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Objectives In 2015, the 20-item Tophus Impact Questionnaire (TIQ-20) was developed as a tophus-specific patient-reported outcome measure. The aim of this study was to determine whether TIQ-20 scores change during urate-lowering therapy. Methods We analysed data from a 2-year clinical trial of allopurinol dose escalation using a treat-to-target serum urate approach. For participants with tophaceous gout, the longest diameter of up to three index tophi was measured, using Vernier calipers, and the TIQ-20 was recorded at study visits. Participants at the one site were invited to participate in a dual-energy CT (DECT) substudy. Participants were included in this analysis if they had tophaceous gout and TIQ-20 scores available at baseline, Year 1 and Year 2 (n  = 58, 39 with DECT data). Data were analysed using a mixed-model approach to repeated measures. Results Improvements were observed in all tophus measures over the 2-year period. The mean (s. d.) TIQ-20 scores reduced over 2 years from 3.59 (1.77) to 2.46 (1.73), P  < 0.0001, and the mean (95% CI) TIQ-20 change over the 2 years was –1.13 (–1.54, –0.71). The effect size (Cohen's d) for the change in the sum of the index tophi diameter over 2 years was 0.68, for the DECT urate volume was 0.50, and for the TIQ-20 was 0.71. Conclusion For people with tophaceous gout treated with allopurinol using a treat-to-target serum urate approach, improvements in TIQ-20 occurred, as did improvements in physical and imaging tophus measures. These findings demonstrate that the TIQ-20 is a responsive patient-reported instrument of tophus impact. [ABSTRACT FROM AUTHOR]

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. Anthony G B Walters and colleagues assess cardiovascular outcomes fifty years after antenatal exposure to betamethasone, in long-term follow-up of a randomised double-blind, placebo-controlled trial. Author summary: Why was this study done?: Antenatal corticosteroids (ANC) are given to pregnant persons at risk of preterm birth to reduce the risk of death and breathing difficulty for their offspring. Animal studies have shown later adverse effects of ANC on offspring, particularly on their cardiovascular health in adulthood. There is little robust evidence about long-term effects in humans. This study aimed to provide evidence about the long-term effects of ANC on offspring cardiovascular health in adulthood. What did the researchers do and find?: We assessed participants at 50 years of age who had been exposed to ANC or placebo during the first randomised clinical trial of this treatment. We compared cardiovascular disease and cardiovascular risk factors between those exposed to ANC and placebo in 424 participants (46% of those still alive), using a questionnaire and routinely collected administrative data. We found no differences in cardiovascular outcomes between those exposed to ANC and those who were not. What do these findings mean?: There is no evidence that ANC has adverse effects on the cardiovascular health outcomes of offspring up to 50 years of age. The main limitation was the follow-up rate of less than 50% and the use of health questionnaires and routinely collected data rather than in-person assessments. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

\nIntroduction: We sought to investigate if the availability of cerebral fuels soon after birth in healthy term babies was associated with developmental progress at 3 years of age. Methods: Healthy term babies had plasma glucose, lactate, and beta-hydroxybutyrate concentrations measured over the first 5 days. At 3 years, parents completed Ages and Stages (ASQ-3) questionnaires between December 2018 and August 2022. Developmental progress, analysed using structural equation modelling, was compared between children whose median fuel concentrations were above and below the mean neonatal concentrations of glucose (3.3 mmol/L) and total ATP-equivalents (140 mmol/L) in the first 48 h and over the first 5 days. Results: Sixty-four (96%) families returned completed questionnaires. We found no differences between developmental progress in children who had median neonatal plasma glucose concentrations <3.3 or ≥3.3 mmol/L in the first 48 h (estimated mean difference in ASQ scores −1.0, 95% confidence interval: −5.8, 3.7, p = 0.66) or 120 h (−3.7, −12.0, 4.6, p = 0.39]). There were also no differences for any other measures of cerebral fuels including total ATP above and below the median over 48 and 120 h, any plasma or interstitial glucose concentration <2.6 mmol/L, or cumulative duration of interstitial glucose concentration <2.6 mmol/L. Conclusions: There was no detectable relationship between plasma concentrations of glucose, lactate, and beta-hydroxybutyrate soon after birth in healthy term babies and developmental progress at 3 years of age. In the Glucose in Well babies and their later Neurodevelopment (GLOWiNg) study, we investigated whether the availability of brain fuels in healthy term babies during the first 5 days after birth was associated with their neurodevelopmental progress at 3 years of age. We had measured plasma glucose, lactate, and beta-hydroxybutyrate concentrations when the children were babies, as these are the most common brain fuels. We used the Ages and Stages questionnaire, which is completed by parents, to assess the child’s development in areas including communication, motor skills (fine and gross), and problem solving.We studied 64 families whose babies were part of the Glucose in Well Babies (GLOW) study in New Zealand. Using both structural equation modelling and linear regression, we found that even though many babies experienced episodes of low plasma glucose concentrations, there was no detectable relationship between these episodes and developmental progress at 3 years of age. We explored other factors, including glucose concentrations, total fuels available, and the duration of low glucose episodes, and found no significant associations. Our results suggest that in healthy term babies, episodes of low glucose concentrations in the first days after birth may be part of the normal metabolic transition after birth and may not have long-term implications for neurodevelopment. However, larger studies using different assessment tools are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Aim: Hypoglycaemia is common in neonates born to mothers with gestational diabetes mellitus (GDM). We aimed to determine predictors of hypoglycaemia among neonates of women with GDM and association with short‐term outcomes. Methods: We conducted a secondary cohort analysis of data from a multi‐centre randomised trial (the TARGET trial) conducted across ten maternity hospitals in New Zealand between May 2015 and November 2017. Data were analysed using univariate analysis and multivariable forward stepwise logistic regression. Results: Among 1085 neonates, those born to Asian mothers had reduced odds of hypoglycaemia (OR [95% CI]: 0.54 [0.38, 0.75], p = 0.001), as did those born at higher gestational ages (0.76 [0.68, 0.85], p < 0.001). Neonates born to Pacific mothers had increased odds of hypoglycaemia (OR [95% CI]: 1.57 [1.04, 2.39], p = 0.034). Neonates who experienced hypoglycaemia were more likely to experience neonatal intensive care unit admission (8.3% vs. 2.1%; p ≤ 0.001), hyperbilirubinaemia (8.6% vs. 3.3%; p ≤ 0.001) and receive respiratory support (11.4% vs. 4.8%; p ≤ 0.001) and less likely to be breastfed at discharge (92.4% vs. 96.2%; p = 0.009). Conclusion: Among neonates of women with GDM, maternal ethnicity and gestation at birth are independent predictors of hypoglycaemia, and hypoglycaemia is associated with short‐term comorbidities. Additional surveillance may be appropriate for neonates in these high‐risk groups. [ABSTRACT FROM AUTHOR]

Background: Fructose consumption has been linked with insulin resistance, obesity and diabetes, which are more prevalent in those of Māori 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 Māori (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 Māori 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 Māori 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 Māori and Pacific ethnicity have a significantly higher insulin response to fructose than New Zealand Europeans. Higher habitual SSB intake may be a contributing factor. [ABSTRACT FROM AUTHOR]

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 Māori 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Both the FRAX and Garvan calculators are used to estimate absolute risk of fracture, but they sometimes produce different estimates. We sought to determine which patient characteristics contribute to these discrepancies.Study Design: Ten-year hip fracture risk was estimated for 122 women, using both FRAX and Garvan with bone mineral density (BMD).Main Outcome Measures: Differences in estimates of hip fracture were assessed, both in absolute terms and with respect to a treatment threshold of 3%.Results: Garvan estimates were higher than FRAX estimates across the range of ages and BMDs studied. A history of falls or of multiple fractures increased risk calculated by Garvan 3-6-fold, but did not account for all differences between calculators. Discrepancies around a 3% treatment threshold occurred in 31/122 (25%). Women aged 70-74 years, and women with osteopenia were most likely to have discordant estimates. Most discordant estimates (29/31) had a Garvan estimate ≥ 3% and FRAX <3%. Falls, multiple fractures, ethnicity and a history of parental hip fracture contributed to some discordant estimates.Conclusions: Hip fracture risk estimates are usually higher with Garvan than FRAX, and these differences could impact on treatment decisions in about a quarter of patients. Falls and multiple fractures have a strong influence on Garvan risk estimates, when present. Clinically important discrepancies tend to occur in patients who are at borderline fracture risk. In patients with hip fracture risks near the treatment threshold with one calculator, use of the other calculator should be considered to help guide treatment decisions. [ABSTRACT FROM AUTHOR]

A collection of sets is symmetric-difference-free, respectively symmetric difference-closed, if the symmetric difference of any two sets in the collection lies outside, respectively inside, the collection. Recently Buck and Godbole (Size-maximal symmetric difference-free families of subsets of [ n], Graphs Combin. (to appear), ) investigated such collections and showed, in particular, that the the largest symmetric difference-free collection of subsets of an n-set has cardinality 2. We use group theory to obtain shorter proofs of their results. [ABSTRACT FROM AUTHOR]

Background: Dietary supplement use is increasing despite lack of evidence of benefits, or evidence of harm. Press releases issued by the supplements industry might contribute to this situation by using ‘spin’ (strategies to hype or denigrate findings) to distort the results of clinical studies. We assessed press releases issued in response to publication of clinical studies on dietary supplements. Methods and Findings: We analyzed 47 supplements industry press releases and 91 non-industry press releases and news stories, generated in response to 46 clinical studies of dietary supplements published between 1/1/2005 and 5/31/2013. The primary outcome was ‘spin’ content and direction. We also assessed disposition towards use of dietary supplements, reporting of study information, and dissemination of industry press releases. More supplements industry press releases (100%) contained ‘spin’ than non-industry media documents (55%, P<0.001). Hyping ‘spin’ scores were higher in industry than non-industry media documents for studies reporting benefit of supplements (median ‘spin’ score 3.3, 95% CI 1.0–5.5 vs 0.5, 0–1.0; P<0.001). Denigratory ‘spin’ scores were higher in industry than non-industry media documents for studies reporting no effect (6.0, 5.0–7.0 vs 0, 0–0; P<0.001) or harm (6.0, 5.5–7.5 vs 0, 0–0.5; P<0.001) from a supplement. Industry press releases advocated supplement use in response to >90% of studies that reported no benefit, or harm, of the supplement. Industry press releases less frequently reported study outcomes, sample size, and estimates of effect size than non-industry media documents (all P<0.001), particularly for studies that reported no benefit of supplements. Industry press releases were referenced by 148 news stories on the websites of 6 organizations that inform manufacturers, retailers and consumers of supplements. Conclusions: Dietary supplements industry press releases issued in response to clinical research findings are characterized by ‘spin’ that hypes results that are favourable to supplement use and denigrates results that are not. [ABSTRACT FROM AUTHOR]

Exposure to low levels of nitrate in drinking water may have adverse reproductive effects. We reviewed evidence about the association between nitrate in drinking water and adverse reproductive outcomes published to November 2022. Randomized trials, cohort or case–control studies published in English that reported the relationship between nitrate intake from drinking water and the risk of perinatal outcomes were included. Random-effect models were used to pool data. Three cohort studies showed nitrate in drinking water is associated with an increased risk of preterm birth (odds ratio for 1 mg/L NO3-N increased (OR1) = 1.01, 95% CI 1.00, 1.01, I2 = 23.9%, 5,014,487 participants; comparing the highest versus the lowest nitrate exposure groups pooled OR (ORp) = 1.05, 95% CI 1.01, 1.10, I2 = 0%, 4,152,348 participants). Case–control studies showed nitrate in drinking water may be associated with the increased risk of neural tube defects OR1 = 1.06, 95% CI 1.02, 1.10; 2 studies, 2196 participants; I2 = 0%; and ORp = 1.51, 95% CI 1.12, 2.05; 3 studies, 1501 participants; I2 = 0%). The evidence for an association between nitrate in drinking water and risk of small for gestational age infants, any birth defects, or any congenital heart defects was inconsistent. Increased nitrate in drinking water may be associated with an increased risk of preterm birth and some specific congenital anomalies. These findings warrant regular review as new evidence becomes available. [ABSTRACT FROM AUTHOR]

Elevated serum urate is the most important causal risk factor for developing gout. However, in longitudinal cohort studies, a small proportion of people with normal urate levels develop gout and the majority of those with high urate levels do not. These observations may be due to subsequent variations in serum urate over time. Our analysis examined whether single or repeat testing of serum urate more accurately predicts incident gout over time. Individual participant data from three publicly-available cohorts were included. Data from paired serum urate measures 3–5 years apart, followed by an assessment of gout incidence 5–6 years from the second urate measure were used to calculate the predictive ability of four measures of serum urate on incident gout: the first measure, the second measure, the average of the two measures, and the highest of the two measures. Participants with prevalent gout prior to the second measure were excluded. Receiver operator characteristic (ROC) curves and area under the curve (AUC) statistics were computed to compare the four measures. A total of 16,017 participants were included across the three cohorts, with a mean follow-up from the first serum urate test of 9.3 years (range 8.9–10.1 years). Overall, there was a small increase in the mean serum urate between the first and second measures (322 μmol/L (5.42 mg/dL) vs. 340 μmol/L (5.71 mg/dL), P<0.001) which were a mean of 3.5 years apart, but the first and second measures were highly correlated (r = 0.81, P<0.001). No differences were observed in the predictive ability of incident gout between the four measures of serum urate measurement with ROC curve AUC statistics ranging between 0.81 (95% confidence intervals: 0.78–0.84) and 0.84 (95% confidence intervals: 0.81–0.87). These data show that repeat serum urate testing is not superior to a single measure of serum urate for prediction of incident gout over approximately one decade. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Nutritional intake can promote early neonatal brain development in very preterm born neonates (< 32 weeks' gestation). In a group of 7-year-old very preterm born children followed since birth, we examined whether early nutrient intake in the first weeks of life would be associated with long-term brain function and neurocognitive skills at school age. Children underwent resting-state functional MRI (fMRI), intelligence testing (Wechsler Intelligence Scale for Children, 5th Ed) and visual-motor processing (Beery-Buktenica, 5th Ed) at 7 years. Relationships were assessed between neonatal macronutrient intakes, functional connectivity strength between thalamic and default mode networks (DMN), and neuro-cognitive function using multivariable regression. Greater functional connectivity strength between thalamic networks and DMN was associated with greater intake of protein in the first week (β = 0.17; 95% CI 0.11, 0.23, p < 0.001) but lower intakes of fat (β = − 0.06; 95% CI − 0.09, − 0.02, p = 0.001) and carbohydrates (β = − 0.03; 95% CI − 0.04, − 0.01, p = 0.003). Connectivity strength was also associated with protein intake during the first month (β = 0.22; 95% CI 0.06, 0.37, p = 0.006). Importantly, greater thalamic-DMN connectivity strength was associated with higher processing speed indices (β = 26.9; 95% CI 4.21, 49.49, p = 0.02) and visual processing scores (β = 9.03; 95% CI 2.27, 15.79, p = 0.009). Optimizing early protein intake may contribute to promoting long-term brain health in preterm-born children. [ABSTRACT FROM AUTHOR]

Authorship transgressions, duplicate data reporting and reporting/data errors compromise the integrity of biomedical publications. Using a standardized template, we raised concerns with journals about each of these characteristics in 33 pairs of publications originating from 15 preclinical (animal) trials reported by a group of researchers. The outcomes of interest were journal responses, including time to acknowledgement of concerns, time to decision, content of decision letter, and disposition of publications at 1 year. Authorship transgressions affected 27/36 (75%) publications. The median proportion of duplicate data within pairs of publications was 45% (interquartile range 29–57). Data/reporting discrepancies [median 3 (1–5)] were present in 28/33 (85%) pairs. Journals acknowledged receipt of concerns for 53% and 94% of publications by 1 month and 9 months, respectively. After 1 year, journals had communicated decisions for 16/36 (44%) publications. None of the decision letters specifically addressed each of the concerns raised. Decisions were no action, correction and retraction for 9, 3 and 4 publications, respectively: the amounts of duplicate data reporting and data/reporting discrepancies were similar irrespective of journal decision. Authorship transgressions affected 6/9 (67%) publications for which no action was decided. Journal responses to concerns about duplicate publication, authorship transgressions, and data/reporting discrepancies were slow, opaque and inconsistent. [ABSTRACT FROM AUTHOR]

Objective: To examine whether urate‐associated genetic variants differ in their influence on gout risk according to body mass index (BMI). Methods: This research was conducted using the UK Biobank Resource (n = 358,728). Participants were divided into 3 groups: BMI <25 kg/m2 (low/normal), BMI ≥25 kg/m2–<30 kg/m2 (overweight), and BMI ≥30 kg/m2 (obese). Gene–BMI interactions for gout association were tested by logistic regression using a urate genetic risk score (GRS). Results: Compared to participants with a GRS less than the mean, the prevalence of gout was higher in those with a GRS greater than or equal to the mean in the low/normal BMI group (0.27% versus 0.77%), in the overweight BMI group (1.02% versus 3.02%), and in the obese BMI group (2.49% versus 6.23%). A GRS greater than or equal to the mean was positively associated with gout compared to a GRS less than the mean in the low/normal BMI group (odds ratio [OR] 2.89 [95% confidence interval (95% CI) 2.42–3.47]), in the overweight BMI group (OR 3.09 [95% CI 2.84–3.36]), and in the obese BMI group (OR 2.65 [95% CI 2.46–2.86]). There was a mildly attenuated effect of the GRS on gout risk in the obese BMI group compared to the overweight BMI group, but no difference in the effect of the GRS between the low/normal BMI and overweight BMI groups, nor between the low/normal BMI and obese BMI groups. Conclusion: The association of a urate GRS with gout is mildly attenuated in obese individuals compared to overweight individuals. However, genetic variants have a strong effect on gout risk in those with overweight and obese BMIs, with an effect similar to that observed in low/normal BMI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Transcatheter aortic valve implantation (TAVI) is considered for severe aortic valve disease at high and now intermediate risk for surgical aortic valve replacement. Risk stratification plays a critical role decision-making for intervention and modality. We compared the prognostic utility of surgical risk scores for TAVI in this meta-analysis. Methods MEDLINE, Embase, Cochrane and Web of Science databases from 1 January 1980 to 31 December 2015 were searched. Studies were systematically reviewed for inclusion, and data extracted for pooled analyses. Results Amongst 1688 articles searched, 47 full-text articles were screened and 24 studies (12,346 TAVI cases) included for analyses. Pooled c-statistics (95% confidence interval) for operative mortality were EuroSCORE 0.62 (0.57–0.67), EuroSCORE II 0.62 (0.59–0.66), STS Score 0.62 (0.59–0.65). Pooled calibration odds ratios (95%CI) were EuroSCORE 0.31 (0.25–0.38), EuroSCORE II 1.26 (1.06–1.51), STS 0.95 (0.72–1.27). C-statistics (95%CI) for 1-year mortality were EuroSCORE 0.62 (0.57–0.67), EuroSCORE II 0.66 (0.61–0.71) and STS Score 0.58 (0.53–0.64). Conclusion Surgical risk scores at most modestly discriminated operative and 1-year mortality. The EuroSCORE grossly over-estimated operative mortality while the EuroSCORE II and STS Scores fitted better to TAVI outcomes with their own limitations. There is a need for the development and validation of TAVI-specific risk models. [ABSTRACT FROM AUTHOR]

Background: There is wide variation in the use of radial over femoral access for patients with ACS. This study evaluates the factors associated with the selection of radial versus femoral angiography in Australia and New Zealand and the effect of access site on clinical events in acute coronary syndrome (ACS) patients.Methods: An analysis of the SNAPSHOT ACS audit was conducted during May 2012 across 286 hospitals in Australia and New Zealand. Data collected included baseline patient characteristics, hospital site details, treatment received, clinical events in-hospital and mortality at 18 months. Univariate and multivariable analyses were performed.Results: Of the 1621 patients undergoing coronary angiography, access was through the femoral artery in 1043 (63%), and the radial in 578 (36%) patients. Radial access dominated in New Zealand (241 out of 327, 73.7%), compared to Australia (337 out of 1293, 26.1%, p=<0.001), with interstate variation (6% to 54%, p=<0.001). Independent predictors of access site included country of admission (Odds of radial, Aus v NZ OR 0.14, 95% CI 0.08-0.24, p=<0.0001), prior CABG surgery (OR 0.16, 95% CI 0.09-0.31, p=<0.0001), high GRACE score (90th decile) (OR 0.44, 95% CI 0.21-0.91, p=0.026) and admission to a centre with high annual PCI volume (>209 cases per year) (OR 1.86, 95% CI 1.06-3.26, p=0.03). After adjustment, there was no difference in clinical events in-hospital or mortality at 18 months CONCLUSION: Coronary angiography in New Zealand rather than Australia is the strongest predictor of radial access in ACS patients. There was no difference in outcomes according to access site in this population based cohort study. [ABSTRACT FROM AUTHOR]

Background: Risk stratification for mitral valve repair or replacement (MVR) is important in the decision-making for treating several mitral valve disease but is rarely studied. We compared the prognostic utility of EuroSCORE, EuroSCORE II, and Society of Thoracic Surgeons (STS) Score for MVR.Methods: The three scores were retrospectively calculated for consecutive patients undergoing isolated MVR at Auckland City Hospital during 2005-2012 and their discrimination and calibration for mortality and morbidities assessed.Results: There were 408 patients (mitral valve repair 48.1% and replacement 51.9%) followed-up for 6.0 ± 2.6 years. The operative mortality was 2.5%. Mean EuroSCORE, EuroSCORE II, and STS Score were 7.6%, 3.4%, and 3.5%. C-statistics were 0.844, 0.817, and 0.850 for operative mortality. Hosmer-Lemeshow test p values were 0.076, 0.541, and 0.306, and Brier scores 0.0246, 0.0035, and 0.0075, respectively, for operative mortality. The numerically highest c-statistic for predicting complications include EuroSCORE for return to the operating room (c = 0.673); EuroSCORE II for stroke (c = 0.669) and mediastinitis (c = 0.801); and STS for renal failure (c = 0.828), ventilation >24 hours (c = 0.789), and composite morbidity (c = 0.732). The individual STS complication models for MVR had a numerically higher c-statistic only for stroke (c = 0.737).Conclusions: All scores discriminated mortality and most morbidities after MVR, although EuroSCORE over-estimated operative mortality. The STS Score was the best overall predictor of mortality and morbidity in the MVR cohort. [ABSTRACT FROM AUTHOR]

Background: Publication of clinical research findings in prominent journals influences health beliefs and medical practice, in part by engendering news coverage. Randomized controlled trials (RCTs) should be most influential in guiding clinical practice. We determined whether study design of clinical research published in high-impact journals influences media coverage. Methods and Findings: We compared the incidence and amount of media coverage of RCTs with that of observational studies published in the top 7 medical journals between 1 January 2013 and 31 March 2013. We specifically assessed media coverage of the most rigorous RCTs, those with >1000 participants that reported ‘hard’ outcomes. There was no difference between RCTs and observational studies in coverage by major newspapers or news agencies, or in total number of news stories generated (all P>0.63). Large RCTs reporting ‘hard’ outcomes did not generate more news coverage than small RCTs that reported surrogate outcomes and observational studies (all P>0.32). RCTs were more likely than observational studies to attract a journal editorial (70% vs 46%, P = 0.003), but less likely to be the subject of a journal press release (17% vs 50%, P<0.001). Large RCTs that reported ‘hard’ outcomes did not attract an editorial more frequently than other studies (61% vs 58%, P>0.99), nor were they more likely to be the subject of a journal press release (14% vs 38%, P = 0.14). Conclusions: The design of clinical studies whose results are published in high-impact medical journals is not associated with the likelihood or amount of ensuing news coverage. [ABSTRACT FROM AUTHOR]

Background: Observational studies (OS) and randomized controlled trials (RCTs) often report discordant results. In the Women’s Health Initiative Calcium and Vitamin D (WHI CaD) RCT, women were randomly assigned to CaD or placebo, but were permitted to use personal calcium and vitamin D supplements, creating a unique opportunity to compare results from randomized and observational analyses within the same study. Methods: WHI CaD was a 7-year RCT of 1g calcium/400IU vitamin D daily in 36,282 post-menopausal women. We assessed the effects of CaD on cardiovascular events, death, cancer and fracture in a randomized design- comparing CaD with placebo in 43% of women not using personal calcium or vitamin D supplements- and in a observational design- comparing women in the placebo group (44%) using personal calcium and vitamin D supplements with non-users. Incidence was assessed using Cox proportional hazards models, and results from the two study designs deemed concordant if the absolute difference in hazard ratios was ≤0.15. We also compared results from WHI CaD to those from the WHI Observational Study(WHI OS), which used similar methodology for analyses and recruited from the same population. Results: In WHI CaD, for myocardial infarction and stroke, results of unadjusted and 6/8 covariate-controlled observational analyses (age-adjusted, multivariate-adjusted, propensity-adjusted, propensity-matched) were not concordant with the randomized design results. For death, hip and total fracture, colorectal and total cancer, unadjusted and covariate-controlled observational results were concordant with randomized results. For breast cancer, unadjusted and age-adjusted observational results were concordant with randomized results, but only 1/3 other covariate-controlled observational results were concordant with randomized results. Multivariate-adjusted results from WHI OS were concordant with randomized WHI CaD results for only 4/8 endpoints. Conclusions: Results of randomized analyses in WHI CaD were concordant with observational analyses for 5/8 endpoints in WHI CaD and 4/8 endpoints in WHI OS. [ABSTRACT FROM AUTHOR]

Children born very preterm can demonstrate social-cognitive impairments, which may result from limbic system dysfunction. Altered development of the subnuclei of the amygdala, stress-sensitive regions involved in emotional processing, may be key predictors of social-skill development. In a prospective cohort study, 7-year-old children born very preterm underwent neurodevelopmental testing and brain MRI. The Child Behavioral Checklist was used to assess social–emotional outcomes. Subnuclei volumes were extracted automatically from structural scans (n  = 69) and functional connectivity (n  = 66) was examined. General Linear Models were employed to examine the relationships between amygdala subnuclei volumes and functional connectivity values and social–emotional outcomes. Sex was a significant predictor of all social–emotional outcomes (P  < 0.05), with boys having poorer social–emotional outcomes. Smaller right basal nuclei volumes (B  = -0.043, P  = 0.014), smaller right cortical volumes (B  = -0.242, P  = 0.02) and larger right central nuclei volumes (B  = 0.85, P  = 0.049) were associated with increased social problems. Decreased connectivity strength between thalamic and amygdala networks and smaller right basal volumes were significant predictors of greater social problems (both, P  < 0.05), effects which were stronger in girls (P  = 0.025). Dysregulated maturation of the amygdala subnuclei, along with altered connectivity strength in stress-sensitive regions, may reflect stress-induced dysfunction and can be predictive of social–emotional outcomes. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a therapeutic approach of intensive serum urate lowering results in improved bone erosion scores in patients with erosive gout. Methods: We undertook a 2‐year, double‐blind randomized controlled trial of 104 participants with erosive gout who were receiving serum urate–lowering therapy orally and who had serum urate levels of ≥0.30 mmoles/liter at baseline. Participants were randomly assigned to either an intensive serum urate target of <0.20 mmoles/liter or a standard target of <0.30 mmoles/liter (considered the standard according to rheumatology guidelines). Oral serum urate–lowering therapy was titrated to target using a standardized protocol (with the maximum approved doses of allopurinol, probenecid, febuxostat, and benzbromarone). The primary end point was the total computed tomography (CT) bone erosion score. Outcome Measures in Rheumatology (OMERACT) gout core outcome domains were secondary end points. Results: Although the serum urate levels were significantly lower in the intensive target group compared to the standard target group over the study period (P = 0.002), fewer participants in the intensive target group achieved the randomized serum urate target level by year 2 (62% versus 83% of patients in the standard target group; P < 0.05). The intensive target group required higher doses of allopurinol (mean ± SD 746 ± 210 mg/day versus 497 ± 186 mg/day; P < 0.001) and received more combination therapy (P = 0.0004) compared to the standard target group. We observed small increases in CT bone erosion scores in both serum urate target groups over 2 years, with no between‐group difference (P = 0.20). OMERACT core outcome domains (gout flares, tophi, pain, patient's global assessment of disease activity, health‐related quality of life, and activity limitation) improved in both groups over 2 years, with no between‐group differences. Adverse event and serious adverse event rates were similar between the groups. Conclusion: Compared to a serum urate target of <0.30 mmoles/liter, more intensive serum urate lowering is difficult to achieve with an oral urate‐lowering therapy. Intensive serum urate lowering leads to a high medication burden and does not improve bone erosion scores in patients with erosive gout. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: To examine the contributions of specific neurocognitive skills to behaviour problems in children born very preterm. Methods: We assessed children born <30 weeks' gestation or <1500 g at age 7 years using subtests of the Wechsler Intelligence Scale for Children Fourth Edition, performance and questionnaire‐based measures of executive function, and Child Behavior Checklist and Teacher Rating Form. We evaluated the contributions of IQ and executive function to behaviour problems and the moderating effect of sex using multiple regression. Results: The 129 children (mean age = 7.2 years) had lower IQ, inferior executive function and increased internalising problems compared with normative samples. Verbal comprehension skills and working memory were associated with total, internalising and externalising problems at school. Performance‐based and questionnaire‐based executive function were associated with total and externalising behaviour problems both at home and school. Sex moderated the relationships between information processing and parent‐reported total problems, and between teacher‐rated executive function and total problems. Conclusion: Both IQ and executive function are related to behaviour problems in children born very preterm, but the relationships are different in boys and girls. Executive function may be a useful target for intervention. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to examine whether serum urate-associated genetic variants are associated with early-onset gout. Methods Participants with gout in the Genetics of Gout in Aotearoa study with available genotyping were included (n  = 1648). Early-onset gout was defined as the first presentation of gout <40 years of age. Single nucleotide polymorphisms (SNPs) for the 10 loci most strongly associated with serum urate were genotyped. Allelic association of the SNPs with early-onset gout was tested using logistic regression in an unadjusted model and in a model adjusted for sex, body mass index, tophus presence, flare frequency, serum creatinine and highest serum urate. The analysis was also done in two replication cohorts: Eurogout (n  = 704) and Ardea (n  = 755), and data were meta-analysed. Results In the Genetics of Gout in Aotearoa study, there were 638 (42.4%) participants with early-onset gout. The ABCG2 rs2231142 gout risk T-allele was present more frequently in participants with early-onset gout compared with the later-onset group. For the other SNPs tested, no differences in risk allele number were observed. In the allelic association analysis, the ABCG2 rs2231142 T-allele was associated with early-onset gout in unadjusted and adjusted models. Analysis of the replication cohorts confirmed the association of early-onset gout with the ABCG2 rs2231142 T-allele, but not with other serum urate-associated SNPs. In the meta-analysis, the odds ratio (95% CI) for early-onset gout for the ABCG2 rs2231142 T-allele was 1.60 (1.41, 1.83). Conclusion In contrast to other serum urate-raising variants, the ABCG2 rs2231142 T-allele is strongly associated with early-onset gout. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: We investigated whether responses about possible scientific misconduct from journals to journalists would differ in speed, usefulness, and tone from responses to academics. Twelve journals that published 23 clinical trials about which concerns had been previously raised were randomly assigned to enquiries by a journalist or academics. Emails were sent every 3 weeks to the journal editor. We recorded the time for the journal to respond, and two investigators independently assessed the usefulness and tone of the journal responses. Results: 10/12 journals responded: 3 after one email, 5 after two emails, and 2 after three emails (median time from first email to response: 21 days; no difference in response times to journalist or academics, P = 0.25). Of the 10 responses, 8 indicated the journal was investigating, 5 had a positive tone, 4 a neutral tone, and 1 a negative tone. Five of the enquiries by the academics produced information of limited use and 1 no useful information, whereas none of the 6 journalist enquiries produced useful information (P = 0.015). None of the 10 responses was considered very useful. In conclusion, journal responses to a journalist were less useful than those to academics in understanding the status or outcomes of journal investigations. [ABSTRACT FROM AUTHOR]

Objective. Effective translation of evidence to practice may depend on systems of care characteristics within the health service. The present study evaluated associations between hospital expertise and infrastructure capacity and acute coronary syndrome (ACS) care as part of the SNAPSHOT ACS registry. Methods. A survey collected hospital systems and process data and our analysis developed a score to assess hospital infrastructure and expertise capacity. Patient-level data from a registry of 4387 suspected ACS patients enrolled over a 2-wee Results. Of 375 participating hospitals, 348 (92.8%) were included in the analysis. Higher expertise was associated with increased coronary angiograms (440/1329; 33.1%), 580/1656 (35.0%) and 609/1402 (43.4%) for low, intermediate and high expertise capacity respectively; P < 0.001) and the prescription of guideline therapies observed a tendency for an association with (531/1329 (40.0%), 733/1656 (44.3%) and 603/1402 (43.0%) for low, intermediate and high expertise capacity respectively; P = 0.056), but not rehabilitation (474/1329 (35.7%), 603/1656 (36.4%) and 535/1402 (38.2%) for low, intermediate and high expertise capacity respectively; P = 0.377). Higher expertise capacity was associated with a lower incidence of major adverse events (152/1329 (11.4%), 142/1656 (8.6%) and 149/149 (10.6%) for low, intermediate and high expertise capacity respectively; P = 0.026), as well as adjusted mortality within 18 months (low vs intermediate expertise capacity: odds ratio (OR) 0.79, 95% confidence interval (CI) 0.58-1.08, P = 0.153; intermediate vs high expertise capacity: OR 0.64, 95% CI 0.48-0.86, P = 0.003). Conclusions. Both higher-level expertise in decision making and infrastructure capacity are associated with improved evidence translation and survival over 18 months of an ACS event and have clear healthcare design and policy implications. [ABSTRACT FROM AUTHOR]

The article discusses microbiological profile of pseudomonas aeruginosa keratitis with international reports of growing antibiotic resistance. Topics discussed include retrospective analysis for treatment of bacterial keratitis, multivariate analysis depicting shorter healing time for ciprofloxacin monotherapy and finding results of fortified combination antibiotics and fluoroquinolone monotherapy.

Background: Intravenous zoledronate 5 mg annually reduces fracture risk, and 5 mg every 2 years prevents bone loss, but the optimal dosing regimens for these indications are uncertain.Methods: We conducted a 3-year open-label extension of a 2-year randomized, placebo-controlled, double-blind study. Late postmenopausal women with osteopenia were assigned to receive a single baseline dose of 1 mg, 2.5 mg or 5 mg of zoledronate or placebo. The primary outcome was change in spine bone mineral density (BMD). Secondary outcomes were changes in hip BMD and serum markers of bone turnover.Results: The study involved 160 women. Zoledronate increased BMD and reduced markers of bone turnover in a dose-dependent manner. After 2 years, the 1-mg, 2.5-mg and 5-mg zoledronate doses increased spine BMD over placebo by 5.0% (95% confidence interval [CI] 3.0% to 7.0%), 5.7% (95% CI 3.7% to 7.7%) and 5.7% (95% CI 3.7% to 7.6%), respectively; after 5 years, the respective increases were 2.0% (95% CI -1.1% to 5.0%), 2.2% (95% CI -1.0% to 5.4%) and 5.1% (95% CI 2.2% to 8.1%). After 2 years, the 1-mg, 2.5-mg and 5-mg zoledronate doses increased total hip BMD over placebo by 2.6% (95% CI 1.3% to 3.9%), 4.1% (95% CI 2.9% to 5.4%) and 4.7% (95% CI 3.4% to 5.9%), respectively; after 5 years, the respective increases were 1.8% (95% CI -0.1% to 3.8%), 2.8% (95% CI 0.8% to 4.8%) and 5.4% (95% CI 3.5% to 7.3%). BMD remained above baseline values for 2-3 years in the 1-mg group, 3-4 years in the 2.5-mg group and at least 5 years in the 5-mg group.Interpretation: The antiresorptive activity of single zoledronate doses of 1-5 mg persist for at least 3 years in postmenopausal women with osteopenia. Clinical trials would be justified to evaluate the effects on fracture risk of less frequent or lower doses of zoledronate than are currently recommended.Trial Registration: www.anzctr.org.au, no. ACTRN12607000576426. [ABSTRACT FROM AUTHOR]

Aim: To investigate the relationship between heart rate and survival in patients with heart failure (HF) and coexisting atrial fibrillation (AF).Methods and Results: Patients with AF included in the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) meta-analysis were the main focus of this analysis (3259 patients from 17 studies). The outcome was all-cause mortality at 3 years. Heart rate was analysed as a categorical (tertiles; T1 ≤77 b.p.m., T2 78-98 b.p.m., T3 ≥98 b.p.m.) and continuous variable. Cox proportional hazard models were used to compare the risk of all-cause death between tertiles of baseline heart rate. Patients in the highest tertile were more often female, less likely to have an ischaemic aetiology or diabetes, had a lower ejection fraction but higher blood pressure and New York Heart Association (NYHA) class. Higher heart rate was associated with higher mortality in patients with sinus rhythm (SR) but not in those in AF. In patients with heart failure and reduced ejection fraction (HF-REF) and AF, death rates per 100 patient years were lowest in the highest heart rate tertile (T1 18.9 vs. T3 15.9) but this difference was not statistically significant (P = 0.10). In patients with heart failure and preserved ejection fraction (HF-PEF), death rates per 100 patient years were highest in the highest heart rate tertile (T1 14.6 vs. T3 16.0, P = 0.014). However, after adjustment for other important prognostic variables, higher heart rate was no longer associated with higher mortality in HF-PEF (or HF-REF).Conclusions: In this meta-analysis of patients with HF, heart rate does not have the same prognostic significance in patients in AF as it does in those in SR, irrespective of ejection fraction or treatment with beta-blocker. [ABSTRACT FROM AUTHOR]

Background Risk models play an important role in stratification of patients for cardiac surgery, but their prognostic utilities for post-operative complications are rarely studied. We compared the EuroSCORE, EuroSCORE II, Society of Thoracic Surgeon's (STS) Score and an Australasian model (Aus-AVR Score) for predicting morbidities after aortic valve replacement (AVR), and also evaluated seven STS complications models in this context. Methods We retrospectively calculated risk scores for 620 consecutive patients undergoing isolated AVR at Auckland City Hospital during 2005-2012, assessing their discrimination and calibration for post-operative complications. Results Amongst mortality scores, the EuroSCORE was the best at discriminating stroke (c-statistic 0.845); the EuroSCORE II at deep sternal wound infection (c=0.748); and the STS Score at composite morbidity or mortality (c=0.666), renal failure (c=0.634), ventilation>24 hours (c=0.732), return to theatre (c=0.577) and prolonged hospital stay >14 days post-operatively (c=0.707). The individual STS complications models had a marginally higher c-statistic (c=0.634-0.846) for all complications except mediastinitis, and had good calibration (Hosmer-Lemeshow test P-value 0.123-0.915) for all complications. Conclusion The STS Score was best overall at discriminating post-operative complications and their composite for AVR . All STS complications models except for deep sternal wound infection had good discrimination and calibration for post-operative complications. [ABSTRACT FROM AUTHOR]

Decision making regarding surgery for acute bacterial endocarditis is complex given its heterogeneity and often fatal course. Few studies have investigated the utility of operative risk scores in this setting. Endocarditis-specific scores have recently been developed. We assessed the prognostic utility of contemporary risk scores for mortality and morbidity after endocarditis surgery. Additive and logistic EuroSCORE I, EuroSCORE II, additive Society of Thoracic Surgeon's (STS) Endocarditis Score and additive De Feo-Cotrufo Score were retrospectively calculated for patients undergoing surgery for endocarditis during 2005-2011. Pre-specified primary outcomes were operative mortality, composite morbidity and mortality during follow-up. A total of 146 patients were included with an operative mortality of 6.8 % followed for 4.1 ± 2.4 years. Mean scores were additive EuroSCORE I: 8.0 ± 2.5, logistic EuroSCORE I: 13.2 ± 10.1 %, EuroSCORE II: 9.1 % ± 9.4 %, STS Score: 32.2 ± 13.5 and De Feo-Cotrufo Score: 14.6 ± 9.2. Corresponding areas under curve (AUC) for operative mortality 0.653, 0.645, 0.656, 0.699 and 0.744; for composite morbidity were 0.623, 0.625, 0.720, 0.714 and 0.774; and long-term mortality 0.588, 0.579, 0.686, 0.735 and 0.751. The best tool for post-operative stroke was EuroSCORE II: AUC 0.837; for ventilation >24 h and return to theatre the De Feo-Cotrufo Scores were: AUC 0.821 and 0.712. Pre-operative inotrope or intra-aortic balloon pump treatment, previous coronary bypass grafting and dialysis were independent predictors of operative and long-term mortality. In conclusion, risk models developed specifically from endocarditis surgeries and incorporating endocarditis variables have improved prognostic ability of outcomes, and can play an important role in the decision making towards surgery for endocarditis. [ABSTRACT FROM AUTHOR]

Aims Primary percutaneous coronary intervention (PCI) is the optimal management for ST segment elevation myocardial infarction (STEMI) patients. We reviewed the largest primary PCI regional service in New Zealand: the Auckland/Northland service based at Auckland City Hospital, to assess patient management, in particular the door to reperfusion times (DTRTs), and predictors of death in hospital. Methods We obtained patient details from a comprehensive prospective database of all primary PCI patients admitted with STEMI from 1/1/12 to 31/12/12 to the Auckland City Hospital cardiac catheterisation laboratory. Of four District Health Boards (DHBs) within the region, two accessed this regional service at all times, and two accessed the Auckland City Hospital cardiac catheterisation laboratory ‘after hours’: all times except for 08:00 to 16:00 hours on Monday to Friday. Results A total of 401 adult patients underwent a primary PCI at the Auckland City Hospital Regional centre for a STEMI presentation, over the 12 months period. The median patient age was 61 years, 77% were male. Overall 183 (46%) (95% CI 41, 51) patients achieved a DTRT of < 90 mins, and 266 (66%) (95% CI 61, 71) a DTRT of < 120mins, with a clear geographical influence to these times. Of 27 patients with direct transfer to the catheter laboratory from the community, the DTRT was < 120 mins in 24 (92%) (95% CI 72, 96) patients. In-hospital mortality was 24 (6%) patients (95% CI 4, 9). Conclusions The 2012 Auckland/Northland primary PCI service delivers good outcomes consistent with current Australasian standards. Although geographical isolation complicates door to reperfusion times, these may potentially be improved by more focus on direct transfer to the cardiac catheterisation laboratory, especially directly from the community. [ABSTRACT FROM AUTHOR]

Background: Children born very preterm are at higher risk of adverse neurocognitive and educational outcomes. However, how low intelligence (IQ) and low executive function may each contribute to poorer academic outcomes at school age requires clarification.Aim: To examine the associations between intelligence, executive function and academic achievement in children born very preterm.Design/methods: This cohort study assessed children born <30 weeks' gestation or <1500 g at age 7 years using the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) for IQ, and the Test of Everyday Attention for Children (TEA-Ch) and Behavior Rating Inventory of Executive Function (BRIEF) for executive function. Academic achievement was rated by teachers against curriculum standards.Results: Of the 76 children (35 girls, 41 boys, mean age = 7.2 year), 22 (28%) were rated below expected level for reading, 32 (42%) for writing and 38 (50%) for mathematics. After adjustment for sex and socioeconomic status, low IQ (OR's 9.0-12.3) and most low executive function measures (OR's 4.1-9.3) were associated with below-expected achievement. After further adjustment for IQ, low cognitive flexibility (OR = 9.3, 95% CI = 1.2-71.5) and teacher ratings of executive function (OR = 5.3, 95% CI = 1.4-20.2) were associated with below-expected achievement. Mediation analysis showed IQ had indirect effects on writing (b = 1.5, 95% CI = 0.6-3.1) via attentional control; and on reading (b = 1.0, 95% CI = 0.2-3.2) and writing (b = 0.8, 95% CI = 0.1-2.5) via cognitive flexibility.Conclusions: Both low IQ and low executive function are associated with below-expected teacher-rated academic achievement in children born very preterm. IQ may influence academic achievement in part through executive function. [ABSTRACT FROM AUTHOR]

Background: Competent cardiac auscultation is a declining skill. Digital stethoscopes and hand-held echocardiography (HHE) are modern devices which may improve the accuracy of heart murmur recognition and diagnosis. Their incremental value compared to conventional examination has not been evaluated in depth. Objectives: Our aim was to quantify the utility of digital stethoscopes and HHE as teaching aids to improve medical students' diagnostic accuracy in the evaluation of heart murmurs using a novel clinically weighted scoring system. Design: This pilot study involved eight medical students and eight patients with heart murmurs. Four patients were examined at 2 sessions, 1 week apart. Medical students were randomised into two groups: the 'intervention group' examined patients with a standard and digital stethoscope, and then received demonstration of the valvular lesion with HHE to illustrate the diagnosis. The 'control group' used a standard stethoscope only and were taught using traditional methods. Students' scores were compared to a 'gold standard' derived from a consensus of auscultation findings of three cardiologists. Results: Overall the mean percent correct of total possible score was 65.4% (SD8.4). Using a mixed models ANOVA approach to repeated measures, the mean [95% CI] increase from training to validation period for the control group was 2.5% [−11.5, 16.5] P(Tukey) = 0.95 and 15.8% [1.7,29.8] P(Tukey) = 0.027 for the intervention group. Between the validation and training sessions for both groups, there was an increase of 9.1% [1.82, 16.4] in scores (p = 0.018). The mean [95% CI] difference in scores of the control and intervention groups was 1.9% [−5.4, 9.2] (p = 0.59). The Cohen's effect size estimate was 0.9. Conclusion: Digital stethoscopes and hand-held echo may be useful devices for teaching cardiac auscultation. This pilot study provides a novel study design, a heart murmur grading system, and data that will help develop definitive studies to assess new teaching techniques for cardiac auscultation using digital technology. [ABSTRACT FROM AUTHOR]

The article presents a study which examined whether increasing calcium intake can prevent fractures and whether there are differences between the effects of dietary sources of calcium and calcium supplements on fracture prevention. In the study, databases from Ovid Medline, Embase and Pubmed were examined. Based on the results, higher calcium intake was not associated with fracture risk.