR=0.72, 0.58-0.88), ≥60 minutes daily physical therapy (aOR=0.55, 0.40-0.77) and community rehabilitation (aOR=0.69, 0.56-0.84). DISCUSSION: Patients managed at non-urban hospitals experience poorer stroke outcomes and reduced access to key stroke interventions across the entire care continuum. Efforts to improve access to high quality stroke care in non-urban hospitals should be a priority.

A longitudinal linkage study of occupation and ischaemic heart disease in the general and Maori populations of New Zealand.

OBJECTIVES: Occupation is a poorly characterised risk factor for cardiovascular disease (CVD) with females and indigenous populations under-represented in most research. This study assessed associations between occupation and ischaemic heart disease (IHD) in males and females of the general and Maori (indigenous people of NZ) populations of New Zealand (NZ). METHODS: Two surveys of the NZ adult population (NZ Workforce Survey (NZWS); 2004-2006; n = 3003) and of the Maori population (NZWS Maori; 2009-2010; n = 2107) with detailed occupational histories were linked with routinely collected health data and followed-up until December 2018. Cox regression was used to calculate hazard ratios (HR) for IHD and "ever-worked" in any of the nine major occupational groups or 17 industries. Analyses were controlled for age, deprivation and smoking, and stratified by sex and survey. RESULTS: 'Plant/machine operators and assemblers' and 'elementary occupations' were positively associated with IHD in female Maori (HR 2.2, 95%CI 1.2-4.1 and HR 2.0, 1.1-3.8, respectively) and among NZWS males who had been employed as 'plant/machine operators and assemblers' for 10+ years (HR 1.7, 1.2-2.8). Working in the 'manufacturing' industry was also associated with IHD in NZWS females (HR 1.9, 1.1-3.7), whilst inverse associations were observed for 'technicians and associate professionals' (HR 0.5, 0.3-0.8) in NZWS males. For 'clerks', a positive association was found for NZWS males (HR 1.8, 1.2-2.7), whilst an inverse association was observed for Maori females (HR 0.4, 0.2-0.8). CONCLUSION: Associations with IHD differed significantly across occupational groups and were not consistent across males and females or for Maori and the general population, even within the same occupational groups, suggesting that current knowledge regarding the association between occupation and IHD may not be generalisable across different population groups.

The impact of ethnicity on stroke care access and patient outcomes: a New Zealand nationwide observational study.

BACKGROUND: Ethnic inequities in stroke care access have been reported internationally but the impact on outcomes remains unclear. In New Zealand, data on ethnic stroke inequities and resultant effects on outcomes are generally limited and conflicting. METHODS: In a prospective, nationwide, multi-centre observational study, we recruited consecutive adult patients with confirmed stroke from 28 hospitals between 1 May and 31 October 2018. Patient outcomes: favourable functional outcomes (modified Rankin Scale 0-2); quality of life (EQ-5D-3L); stroke/vascular events; and death at three, six and 12 months. Process measures: access to reperfusion therapies, stroke-units, investigations, secondary prevention, rehabilitation. Multivariate regression analyses assessed associations between ethnicity and outcomes and process measures. FINDINGS: The cohort comprised 2,379 patients (median age 78 (IQR 66-85); 51·2% male; 76·7% European, 11·5% Maori, 4·8% Pacific peoples, 4·8% Asian). Non-Europeans were younger, had more risk factors, had reduced access to acute stroke units (aOR=0·78, 95%CI, 0·60-0·97), and were less likely to receive a swallow screen within 24 hours of arrival (aOR=0·72, 0·53-0·99) or MRI imaging (OR=0·66, 0·52-0·85). Maori were less frequently prescribed anticoagulants (OR=0·68, 0·47-0·98). Pacific peoples received greater risk factor counselling. Fewer non-Europeans had a favourable mRS score at three (aOR=0·67, 0·47-0·96), six (aOR=0·63, 0·40-0·98) and 12 months (aOR=0·56, 0·36-0·88), and more Maori had died by 12 months (aOR=1·76, 1·07-2·89). INTERPRETATION: Non-Europeans, especially Maori, had poorer access to key stroke interventions and experience poorer outcomes. Further optimisation of stroke care targeting high-priority populations are needed to achieve equity. FUNDING: New Zealand Health Research Council (HRC17/037).

Ischaemic Heart Disease and Occupational Exposures: A Longitudinal Linkage Study in the General and Maori Populations of New Zealand.

OBJECTIVES: This study assessed associations between occupational exposures and ischaemic heart disease (IHD) for males and females in the general and Maori populations (indigenous people of New Zealand). METHODS: Two surveys of the general adult [New Zealand Workforce Survey (NZWS); 2004-2006; n = 3003] and Maori population (Maori NZWS; 2009-2010; n = 2107), with information on occupational exposures, were linked with administrative health data and followed-up until December 2018. Cox proportional hazards regression (adjusted for age, deprivation, and smoking) was used to assess associations between organizational factors, stress, and dust, chemical and physical exposures, and IHD. RESULTS: Dust [hazard ratio (HR) 1.6, 95%CI 1.1-2.4], smoke or fumes (HR 1.5, 1.0-2.3), and oils and solvents (HR 1.5, 1.0-2.3) were associated with IHD in NZWS males. A high frequency of awkward or tiring hand positions was associated with IHD in both males and females of the NZWS (HRs 1.8, 1.1-2.8 and 2.4, 1.1-5.0, respectively). Repetitive tasks and working at very high speed were associated with IHD among NZWS females (HRs 3.4, 1.1-10.4 and 2.6, 1.2-5.5, respectively). Maori NZWS females working with vibrating tools and those exposed to a high frequency of loud noise were more likely to experience IHD (HRs 2.3, 1.1-4.8 and 2.1, 1.0-4.4, respectively). Exposure to multiple dust and chemical factors was associated with IHD in the NZWS males, as was exposure to multiple physical factors in males and females of the NZWS. CONCLUSIONS: Exposures associated with an elevated IHD risk included dust, smoke or fumes, oils and solvents, awkward grip or hand movements, carrying out repetitive tasks, working at very high speed, loud noise, and working with tools that vibrate. Results were not consistently observed for males and females and between the general and Maori populations.

Objectively Measured Physical Activity Is Associated With Body Composition and Metabolic Profiles of Pacific and New Zealand European Women With Different Metabolic Disease Risks.

Objective: To assess associations between physical activity (PA), body composition, and biomarkers of metabolic health in Pacific and New Zealand European (NZE) women who are known to have different metabolic disease risks. Methods: Pacific (n = 142) or NZE (n = 162) women aged 18-45 years with a self-reported body mass index (BMI) of either 18.5-25.0 kg⋅m-2 or ≥30.0 kg⋅m-2 were recruited and subsequently stratified as either low (<35%) or high (≥35%) BF%, with approximately half of each group in either category. Seven-day accelerometery was used to assess PA levels. Fasting blood was analysed for biomarkers of metabolic health, and whole body dual-energy X-ray absorptiometry (DXA) was used to estimate body composition. Results: Mean moderate-to-vigorous physical activity (MVPA; min⋅day-1) levels differed between BF% (p < 0.05) and ethnic (p < 0.05) groups: Pacific high- 19.1 (SD 15.2) and low-BF% 26.3 (SD 15.6) and NZE high- 30.5 (SD 19.1) and low-BF% 39.1 (SD 18.4). On average Pacific women in the low-BF% group engaged in significantly less total PA when compared to NZE women in the low-BF% group (133 cpm); no ethnic difference in mean total PA (cpm) between high-BF% groups were observed: Pacific high- 607 (SD 185) and low-BF% 598 (SD 168) and NZE high- 674 (SD 210) and low-BF% 731 (SD 179). Multiple linear regression analysis controlling for age and deprivation showed a significant inverse association between increasing total PA and fasting plasma insulin among Pacific women; every 100 cpm increase in total PA was associated with a 6% lower fasting plasma insulin; no significant association was observed in NZE women. For both Pacific and NZE women, there was an 8% reduction in fasting plasma insulin for every 10-min increase in MVPA (p ≤ 0.05). Conclusion: Increases in total PA and MVPA are associated with lower fasting plasma insulin, thus indicating a reduction in metabolic disease risk. Importantly, compared to NZE, the impact of increased total PA on fasting insulin may be greater in Pacific women. Considering Pacific women are a high metabolic disease risk population, these pre-clinical responses to PA may be important in this population; indicating promotion of PA in Pacific women should remain a priority.

Reducing Ethnic and Geographic Inequities to Optimise New Zealand Stroke Care (REGIONS Care): Protocol for a Nationwide Observational Study.

BACKGROUND: Stroke systems of care differ between larger urban and smaller rural settings and it is unclear to what extent this may impact on patient outcomes. Ethnicity influences stroke risk factors and care delivery as well as patient outcomes in nonstroke settings. Little is known about the impact of ethnicity on poststroke care, especially in Maori and Pacific populations. OBJECTIVE: Our goal is to describe the protocol for the Reducing Ethnic and Geographic Inequities to Optimise New Zealand Stroke Care (REGIONS Care) study. METHODS: This large, nationwide observational study assesses the impact of rurality and ethnicity on best practice stroke care access and outcomes involving all 28 New Zealand hospitals caring for stroke patients, by capturing every stroke patient admitted to hospital during the 2017-2018 study period. In addition, it explores current access barriers through consumer focus groups and consumer, carer, clinician, manager, and policy-maker surveys. It also assesses the economic impact of care provided at different types of hospitals and to patients of different ethnicities and explores the cost-efficacy of individual interventions and care bundles. Finally, it compares manual data collection to routine health administrative data and explores the feasibility of developing outcome models using only administrative data and the cost-efficacy of using additional manually collected registry data. Regarding sample size estimates, in Part 1, Study A, 2400 participants are needed to identify a 10% difference between up to four geographic subgroups at 90% power with an α value of .05 and 10% to 20% loss to follow-up. In Part 1, Study B, a sample of 7645 participants was expected to include an estimated 850 Maori and 419 Pacific patients and to provide over 90% and over 80% power, respectively. Regarding Part 2, 50% of the patient or carer surveys, 40 provider surveys, and 10 focus groups were needed to achieve saturation of themes. The main outcome is the modified Rankin Scale (mRS) score at 3 months. Secondary outcomes include mRS scores; EQ-5D-3L (5-dimension, 3-level EuroQol questionnaire) scores; stroke recurrence; vascular events; death; readmission at 3, 6, and 12 months; cost of care; and themes around access barriers. RESULTS: The study is underway, with national and institutional ethics approvals in place. A total of 2379 patients have been recruited for Part 1, Study A; 6837 patients have been recruited for Part 1, Study B; 10 focus groups have been conducted and 70 surveys have been completed in Part 2. Data collection has essentially been completed, including follow-up assessment; however, primary and secondary analyses, data linkage, data validation, and health economics analysis are still underway. CONCLUSIONS: The methods of this study may provide the basis for future epidemiological studies that will guide care improvements in other countries and populations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25374.

New Zealand hospital stroke service provision.

AIM: To describe stroke services currently offered in New Zealand hospitals and compare service provision in urban and non-urban settings. METHOD: An online questionnaire was sent to stroke lead clinicians at all New Zealand District Health Boards (DHBs). Questions covered number and location of stroke inpatients, stroke service configuration, use of guidelines/protocols, staffing mix, access to staff education, and culture appropriate care. RESULTS: There were responses from all 20 DHBs. Differences between urban and non-urban hospitals included: access to acute stroke units (55.6% non-urban vs 100% urban; p=0.013), stroke clinical nurse specialists (50% vs 90%; p=0.034), stroke clot retrieval (38.9% vs 80%; p=0.037) and Pacific support services (55.6% vs 100%; p=0.030). There were also differences in carer training (66.7% non-urban vs 100% urban; p=0.039) and goal-specific rehabilitation plans in the community (61.1% vs 100%; p=0.023). Access to TIA services, stroke rehabilitation units, early supported discharge, psychologists, continuing staff education, and culturally responsive stroke care were suboptimal irrespective of hospital location. CONCLUSION: Hospital location is associated with differences in stroke services provision across New Zealand and ongoing work is required to optimise consistent access to best practice care. These results, in conjunction with an ongoing (REGIONS Care) study, will be used to determine whether this affects patient outcomes.

The Prevalence of Cardiovascular Risk Factors in Different Occupational Groups in New Zealand.

OBJECTIVES: Although cardiovascular disease (CVD) risk has been shown to differ between occupations, few studies have specifically evaluated the distribution of known CVD risk factors across occupational groups. This study assessed CVD risk factors in a range of occupational groups in New Zealand, stratified by sex and ethnicity. METHODS: Two probability-based sample surveys of the general New Zealand adult population (2004-2006; n = 3003) and of the indigenous people of New Zealand (Maori; 2009-2010; n = 2107), for which occupational histories and lifestyle factors were collected, were linked with routinely collected health data. Smoking, body mass index, deprivation, diabetes, high blood pressure, and high cholesterol were dichotomized and compared between occupational groups using age-adjusted logistic regression. RESULTS: The prevalence of all known CVD risk factors was greater in the Maori survey than the general population survey, and in males compared with females. In general for men and women in both surveys 'Plant and machine operators and assemblers' and 'Elementary workers' were more likely to experience traditional CVD risk factors, while 'Professionals' were less likely to experience these risk factors. 'Clerks' were more likely to have high blood pressure and male 'Agricultural and fishery workers' in the general survey were less likely to have high cholesterol, but this was not observed in the Maori survey. Male Maori 'Trades workers' were less likely to have high cholesterol and were less obese, while for the general population survey, this was not observed. CONCLUSIONS: This study showed differences in the distribution of known CVD risk factors across occupational groups, as well as between ethnic groups and males and females.