Cardiovascular outcomes 50 years after antenatal exposure to betamethasone: Follow-up of a randomised double-blind, placebo-controlled trial.

BACKGROUND: Antenatal corticosteroids for women at risk of preterm birth reduce neonatal morbidity and mortality, but there is limited evidence regarding their effects on long-term health. This study assessed cardiovascular outcomes at 50 years after antenatal exposure to corticosteroids. METHODS AND FINDINGS: We assessed the adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (RDS) (1969 to 1974). The first 717 mothers received 2 intramuscular injections of 12 mg betamethasone or placebo 24 h apart and the subsequent 398 received 2 injections of 24 mg betamethasone or equivalent volume of placebo. Follow-up included a health questionnaire and consent to access administrative data sources. The co-primary outcomes were the prevalence of cardiovascular risk factors (any of hypertension, hyperlipidaemia, diabetes mellitus, gestational diabetes mellitus, or prediabetes) and age at first major adverse cardiovascular event (MACE) (cardiovascular death, myocardial infarction, coronary revascularisation, stroke, admission for peripheral vascular disease, and admission for heart failure). Analyses were adjusted for gestational age at entry, sex, and clustering. Of 1,218 infants born to 1,115 mothers, we followed up 424 (46% of survivors; 212 [50%] female) at mean (standard deviation) age 49.3 (1.0) years. There were no differences between those exposed to betamethasone or placebo for cardiovascular risk factors (159/229 [69.4%] versus 131/195 [67.2%]; adjusted relative risk 1.02, 95% confidence interval [CI] [0.89, 1.18;]; p = 0.735) or age at first MACE (adjusted hazard ratio 0.58, 95% CI [0.23, 1.49]; p = 0.261). There were also no differences in the components of these composite outcomes or in any of the other secondary outcomes. Key limitations were follow-up rate and lack of in-person assessments. CONCLUSIONS: There is no evidence that antenatal corticosteroids increase the prevalence of cardiovascular risk factors or incidence of cardiovascular events up to 50 years of age. Established benefits of antenatal corticosteroids are not outweighed by an increase in adult cardiovascular disease.

Comparison of outcomes of the 50-year follow-up of a randomized trial assessed by study questionnaire and by data linkage: The CONCUR study.

BACKGROUND/AIMS: Self-reported questionnaires on health status after randomized trials can be time-consuming, costly, and potentially unreliable. Administrative data sets may provide cost-effective, less biased information, but it is uncertain how administrative and self-reported data compare to identify chronic conditions in a New Zealand cohort. This study aimed to determine whether record linkage could replace self-reported questionnaires to identify chronic conditions that were the outcomes of interest for trial follow-up. METHODS: Participants in 50-year follow-up of a randomized trial were asked to complete a questionnaire and to consent to accessing administrative data. The proportion of participants with diabetes, pre-diabetes, hyperlipidaemia, hypertension, mental health disorders, and asthma was calculated using each data source and agreement between data sources assessed. RESULTS: Participants were aged 49 years (SD = 1, n = 424, 50% male). Agreement between questionnaire and administrative data was slight for pre-diabetes (kappa = 0.10), fair for hyperlipidaemia (kappa = 0.27), substantial for diabetes (kappa = 0.65), and moderate for other conditions (all kappa >0.42). Administrative data alone identified two to three times more cases than the questionnaire for all outcomes except hypertension and mental health disorders, where the questionnaire alone identified one to two times more cases than administrative data. Combining all sources increased case detection for all outcomes. CONCLUSIONS: A combination of questionnaire, pharmaceutical, and laboratory data with expert panel review were required to identify participants with chronic conditions of interest in this follow-up of a clinical trial.

Prevalence and determinants of perinatal mental disorders in women with gestational diabetes in New Zealand: Findings from a national longitudinal study.

INTRODUCTION: Concurrent diagnosis of gestational diabetes mellitus and mental disorders is associated with adverse outcomes for mother and child, but there is limited information about prevalence or which women are at risk. MATERIAL AND METHODS: This study was a prospective cohort study of women with gestational diabetes from 10 hospitals in New Zealand who reported anxiety (6-item Spielberger State-Trait Anxiety Inventory), depression (Edinburgh Postnatal Depression Scale) and health-related quality of life (36-Item Short-Form General Health Survey) at time of gestational diabetes diagnosis (baseline), 36 weeks' gestation, and 6 months postpartum. Potential predictors were assessed using multivariable logistic regression. RESULTS: Among 414 respondents, 17% reported anxiety, 16% vulnerability to depression and 27% poor mental health-related quality of life at time of gestational diabetes diagnosis. At 36 weeks' gestation, prevalence decreased for vulnerability to depression (8%) and poor mental health-related quality of life (20%). Younger maternal age, Pacific ethnicity, previous history of gestational diabetes, and older gestational age at time of gestational diabetes diagnosis were associated with poorer mental health outcomes. At 6 months postpartum the prevalence of mental disorders did not differ from in late pregnancy and they were associated with later gestational age at time of gestational diabetes diagnosis and elevated 2-hour postprandial glucose concentrations. CONCLUSIONS: Perinatal mental disorders are common at time of diagnosis among women with gestational diabetes in New Zealand and had decreased by late pregnancy and at 6 months after birth. These disorders are more common among women with specific risk factors who may therefore benefit from additional support.

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.

Airflow limitation and mortality during cancer screening in the National Lung Screening Trial: why quantifying airflow limitation matters.

IMPORTANCE: Current eligibility criteria for lung cancer (LC) screening are derived from randomised controlled trials and primarily based on age and smoking history. However, the individual benefits of screening are highly variable and potentially attenuated by co-morbidities such as advanced airflow limitation (AL). OBJECTIVE: To examine the relationship between the presence and severity of AL and screening outcomes. METHODS: This was a secondary analysis of 18 463 high-risk smokers, a substudy from the National Lung Screening Trial, who underwent pre-bronchodilator spirometry at baseline and median follow-up of 6.1 years. We used descriptive statistics and a competing risk proportional hazards model to examine differences in screening outcomes by chronic obstructive pulmonary disease severity group. RESULTS: The risk of developing LC increased with worsening AL (effect size=0.34, p<0.0001), as did the risk of dying of LC (effect size=0.35, p<0.0001). While those with severe AL (Global Initiative for Obstructive Lung Disease, GOLD grade 3-4) had the highest risk of LC and the highest LC mortality, they also had fewer adenocarcinomas (effect size=-0.20, p=0.008) and a lower surgery rate (effect size=-0.16, p=0.014) despite comparable staging, and greater non-LC mortality relative to LC mortality (effect size=0.30, p<0.0001). In participants with no AL, screening with CT was associated with a significant reduction in LC deaths relative to chest X-ray (30.3%, 95% CI 4.5% to 49.2%, p<0.05). The clinically relevant but attenuated reduction in those with AL (18.5%, 95% CI -8.4% to 38.7%, p>0.05) could be attributed to GOLD 3-4, where no appreciable mortality reduction was observed. CONCLUSION: Despite a greater risk of LC, severe AL was not associated with any apparent reduction in LC mortality following screening.

Betamethasone for Preterm Birth: Auckland Steroid Trial Full Results and New Insights 50 Years on.

OBJECTIVES: The objective of this study was to use modern analysis and reporting methods to present the full results of the first randomized trial of antenatal corticosteroids, performed 50 years ago. STUDY DESIGN: In this single-center trial, women at risk of preterm birth at 24 to less than 37 weeks of gestation were randomized to receive 2 doses of betamethasone or placebo, 24 hours apart. Women and their caregivers were blinded to treatment allocation. The primary outcome was respiratory distress syndrome. Secondary outcomes included measures of neonatal mortality and morbidity, mode of birth, and maternal infection. RESULTS: Between 1969 and 1974, 1115 women (1142 pregnancies) were randomized, 560 pregnancies (601 infants) to betamethasone and 582 (617 infants) to placebo. The risk of respiratory distress syndrome was significantly reduced in the betamethasone group compared with placebo (8.8% vs 14.4%, adjusted relative risk 0.62, 95% CI 0.45-0.86, P = .004). Subgroup analyses indicated greater efficacy in male than female infants but no effect of tocolytic therapy or doubling of betamethasone dose. Fetal or neonatal death, neonatal or maternal infection, neonatal hypoglycaemia, cesarean delivery, and lactation status at discharge were not different between the groups. CONCLUSIONS: Antenatal betamethasone administered to women at risk of preterm birth between 24 and less than 37 weeks of gestation reduces the incidence of respiratory distress syndrome, with greater effect in male than in female infants. Doubling the dose of betamethasone does not provide additional benefit.

Prophylactic Oral Dextrose Gel and Neurosensory Impairment at 2-Year Follow-up of Participants in the hPOD Randomized Trial.

Importance: Prophylactic oral dextrose gel reduces neonatal hypoglycemia, but later benefits or harms remain unclear. Objective: To assess the effects on later development of prophylactic dextrose gel for infants born at risk of neonatal hypoglycemia. Design, Setting, and Participants: Prospective follow-up of a multicenter randomized clinical trial conducted in 18 Australian and New Zealand hospitals from January 2015 to May 2019. Participants were late preterm or term at-risk infants; those randomized in 9 New Zealand centers (n = 1359) were included and followed up between January 2017 and July 2021. Interventions: Infants were randomized to prophylactic 40% dextrose (n = 681) or placebo (n = 678) gel, 0.5 mL/kg, massaged into the buccal mucosa 1 hour after birth. Main Outcomes and Measures: The primary outcome of this follow-up study was neurosensory impairment at 2 years' corrected age. There were 44 secondary outcomes, including cognitive, language, and motor composite Bayley-III scores (mean [SD], 100 [15]; higher scores indicate better performance). Results: Of eligible infants, 1197 (91%) were assessed (581 females [49%]). Neurosensory impairment was not significantly different between the dextrose and placebo gel groups (20.8% vs 18.7%; unadjusted risk difference [RD], 2.09% [95% CI, -2.43% to 6.60%]; adjusted risk ratio [aRR], 1.13 [95% CI, 0.90 to 1.41]). The risk of cognitive and language delay was not significantly different between the dextrose and placebo groups (cognitive: 7.6% vs 5.3%; RD, 2.32% [95% CI, -0.46% to 5.11%]; aRR, 1.40 [95% CI, 0.91 to 2.17]; language: 17.0% vs 14.7%; RD, 2.35% [95% CI, -1.80% to 6.50%]; aRR, 1.19 [95% CI, 0.92 to 1.54]). However, the dextrose gel group had a significantly higher risk of motor delay (2.5% vs 0.7%; RD, 1.81% [95% CI, 0.40% to 3.23%]; aRR, 3.79 [95% CI, 1.27 to 11.32]) and significantly lower composite scores for cognitive (adjusted mean difference [aMD], -1.30 [95% CI, -2.55 to -0.05]), language (aMD, -2.16 [95% CI, -3.86 to -0.46]), and motor (aMD, -1.40 [95% CI, -2.60 to -0.20]) performance. There were no significant differences between groups in the other 27 secondary outcomes. Conclusions and Relevance: Among late preterm and term infants born at risk of neonatal hypoglycemia, prophylactic oral 40% dextrose gel at 1 hour of age, compared with placebo, resulted in no significant difference in the risk of neurosensory impairment at 2 years' corrected age. However, the study may have been underpowered to detect a small but potentially clinically important increase in risk, and further research including longer-term follow-up is required. Trial Registration: anzctr.org.au Identifier: ACTRN12614001263684.

Chr15q25 genetic variant (rs16969968) independently confers risk of lung cancer, COPD and smoking intensity in a prospective study of high-risk smokers.

IMPORTANCE: While cholinergic receptor nicotinic alpha 5 (CHRNA5) variants have been linked to lung cancer, chronic obstructive pulmonary disease (COPD) and smoking addiction in case-controls studies, their corelationship is not well understood and requires retesting in a cohort study. OBJECTIVE: To re-examine the association between the CHRNA5 variant (rs16969968 AA genotype) and the development of lung cancer, relative to its association with COPD and smoking. METHODS: In 9270 Non-Hispanic white subjects from the National Lung Screening Trial, a substudy of high-risk smokers were followed for an average of 6.4 years. We compared CHRNA5 genotype according to baseline smoking exposure, lung function and COPD status. We also compared the lung cancer incidence rate, and used multiple logistic regression and mediation analysis to examine the role of the AA genotype of the CHRNA5 variant in smoking exposure, COPD and lung cancer. RESULTS: As previously reported, we found the AA high-risk genotype was associated with lower lung function (p=0.005), greater smoking intensity (p<0.001), the presence of COPD (OR 1.28 (95% CI 1.10 to 1.49) p=0.0015) and the development of lung cancer (HR 1.41, (95% CI 1.03 to 1.93) p=0.03). In a mediation analyses, the AA genotype was independently associated with smoking intensity (OR 1.42 (95% CI 1.25 to 1.60, p<0.0001), COPD (OR 1.25, (95% CI 1.66 to 2.53), p=0.0015) and developing lung cancer (OR 1.37, (95% CI 1.03 to 1.82) p=0.03). CONCLUSION: In this large-prospective study, we found the CHRNA5 rs 16 969 968 AA genotype to be independently associated with smoking exposure, COPD and lung cancer (triple whammy effect).

Glucose Profiles in Healthy Term Infants in the First 5 Days: The Glucose in Well Babies (GLOW) Study.

OBJECTIVES: To determine postnatal changes in plasma and interstitial glucose concentrations of healthy infants receiving current recommended care and to compare the incidence of low concentrations with recommended thresholds for treatment of at-risk infants. STUDY DESIGN: A prospective masked observational study in Hamilton, New Zealand. Healthy, term, appropriately grown singletons had continuous glucose monitoring and repeated heel-prick plasma glucose measurements (4 in the first 24 hours then twice daily using the glucose oxidase method) from birth to 120 hours. RESULTS: The 67 infants had a mean birth weight of 3584 ± 349 g, and gestational age of 40.1 ± 1.2 weeks. The mean glucose concentrations increased over the first 18 hours, remained stable to 48 hours (59 ± 11 mg/dL; 3.3 ± 0.6 mmol/L)] before increasing to a new plateau by the fourth day (89 ± 13 mg/dL; 4.6 ± 0.7 mmol/L). Plasma glucose concentrations of 47 mg/dL (2.6 mmol/L) approximated the 10th percentile in the first 48 hours, and 39% of infants had ≥1 episode below this threshold. Early term infants had lower mean glucose concentrations than those born at later gestational ages and were more likely to have episodes <47 mg/dL (<2.6 mmol/L) (19/32 [59%] vs 7/35 [20%]; relative risk, 3.0; 95% CI, 1.4-6.1; P = .001). CONCLUSIONS: Healthy infants seem to complete their metabolic transition by day 4. Many have glucose concentrations below the accepted thresholds for treatment of hypoglycemia. TRIAL REGISTRATION: ACTRN: 12615000986572.

Effects of Neonatal Hyperglycemia on Retinopathy of Prematurity and Visual Outcomes at 7 Years of Age: A Matched Cohort Study.

OBJECTIVE: To determine whether neonatal hyperglycemia is associated with retinopathy of prematurity (ROP), visual outcomes, and ocular growth at 7 years of age. STUDY DESIGN: Children born preterm (<30 weeks of gestational age) at a tertiary hospital in Auckland, New Zealand, who developed neonatal hyperglycemia (2 blood glucose concentrations ≥153 mg/dL [8.5 mmol/L] 4 hours apart) were matched with children who were not hyperglycemic (matching criteria: sex, gestational age, birth weight, age, socioeconomic status, and multiple birth) and assessed at 7 years of corrected age. The primary outcome, favorable overall visual outcome (visual acuity ≤0.3 logarithm of the minimum angle of resolution, no strabismus, stereoacuity ≤240 arcsec, not requiring spectacles) was compared between groups using generalized matching criteria-adjusted linear regression models. RESULTS: Assessments were performed on 57 children with neonatal hyperglycemia (hyperglycemia group) and 54 matched children without hyperglycemia (control group). There were no differences in overall favorable visual outcome (OR 0.95, 95% CI 0.42-2.13, P = .90) or severe ROP incidence (OR 2.20, 95% CI 0.63-7.63, P = .21) between groups. Children with hyperglycemia had poorer binocular distance visual acuity (mean difference 0.08, 95% CI 0.03-0.14 logarithm of the minimum angle of resolution, P < .01), more strabismus (OR 6.22, 95% CI 1.31-29.45, P = .02), and thicker crystalline lens (mean difference 0.14, 95% CI 0.04-0.24 mm, P < .01). Maximum blood glucose concentration was greater in the ROP-treated group compared with the ROP-not treated and no ROP groups after adjusting for sex, gestational age, and birth weight z score (P = .02). CONCLUSIONS: Neonatal hyperglycemia was not associated with overall visual outcomes at 7 years of age. However, there were between-group differences for specific outcome measures relating to interocular lens growth and binocular vision. Further follow-up is required to determine implications on long-term visual outcome.

Relationships Between Early Neonatal Nutrition and Neurodevelopment at School Age in Children Born Very Preterm.

OBJECTIVES: The aim of this study was to determine whether a new nutrition protocol designed to increase early protein intakes while reducing fluid volume in infants born very preterm was associated with altered neurodevelopment and growth in childhood. METHODS: A retrospective, observational cohort study of children born <30 weeks' gestation or <1500 g and admitted to the neonatal unit, National Women's Hospital, Auckland, New Zealand, before and after a change in nutrition protocol. The primary outcome was neurodevelopmental impairment at 7 years (any of Wechsler Intelligence Scale for Children full scale IQ < 85, Movement Assessment Battery for Children-2 total score ≤5th centile, cerebral palsy, blind, or deaf requiring aids). Outcomes were compared between groups and for the overall cohort using generalized linear regression, adjusted for sex and birth weight z score. RESULTS: Of 201 eligible children, 128 (64%) were assessed (55/89 [62%] exposed to the old nutrition protocol, 73 of 112 [65%] to the new protocol). Children who experienced the new protocol received more protein, less energy, and less carbohydrate in postnatal days 1 to 7. Neurodevelopmental impairment was similar at 7 years (30/73 [41%] vs 25/55 [45%], adjusted odds ratio [AOR] [95% confidence interval] 0.78 [0.35-1.70], P = 0.55), as was the incidence of cerebral palsy (AOR 7.36 [0.88-61.40], P = 0.07). Growth and body composition were also similar between groups. An extra 1 g/kg parenteral protein intake in postnatal days 1 to 7 was associated with a 27% increased odds of cerebral palsy (AOR 1.27 [1.03-1.57], P = 0.006). CONCLUSIONS: Higher early protein intakes do not change overall rates of neurodevelopmental impairment or growth at 7 years. Further research is needed to determine the effects of higher early parenteral protein intake on motor development.

Fibroblast growth factor 23 levels decline following sleeve gastrectomy.

OBJECTIVE: Levels of fibroblast growth factor 23 (FGF23) have been positively associated with measures of adiposity, cardiovascular disease and mortality. It is unclear whether the relationship of FGF23 with cardiovascular disease and mortality is confounded by obesity. We aimed to determine whether FGF23 concentrations decline following a reduction in adiposity after sleeve gastrectomy (SG). DESIGN: The effect of SG on FGF23 was evaluated in 22 obese adults (59% male) with type 2 diabetes. Fat mass, weight, BMI, plasma intact FGF23, parathyroid hormone (PTH) and leptin were determined at baseline and at 12 months following SG. RESULTS: At baseline, median (IQR) age was 51 (43-54) years, fat mass 47.8 (41.0-59.4) kg, BMI 40.9 (36.9-46.9) kg/m2 and FGF23 66.2 (55.3-82.9) pg/mL. Significant changes in median BMI (-10.8 kg/m2 , 95% CI: -12.9 to -7.2, P < 0.0001), fat mass (-20.0 kg, 95% CI: -26.7 to -12.4, P < 0.0001) and weight (-34.7 kg, 95% CI -40.0 to -23.1, P < 0.0001) were observed after SG. FGF23 (-12.4 pg/mL, 95% CI: -19.5 to 2.0, P = 0.005), PTH (-1.1 pmol/L, 95% CI: -1.7 to 0.2, P = 0.009) and leptin (-1687 pg/mL, 95% CI -4524 to -563, P = 0.01) declined following SG. Change in FGF23 was not significantly associated with change in measures of adiposity, PTH or leptin. CONCLUSIONS: FGF23 concentrations decline in the setting of significant weight loss following SG, implying that increased FGF23 concentrations are a downstream consequence of obesity, which may confound its association with cardiometabolic dysfunction. Mediators of the relationship between adiposity and FGF23 require further elucidation.

Long-Term Stable Bone Mineral Density in HIV-Infected Men Without Risk Factors for Osteoporosis Treated with Antiretroviral Therapy.

INTRODUCTION: Most prospective studies of bone mineral density (BMD) in HIV-infected cohorts taking antiretroviral therapy (ART) have been of short duration, typically < 3 years. Such studies have reported short-term stable or increasing BMD. We assessed whether this BMD stability persists for > 10 years in middle-aged and older men established on ART. METHODS: A 12-year, prospective, longitudinal study in 44 HIV-infected men treated with ART who had measurements of BMD at the lumbar spine, proximal femur and total body at baseline, 2, 6 and 12 years. RESULTS: At baseline, the mean age of participants was 49 years, the mean duration of HIV infection was 8 years, and the mean duration of ART was 50 months. After 12 years, BMD increased by 6.9% (95% CI 3.4 to 10.3) at the lumbar spine, and remained stable (range of BMD change: - 0.6% to 0.0%) at the total hip, femoral neck and total body. Only two individuals had a decrease of > 10% in BMD at any site during follow-up and both decreases in BMD were explained by co-morbid illnesses. CONCLUSIONS: BMD remained stable over 12 years in middle-aged and older HIV-infected men treated with ART. Monitoring BMD in men established on ART who do not have risk factors for BMD loss is not necessary.

The SIARI Score: A Novel Decision Support Tool Outperforms LRINEC Score in Necrotizing Fasciitis.

BACKGROUND: The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) scoring system was developed to aid the diagnosis of necrotizing fasciitis and guide management [1]. AIM: To validate the LRINEC score and identify clinical predictors to develop a refined diagnostic scoring tool for the diagnosis of necrotizing fasciitis at Middlemore Hospital, New Zealand. METHODS: This was a retrospective case-control study of patients admitted to Middlemore Hospital with necrotizing fasciitis and severe cellulitis between January 2000 and December 2010. The LRINEC scores at admission were evaluated for performance in discriminating between cases of necrotizing fasciitis and severe cellulitis. Cases and controls were randomized into developmental and validation cohorts. Univariate and multivariate logistic regression analysis of demographic, clinical, and laboratory variables for the diagnosis of necrotizing fasciitis was performed. The identified independent predictors were used to develop a new diagnostic scoring tool. RESULTS: The area under the receiver operating characteristic curve (C-statistic) of a LRINEC score ≥6 for the diagnosis of necrotizing fasciitis was 0.679. The newly developed SIARI score [Site other than the lower limb, Immunosuppression, Age < 60 years, Renal impairment (creatinine > 141), and Inflammatory markers (CRP ≥ 150, WCC > 25] demonstrated superior diagnostic ability compared with the LRINEC score in both the developmental (C-statistic: 0.832 vs. 0.691, p < 0.001) and validation cohorts (C-statistic: 0.847 vs. 0.667, p < 0.001). CONCLUSION: The LRINEC score exhibited only modest discriminative performance in this cohort, while the SIARI score is a simplified tool that demonstrates superior diagnostic ability for detecting necrotizing fasciitis. Future external validation studies are required to confirm the trends observed in this study.

Greater insulin response to acute fructose ingestion among Maori and Pacific people compared to European people living in Aotearoa New Zealand.

BACKGROUND: Fructose consumption has been linked with insulin resistance, obesity and diabetes, which are more prevalent in those of Maori or Pacific ethnicity compared to New Zealand European. AIM: To determine whether the acute effects of fructose consumption on serum glucose, insulin, lipids and C-reactive protein differs according to body mass index (BMI) and/or ethnicity. METHODS: Participants of Maori (n = 25), Pacific (n = 26) or New Zealand European (n = 25) ethnicity consumed a 64 g fructose/16 g glucose solution. Changes in lipids, glucose, insulin and C-reactive protein were analysed using mixed models for repeated measures. RESULTS: After adjustment for age and gender, those with higher BMI had a higher glucose (P = 0.0064) and insulin (P = 0.0007) response than those with lower BMI. Those of Maori or Pacific ethnicity had similar glucose levels (P = 0.077) to those of New Zealand European ethnicity but higher insulin responses (P = 0.0005), which remained after additional adjustment for BMI (P = 0.001). Reported sugar-sweetened beverages (SSB) intake was higher among Maori and Pacific than New Zealand European (median 1.0 vs 0.0 SSB/day P = 0.002). CONCLUSION: Even after adjustment for BMI, those of Maori and Pacific ethnicity have a significantly higher insulin response to fructose than New Zealand Europeans. Higher habitual SSB intake may be a contributing factor.

Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study.

Aims: Whether prevalence and mortality of patients with heart failure with preserved or mid-range (40-49%) ejection fraction (HFpEF and HFmREF) are similar to those of heart failure with reduced ejection fraction (HFrEF), as reported in some epidemiologic studies, remains highly controversial. We determined and compared characteristics and outcomes for patients with HFpEF, HFmREF, and HFrEF in a prospective, international, multi-ethnic population. Methods and results: Prospective multi-centre longitudinal study in New Zealand (NZ) and Singapore. Patients with HF were assessed at baseline and followed over 2 years. The primary outcome was death from any cause. Secondary outcome was death and HF hospitalization. Cox proportional hazards models were used to compare outcomes for patients with HFpEF, HFmrEF, and HFrEF. Of 2039 patients enrolled, 28% had HFpEF, 13% HFmrEF, and 59% HFrEF. Compared with HFrEF, patients with HFpEF were older (62 vs. 72 years), more commonly female (17% vs. 48%), and more likely to have a history of hypertension (61% vs. 78%) but less likely to have coronary artery disease (55% vs. 41%). During 2 years of follow-up, 343 (17%) patients died. Adjusting for age, sex, and clinical risk factors, patients with HFpEF had a lower risk of death compared with those with HFrEF (hazard ratio 0.62, 95% confidence interval 0.46-0.85). Plasma (NT-proBNP) was similarly related to mortality in both HFpEF, HFmrEF, and HFrEF independent of the co-variates listed and of ejection fraction. Results were similar for the composite endpoint of death or HF and were consistent between Singapore and NZ. Conclusion: These prospective multinational data showed that the prevalence of HFpEF within the HF population was lower than HFrEF. Death rate was comparable in HFpEF and HFmrEF and lower than in HFrEF. Plasma levels of NT-proBNP were independently and similarly predictive of death in the three HF phenotypes. Trial Registration: Australian New Zealand Clinical Trial Registry (ACTRN12610000374066).

All-Cause Mortality Following an Acute Coronary Syndrome: 12-Year Follow-Up of the Comprehensive 2002 New Zealand Acute Coronary Syndrome Audit.

BACKGROUND: To describe the long-term mortality of a complete national cohort of acute coronary syndrome (ACS) patients enrolled in 2002, to compare this with a national age, sex and Maori ethnicity matched population, and to assess the influence of baseline factors on the 12-year mortality. METHODS: We reviewed 721 patients with a discharge diagnosis of an ACS who were enrolled in the first New Zealand ACS audit group cohort over 14days in May 2002. We matched the cohort to the national mortality database using each patient's unique national identity number. RESULTS: Over a median follow-up of 12.7 years of 721 patients discharged with an ACS, overall mortality was 52%: ST-elevation myocardial infarction (STEMI) (58%), non-ST-elevation myocardial infarction (NSTEMI) (61%) and unstable angina pectoris (UAP) (42%) patients, p<0.0001. In an age-adjusted survival model, males had a 29% increased mortality rate compared to females with a hazard ratio of 1.29 (95% CI 1.04, 1.61, p=0.019). Over 12 years there were 339 (47%) deaths, compared to 284 (39%) deaths observed in the matched population. The standardised mortality ratio for patients admitted with an ACS in New Zealand is 1.3 (95% CI 1.2, 1.5) with eight patients per 100 not surviving to 12 years compared to this matched population. CONCLUSIONS: The high mortality rate in this ACS cohort is a stark reminder of the prognostic implications of a presentation with an ACS. It emphasises the on-going need for optimal management of these patients throughout every stage of their initial treatment and subsequent on-going care.

What Happens to Blood Glucose Concentrations After Oral Treatment for Neonatal Hypoglycemia?

OBJECTIVE: To determine the change in blood glucose concentration after oral treatment of infants with hypoglycemia in the first 48 hours after birth. STUDY DESIGN: We analyzed data from 227 infants with hypoglycemia (blood glucose <46.8 mg/dL, 2.6 mmol/L) born at a tertiary hospital who experienced 295 episodes of hypoglycemia. Blood glucose concentrations were measured (glucose oxidase) within 90 minutes after randomization to dextrose or placebo gel plus feeding with formula, expressed breast milk, or breast feeding. RESULTS: The overall mean increase in blood glucose concentration was 11.7 mg/dL (95% CI 10.4-12.8). The increase was greater after buccal dextrose gel than after placebo gel (+3.0 mg/dL; 95% CI 0.7-5.3; P = .01) and greater after infant formula than after other feedings (+3.8 mg/dL; 95% CI 0.8-6.7; P = .01). The increase in blood glucose concentration was not affected by breast feeding (+2.0 mg/dL; 95% CI -0.3 to 44.2; P = .09) or expressed breast milk (-1.4 mg/dL; 95% CI -3.7 to 0.9; P = .25). However, breast feeding was associated with reduced requirement for repeat gel treatment (OR = 0.52; 95% CI 0.28-0.94; P = .03). CONCLUSIONS: Treatment of infants with hypoglycemia with dextrose gel or formula is associated with increased blood glucose concentration and breast feeding with reduced need for further treatment. Dextrose gel and breast feeding should be considered for first-line oral treatment of infants with hypoglycemia.

Serum phosphate is related to adiposity in healthy adults.

BACKGROUND: Inorganic phosphate is a crucial component of cellular energy metabolism. We have identified an inverse relationship between serum phosphate concentration and fat mass in a cohort of healthy men. This study reports those data and determines whether this association is present in two female populations. METHODS: Cross-sectional data from three independent cohorts, consisting of healthy adult males (Male Cohort, n = 323) and healthy postmenopausal women (Female Cohort 1, n = 185; and Female Cohort 2, n = 1471), are reported. Associations between serum phosphate and weight, body mass index (BMI), fat mass and bone mineral density (BMD) were assessed. In a fourth cohort of postmenopausal women (FGF23 Cohort, n = 20), associations between fibroblast growth factor 23 (FGF23), weight and BMI were assessed. RESULTS: Serum phosphate correlated inversely with weight, BMI and fat mass across all three cohorts (r = -0·13 to -0·31, P < 0·0001-0·02). Associations were diminished after adjustment for PTH, but remained significant. In the FGF23 Cohort, FGF23 was positively correlated with weight (r = 0·60, P = 0·007) and BMI (r = 0·49, P = 0·03). Phosphate was inversely associated with BMD in Female Cohorts 1 and 2 (r = -0·08 to -0·29, P < 0·0001-0·02). This relationship was attenuated, but remained significant at most sites, following adjustment for age, fat mass, renal function and 25-hydroxyvitamin D. CONCLUSIONS: Serum phosphate is inversely associated with measures of adiposity in both women and men, largely independently of PTH. FGF23 might mediate these associations. This relationship may be an unrecognized confounder in some of the correlates of serum phosphate already described.