Bronchiectasis is associated with delayed diagnosis and adverse outcomes in the New Zealand Common Variable Immunodeficiency Disorders cohort study.

Common variable immunodeficiency disorders (CVID) are multi-system disorders where target organ damage is mediated by infective, autoimmune and inflammatory processes. Bronchiectasis is probably the most common disabling complication of CVID. The risk factors for bronchiectasis in CVID patients are incompletely understood. The New Zealand CVID study (NZCS) is a nationwide longitudinal observational study of adults, which commenced in 2006. In this analysis, the prevalence and risk factors for bronchiectasis were examined in the NZCS. After informed consent, clinical and demographic data were obtained with an interviewer-assisted questionnaire. Linked electronic clinical records and laboratory results were also reviewed. Statistical methods were applied to determine if variables such as early-onset disease, delay in diagnosis and increased numbers of infections were associated with greater risk of bronchiectasis. One hundred and seven adult patients with a diagnosis of CVID are currently enrolled in the NZCS, comprising approximately 70% of patients known to have CVID in New Zealand. Fifty patients (46·7%) had radiologically proven bronchiectasis. This study has shown that patients with compared to those without bronchiectasis have an increased mortality at a younger age. CVID patients with bronchiectasis had a greater number of severe infections consequent to early-onset disease and delayed diagnosis. Indigenous Maori have a high prevalence of CVID and a much greater burden of bronchiectasis compared to New Zealand Europeans. Diagnostic latency has not improved during the study period. Exposure to large numbers of infections because of early-onset disease and delayed diagnosis was associated with an increased risk of bronchiectasis. Earlier diagnosis and treatment of CVID may reduce the risk of bronchiectasis and premature death in some patients.

The association between labour epidural case volume and the rate of accidental dural puncture.

Accidental dural puncture is a recognised complication of labour epidural placement and can cause a debilitating headache. We examined the association between labour epidural case volume and accidental dural puncture rate in specialist anaesthetists and anaesthesia trainees. We performed a retrospective cohort study of labour epidural and combined spinal-epidural nerve blocks performed between 1 July 2013 and 31 December 2017 at Waitemata District Health Board, Auckland, New Zealand. The mean (SD) annual number of obstetric epidural and combined spinal-epidural procedures for high-case volume specialists was 44.2 (15.0), and for low-case volume specialists was 10.0 (6.8), after accounting for caesarean section combined spinal-epidural procedures. Analysis of 7976 labour epidural and combined spinal-epidural procedure records revealed a total of 92 accidental dural punctures (1.2%). The accidental dural puncture rate (95%CI) in high-case volume specialists was 0.6% (0.4-0.9%) and in low-case volume specialists 2.4% (1.4-3.9%), indicating probable skill decay. The odds of accidental dural puncture were 3.77 times higher for low- compared with high-case volume specialists (95%CI 1.72-8.28, p = 0.001). Amongst trainees, novices had a significantly higher accidental dural puncture complication rate (3.1%) compared with registrars (1.2%), OR (95%CI) 0.39 (0.18-0.84), p = 0.016, or fellows (1.1%), 0.35 (0.16-0.76), p = 0.008. Accidental dural puncture complication rates decreased once trainees progressed past the 'novice' training stage.

Benchmarking nurse outcomes in Australian Magnet® hospitals: cross-sectional survey.

BACKGROUND: Positive reports of nursing-related outcomes such as quality nursing care, nursing engagement with work and good practice environment are crucial in attaining and maintaining Magnet® designation. The majority of Magnet®-designated organisations (N = 482) are in the USA, with their aggregate nursing outcomes widely published as benchmark data. Australian Magnet® outcomes have not been aggregated or published to date. METHODS: The aims are to benchmark educational preparation, occupational burnout, job satisfaction, intention to leave and working environment of nurses in Australian Magnet®-designated facilities and to determine the reliability of the Practice Environment Scale-Australia.The design is a cross-sectional multisite survey set in all three Australian Magnet®-designated organisations.The demographics included age, gender, level of education, years in practice, level of seniority and position title. Two items measured job satisfaction and intent to stay in current employment. The Maslach Burnout Inventory explored the three domains of nursing engagement: depersonalisation, personal achievement and emotional exhaustion. The Australian version of the Practice Environment Scale interrogated participants' perceptions of their work environments. RESULTS: 2004 nurses participated (response rate 45.9%). Respondents' mean age was 39.2 years (range 20-72). They were predominantly female and had worked in their current facility for more than 5 years. Eighty five percent had a minimum of a Bachelor's degree. Eighty-six percent of respondents were satisfied or very satisfied with their current position. Eighty eight percent had no intention of leaving their current employer within the next 12 months. Participants rated their hospitals highly in all domains of the practice environment. Respondents reported less burnout in the personal accomplishment and depersonalisation domains than in the emotional exhaustion domain, in which they reported average levels of burnout. The internal consistency of the Practice Environment Scale-Australia was confirmed in this sample (Cronbach α's 0.87-0.9 for subscales and 0.89 for composite score). CONCLUSION: In this paper, we present nursing outcome data from all Australian Magnet® hospitals for the first time. This provides a benchmark that facilitates comparison with nursing outcomes published by Australian non-Magnet® hospitals and with international Magnet® organisations.

Genetic association analysis of vitamin D pathway with obesity traits.

OBJECTIVE: Observational studies have examined the link between vitamin D deficiency and obesity traits. Some studies have reported associations between vitamin D pathway genes such as VDR, GC and CYP27B1 with body mass index (BMI) and waist circumference (WC); however, the findings have been inconsistent. Therefore, we investigated the involvement of vitamin D metabolic pathway genes in obesity-related traits in a large population-based study. METHODS: We undertook a comprehensive analysis between 100 tagging single nucleotide polymorphisms (tagSNPs) in genes encoding for DHCR7, CYP2R1, VDBP, CYP27B1, CYP27A1, CYP24A1, VDR and RXRG, and obesity traits in 5224 participants (aged 45 years) in the 1958 British birth cohort (1958BC). We further extended our analyses to investigate the associations between SNPs and obesity traits using the summary statistics from the GIANT (Genetic Investigation of Anthropometric Traits) consortium (n=123 865). RESULTS: In the 1958BC (n=5224), after Bonferroni correction, none of the tagSNPs were associated with obesity traits except for one tagSNP from CYP24A1 that was associated with waist-hip ratio (WHR) (rs2296239, P=0.001). However, the CYP24A1 SNP was not associated with BMI-adjusted WHR (WHRadj) in the 1958BC (rs2296239, P=1.00) and GIANT results (n=123 865, P=0.18). There was also no evidence for an interaction between the tagSNPs and obesity on BMI, WC, WHR and WHRadj in the 1958BC. In the GIANT consortium, none of the tagSNPs were associated with obesity traits. CONCLUSIONS: Despite a very large study, our findings suggest that the vitamin D pathway genes are unlikely to have a major role in obesity-related traits in the general population.

Evidence for a genetic interaction in allergy-related responsiveness to vitamin D deficiency.

BACKGROUND: The hormonal form of vitamin D affects both adaptive and innate immune functions involved in the development of allergies. Certain genotypes have been seen to alter the association between vitamin D deficiency (VDD) and the risk of food sensitization in children. METHODS: We examined 27 functional single nucleotide polymorphisms (SNPs) in/near selected candidate genes for association with total immunoglobulin E (IgE) and effect modification by 25-hydroxyvitamin D in the 1958 British birth cohort (aged 45 years, n = 4921). A cut-off value of 50 nmol/L was used to define VDD. RESULTS: Four SNPs (in FCER1A, IL13, and CYP24A1) and three SNPs (in IL4 and CYP24A1) were associated with total IgE and specific IgE, respectively, after correction for multiple testing. As in a previous study, MS4A2 (rs512555, P(interaction) = 0.04) and IL4 (rs2243250, P(interaction) = 0.02), and their composite score (P(interaction) = 0.009) modified the association between VDD and allergy-related outcome. Vitamin D deficiency was associated with higher total IgE only in the carriers of the 'C' allele (IL4), which is present in 86% of white Europeans, while only 26% of Chinese and <20% of some African populations are carriers. CONCLUSIONS: Our study on white European adults was consistent with a previous study on children from largely non-white ethnic groups, suggesting that IL4 and MS4A2 genotypes modify the association between VDD and allergy risk. The risk allele in IL4 is present in nearly 90% of white Europeans, while less than a quarter are carriers in some other populations, highlighting the need to consider possible ethnic differences in allergy-related responsiveness to VDD.

Adult height, coronary heart disease and stroke: a multi-locus Mendelian randomization meta-analysis.

Background: We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis. Methods: We developed an allele score based on 69 single nucleotide polymorphisms (SNPs) associated with adult height, identified by the IBCCardioChip, and used it for IV analysis against cardiovascular risk factors and events in 21 studies and 60 028 participants. IV analysis on CHD was supplemented by summary data from 180 height-SNPs from the GIANT consortium and their corresponding CHD estimates derived from CARDIoGRAMplusC4D. Results: IV estimates from IBCCardioChip and GIANT-CARDIoGRAMplusC4D showed that a 6.5-cm increase in height reduced the odds of CHD by 10% [odds ratios 0.90; 95% confidence intervals (CIs): 0.78 to 1.03 and 0.85 to 0.95, respectively],which agrees with the estimate from the Emerging Risk Factors Collaboration (hazard ratio 0.93; 95% CI: 0.91 to 0.94). IV analysis revealed no association with stroke (odds ratio 0.97; 95% CI: 0.79 to 1.19). IV analysis showed that a 6.5-cm increase in height resulted in lower levels of body mass index ( P < 0.001), triglycerides ( P < 0.001), non high-density (non-HDL) cholesterol ( P < 0.001), C-reactive protein ( P = 0.042), and systolic blood pressure ( P = 0.064) and higher levels of forced expiratory volume in 1 s and forced vital capacity ( P < 0.001 for both). Conclusions: Taller individuals have a lower risk of CHD with potential explanations being that taller people have a better lung function and lower levels of body mass index, cholesterol and blood pressure.

25-hydroxyvitamin D, APOE ɛ4 genotype and cognitive function: findings from the 1958 British birth cohort.

Both high and low vitamin D statuses have been associated with lower memory function. Apolipoprotein E (APOE) ɛ4 alleles have been associated with reduced memory function, and separately with higher vitamin D concentrations. This report aims to examine if the presence of APOE ɛ4 alleles contributes to the relationship between vitamin D and memory function. A total of 4848 (46% female) participants from the 1958 British birth cohort had information on APOE genotypes and completed memory tests at 50 years, where 4644 also had 25-hydroxyvitamin D (25(OH)D) concentrations measured at 45 years. Both low and high 25(OH)D concentrations were associated with lower memory function after adjustment for number of APOE ɛ4 alleles (P curvature=0.02). There was evidence of interaction between APOE ɛ4 and 25(OH)D, suggesting the association between 25(OH)D concentrations and memory function is different for those with two APOE ɛ4 alleles compared with those with zero or one APOE ɛ4 alleles (recessive model P interaction=0.01). Among participants with two APOE ɛ4 alleles, higher 25(OH)D concentrations were associated with higher memory function, whereas in others, memory scores were slightly lower for individuals with higher versus lower concentrations. Further studies are required to replicate these findings.