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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]

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]

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]

Aims To describe changes in heart failure (HF) epidemiology in New Zealand between 1988 and 2008 using the number of days alive and out of hospital after a first hospitalization for HF, and to use these data to evaluate the overall impact of changing patterns of hospitalization and survival. Methods and results We performed a population analysis of all HF hospitalization and mortality data from 1 January 1988 to 31 December 2008 in New Zealand. The main outcome measures were: days alive and out of hospital, age standardized hospitalization rates, and mortality after an index hospitalization for HF. The number of days alive and out of hospital at 2 years increased by 2 months over the two decades of the study (from 448.8 to 511.3 days). Age standardized index HF hospitalization rates increased from 1988 to 1999, and declined thereafter, current rates are 106.9/100 000 for women and 174.3/100 000 for men. Patient age at index admission progressively increased, and hospital length of stay decreased. Mortality rates progressively decreased until 2000, but there has been no further decrease since then. Total hospital days have decreased up to 2008. Conclusion There have been major changes in the epidemiology of HF in New Zealand between 1988 and 2008, during which time there have been important changes in HF management. Despite increasing age, hospitalization rates are now declining and patients with HF are surviving longer out of hospital and with fewer hospital days. These results support the need for continued emphasis on delivery of effective community-based care for patients with this long-term condition. [ABSTRACT FROM PUBLISHER]

Abstract: Background and objective: Doppler echocardiographic assessment of diastolic filling provides a non-invasive estimate of left ventricular (LV) filling pressure and the most advanced diastolic filling grade, the restrictive filling pattern (RFP), has been linked to prognosis in patients post acute myocardial infarction (AMI) and with heart failure (HF). There remains some uncertainty about the prognostic role of RFP in patients with varied levels of systolic function. The objective of this collaboration is to determine whether the presence of RFP offers additional prognostic information over LV systolic function, symptoms or other clinical factors in patients post AMI or with HF. Methods: The Meta-analysis Research Group in Echocardiography (MeRGE) has been established in order to test this through two individual patient meta-analyses. Prospective studies that enrolled patients with either established HF or post AMI and included Doppler-echocardiography and outcome data will be merged into two large datasets (3739 AMI patients and 3540 HF patients) in order to evaluate the independent effects of RFP upon total and cardiovascular mortality using Kaplan–Meier survival analysis methods and Cox proportional Hazards model for multi-variate analysis. Survival will be examined within different bands of LV systolic function based upon ejection fraction (EF). Implications: This unique dataset will provide a very large cohort of patients, which will be adequately powered to provide new and prognostically important information to further aid risk stratification in these two high-risk patient groups. [Copyright &y& Elsevier]

Abstract: Background: Several studies have reported that the presence of a restrictive filling pattern (RFP) is associated with poor outcome in patients with heart failure (HF). These studies, of variable sample size, have involved different HF patient groups with variable associated mortality rates and follow-up times, and while powered for effects on combined end-points such as death or hospital admission, many were underpowered to reliably determine the overall effect of the RFP on total mortality. Consequently, we performed a meta-analysis to determine the mortality associated with RFP in patients with HF. Methods: We searched several online medical databases for prospective studies of patients with HF. All authors were requested to confirm their data. All-cause mortality was compared between RFP and non-restrictive filling patterns (Non-RFP). Review Manager version 4.2.7 software was used for the analysis. Results: 3024 patients in 27 studies were identified (379 idiopathic cardiomyopathy, 2645 mixed aetiology HF). Average follow-up was between 3 months and 5 years. 1284 (42%) patients had RFP at baseline. 688 deaths occurred and the overall odds ratio for death was 4.36 (CI 3.60, 5.04); idiopathic group: 6.65 (CI 3.86, 11.47); mixed aetiology group: 4.10 (CI 3.34, 5.04). The overall odds ratio for death/transplantation was 4.87 (CI 4.04, 5.86); idiopathic group: 7.62 (CI 4.50, 12.92); mixed aetiology group: 4.56 (CI 3.74, 5.56). Conclusions: Restrictive filling pattern is associated with a four-fold increase in mortality in patients with HF and thus should be an important part of the echocardiographic assessment of such patients. [Copyright &y& Elsevier]

Background: To review medical and ophthalmic findings of primary diabetic vitrectomy patients to examine indices important in progression to fellow eye surgery. Methods: A retrospective analysis was undertaken of all diabetic patients undergoing vitreoretinal surgery at Auckland Public Hospital between January 1992 and July 1996. Kaplan−Meier survival analysis was performed along with univariate and multivariate (Cox Proportional Hazards) data analysis. Results: One hundred and fourteen primary diabetic vitrectomy cases were reviewed with mean follow-up duration of 4 years. Thirty-eight per cent ( n = 43) of the study group underwent fellow eye surgery at a mean time of 1.6 years after first eye surgery. Fourteen patients were already blind in the fellow eye at baseline, and five patients refused second eye surgery on intention to treat. Thus there were 62 (54%) patients with severe (surgical threshold) fellow eye disease diagnosed within the follow-up period. The presence of either tractional retinal detachment or combined rhegmatogenous/tractional retinal detachment but without vitreous haemorrhage in the presenting eye was, in this series, a risk factor for fellow eye surgery (OR 5.56; 95% CI 1.96−15.8). Maori and Pacific Islander ethnicity was significantly associated with traction retinal detachment (OR 2.23; 95% CI 1.05−4.7). At data analysis 57% ( n = 60) of the study patients had died. The mean time to death was 4.3 years, with 84% of these patients having evidence of renal disease at the time of their first eye surgery. Good visual function in at least one eye was maintained in many patients. Conclusions: A substantial proportion of diabetic vitrectomy patients require fellow eye surgery. Absence of vitreous haemorrhage in the presenting eye (i.e. tractional or combined rhegmatogenous/tractional retinal detachments but without vitreous haemorrhage) was predictive of need for fellow eye surgery. The need for diabetic vitrectomy correlates with poor survival in this study population. [ABSTRACT FROM AUTHOR]

Aims: To investigate the effects of tissue harmonic imaging (THI) and contrast chamber opacification (LVO) upon measurement variability and reproducibility of echocardiographic left ventricular (LV) volume and ejection fraction (EF) measurements in patients with heart failure (HF). Background: Echocardiography is often used in HF patients to determine LV volumes and EF. However, current echo methods are variable and may not be applicable for repeat testing in individual patients. THI and LVO have both been shown to improve endocardial visualisation, but it remains to be determined whether this results in better measurement reproducibility. Methods: Thirty-one HF patients and 30 control subjects underwent echocardiography on two separate days. LV volumes were measured under four different imaging conditions: fundamental, THI, LVO and LVO with ECG-triggered Power Doppler. Chamber opacification, pulmonary transit time (PTT), endocardial enhancement, reproducibility and bias were assessed. Results: Chamber opacification was inferior and the PTT longer in the HF patients. PTT was related to LV volumes, EF, jugular venous pressure and mitral filling pattern. THI improved endocardial visualisation, and although LVO improved endocardial visualisation in the controls, it offered no benefit over THI in the HF patients. LV volumes and EF were different for each method and THI was the least variable method for repeat measurements. Conclusions: THI improved endocardial visualisation and was the least variable of the techniques. LVO offered no further advantage in patients with HF and thus cannot be routinely advocated and since LV volumes and EF were different for each, these methods are neither comparable nor interchangeable for follow-up assessments. [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]

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: 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: 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]

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]

The article presents a study which evaluates the cellular framework of gouty tophus and determines the incidence of cytokines in the disease. It includes the collection of paraffin-embedded tophus from 12 patients after surgical removal of tophi followed by its analysis through quantitative immunochemistry. Results of the study reveal the presence of multinucleated cells in the corona area and mast cells in tophus samples with the same desnsities.

Background: Atrial fibrillation (AF) and congestive heart failure (HF) often coexist, but there is conflicting data regarding the association of AF with outcome in HF. To examine this further we have evaluated the prognostic effect of AF in two complementary CHF populations; a population based data set of 55,106 patients admitted to hospital with CHF, and a cohort of 197 patients recruited after a hospital admission with HF into a management clinical trial. Methods: Firstly, data for all hospital admissions in New Zealand from 1988 to 1997 were obtained. Using coding data, 55,106 first admissions for HF were identified, the presence of AF was determined by secondary diagnosis coding, and all cause mortality was obtained. Secondly, patients enrolled in the Auckland Heart Failure Management Study were evaluated for the presence or absence of AF, and for all cause mortality at three years. Results: Mortality at 30 days, 6 and 12 months was significantly lower for AF patients compared to sinus rhythm (SR) in the national admissions cohort. In the clinical trial cohort the presence of AF was also associated with lower three-year mortality, although this difference was not seen when the groups were stratified by Doppler mitral filling pattern (a restrictive filling pattern was associated with reduced longevity compared to SR, non-restrictive or AF). Conclusions: This data shows that the presence of AF in two general HF populations in New Zealand is not associated with an adverse prognosis. HF severity, and in particular a restrictive filling pattern, remain powerful predictors of mortality. [Copyright &y& Elsevier]

We sought to study the relationship between left ventricular (LV) size and body composition in male endurance athletes and age-matched control subjects.Endurance training is associated with increases in both left ventricular mass (LVM) and left ventricular end-diastolic dimension (LVEDD) in athletes. In other populations, LVM is independently predicted by fat-free mass (FFM). We hypothesized that the increase in LV size and mass observed with training may be a normal response to increased FFM.Twelve young and 18 older male endurance athletes and 10 young and 18 older untrained men underwent exercise testing, echocardiography, and dual-photon x-ray absorptiometry body composition analysis. Univariate correlates (Spearman) and multivariate determinants of LVM and LVEDD were sought from: height, height1.4, height2.7, height3.0, body surface area (BSA), FFM, weight, and body mass index. Un-indexed and indexed LVM and LVEDD were then compared.Athletes were of a similar age, weight, and height, but had higher FFM and maximum oxygen uptake than untrained men. Both LVM and LVEDD were correlated with body size, including FFM, BSA, weight, and height (all p < 0.05). On multivariate analysis, FFM was the only independent predictor of both LVM (R2 = 0.36, p < 0.001) and LVEDD (R2 = 0.35, p < 0.001). Furthermore, LVM and LVEDD (un-indexed and indexed to BSA and height) were different between athletes and non-athletes, but not when indexed to height2.7 or FFM.Both LVM and LVEDD are predicted by FFM in endurance athletes, and when indexed to FFM, no training-related differences were observed. Thus, the extent of LV remodeling (athletic heart) in trained individuals may reflect a normal physiologic response to increased FFM induced by training. [Copyright &y& Elsevier]

: ObjectivesWe sought to investigate whether pseudonormal (PN) filling was associated with death or hospital admission in patients with congestive heart failure (CHF).: BackgroundThe high mortality rate associated with CHF is related to many clinical and echocardiographic variables. In particular, a short mitral deceleration time and restrictive diastolic filling predict death and/or hospital admission. We hypothesized that differentiating patients with nonrestrictive filling might identify an intermediate PN group that may be associated with intermediate risk.: MethodsA total of 115 patients admitted to the hospital for exacerbation of CHF symptoms underwent pre-discharge Doppler echocardiography to determine mitral inflow (before and after preload reduction) and pulmonary venous return. Patients were followed up for one year, and all-cause mortality and re-admission data were analyzed.: ResultsThe classification of filling patterns was: abnormal relaxation (AR) in 46 (40%) patients, pseudonormal (PN) filling in 42 (36.5%) patients and restrictive filling pattern (RFP) in 27 (23.4%) patients. When comparing the RFP group with the AR group, all-cause mortality was higher (38.4% vs. 17.4%, p = 0.033), hospital admission was higher (70.3% vs. 54.3%, p = 0.073), death/hospital admission was higher (77.8% vs. 56.5%, p = 0.02), CHF hospital admission was higher (40.7% vs. 15.2%, p = 0.01) and death/CHF hospital admission was higher (62.9% vs. 26.1%, p = 0.0005). Mortality in the PN group was not significantly different from that in the two other groups, but re-admissions were higher than the AR group (76.2% vs. 54.3%, p = 0.006), as was death/re-admission (78.6% vs. 56.5%, p = 0.004) and death/CHF re-admission (47.6% vs. 26.1%, p = 0.03). Re-admissions in the PN and RFP groups were comparable.: ConclusionsIn a general hospital population of older patients with CHF, PN filling was associated with hospital admission rates similar to those seen with restrictive filling. The combined end point of death/CHF hospital admission was similar for restrictive filling and AR. Measurement of these variables is easy to add to routine clinical echocardiography and may provide important prognostic information in a wide range of patients with CHF. [Copyright &y& Elsevier]

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]

The authors discuss inconsistencies in predicted fracture risk in elderly people. They state that there are significant differences between risk estimates from different calculators used by doctors and the inclusion of the competing risk of mortality in fracture risk calculators for elderly people give widely different results. They suggest that for elderly patients, clinicians should use calculators that provide fracture risk estimates for shorter time periods.

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]

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.

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]

Objectives. Bone erosion has been linked with tophus deposition in gout but the roles of osteitis (MRI bone oedema) and synovitis remain uncertain. Our aims in this prospective 3 T MRI study were to investigate the frequency of these features in gout and determine their relation to one another.Methods. 3 T MRI scans of the wrist were obtained in 40 gout patients. Scans were scored independently by two radiologists for bone oedema, erosions, tophi and synovitis. Dual-energy CT (DECT) scans were scored for tophi in a subgroup of 10 patients.Results. Interreader reliability was high for erosions and tophi [intraclass correlation coefficients (ICCs) 0.77 (95% CI 0.71, 0.87) and 0.71 (95% CI 0.52, 0.83)] and moderate for bone oedema [ICC = 0.60 (95% CI 0.36, 0.77)]. Compared with DECT, MRI had a specificity of 0.98 (95% CI 0.93, 0.99) and sensitivity of 0.63 (95% CI 0.48, 0.76) for tophi. Erosions were detected in 63% of patients and were strongly associated with tophi [odds ratio (OR) = 13.0 (95% CI 1.5, 113)]. In contrast, no association was found between erosions and bone oedema. Using concordant data, bone oedema was scored at 6/548 (1%) sites in 5/40 patients (12.5%) and was very mild (median carpal score = 1, maximum = 45). In logistic regression analysis across all joints nested within individuals, tophus, but not synovitis, was independently associated with erosion [OR = 156.5 (21.2, >999.9), P < 0.0001].Conclusion. Erosions were strongly associated with tophi but not bone oedema or synovitis. MRI bone oedema was relatively uncommon and low grade. These findings highlight the unique nature of the osteopathology of gout. [ABSTRACT FROM PUBLISHER]

The class I phosphatidylinositol 3-kinases (PtdIns3Ks) mediate the effects of many hormones and growth factors on a wide range of cellular processes, and activating mutations or gene amplifications of class I PtdIns3K isoforms are known to contribute to oncogenic processes in a range of tumours. Consequently, a number of small-molecule PtdIns3K inhibitors are under development and in clinical trial. The central signalling role of PtdIns3K in many cellular processes suggests there will be on-target side effects associated with the use of these agents. To gain insights into what these might be we investigated the effect of extended daily dosing of eight small-molecule inhibitors of class Ia PtdIns3Ks. Animals were characterized in metabolic cages to analyse food intake, oxygen consumption and movement. Insulin tolerance and body composition were analysed at the end of the experiment, the latter using Echo MRI. Bone volume and strength was assessed by micro- CT and three-point bending, respectively. Surprisingly, after sustained dosing with pan-PtdIns3K inhibitors and selective inhibitors of the p110α isoform there was a resolution of the impairments in insulin tolerance observed in drug-naïve animals treated with the same drugs. However, pan-PtdIns3K inhibitors and selective inhibitors of the p110α have deleterious effects on animal growth, animal behaviour and bone volume and strength. Together, these findings identify a range of on target effects of PtdIns3K inhibitors and suggest use of these drugs in humans may have important adverse effects on metabolism, body composition, behaviour and skeletal health. [ABSTRACT FROM AUTHOR]

. Purpose: To investigate the ability of optical coherence tomography (OCT) parameters of macular thickness (MT) and peripapillary retinal nerve fibre layer (RNFL) thickness to differentiate eyes with nonarteritic anterior ischaemic optic neuropathy (NAION) from uninvolved eyes and to identify the relationship between macular and RNFL parameters and visual field sensitivity (VFS). Methods: Thirty patients with unilateral NAION participated in a prospective observational cross-sectional study. Patients underwent Humphrey visual field (SITA Standard 24-2, HVF) testing and OCT to measure MT and RNFL. The contralateral uninvolved eye was used as controls. Areas under the receiver operating characteristic curves (AUROCs) of MT and RNFL for discriminating NAION from control eyes were also determined. The prespecified outcome measure was the correlation between RNFL, MT and mean deviation (MD). Results: Average RNFL and MT were thinner in NAION eyes: 72.8 μm versus 98.9 μm (p < 0.0001) and 231.9 μm (SD, 21.4) vs. 251.1 μm (SD, 14.8; p = 0.0001), respectively. The largest AUROCs were for average MT (0.87) and average RNFL thickness (0.88). Overall, macular parameters showed stronger correlation with VFS than RNFL parameters. The highest correlation was average MT (0.71; p < 0.0001) followed by RNFL parameter nasal quadrant RNFL (0.40; p = 0.030). Conclusion: Both MT and RNFL show strong correlations with level of VFS in NAION. Macular thickness showed more robust correlations with VF and provides strong surrogate marker of the level of damage in NAION. [ABSTRACT FROM AUTHOR]

Summary Objective Most longitudinal studies of bone mineral density (BMD) in HIV-infected cohorts have been of short duration, typically 1-2 years. Some studies, especially of cohorts treated with highly active antiretroviral therapy (HAART), report short-term stable or increasing BMD, but other studies, often in cohorts initiating HAART, report short-term losses in BMD. We assessed BMD changes over the medium term in HIV-infected men already established on HAART at baseline. Design Six-year, prospective, longitudinal study. Subjects Forty-four HIV-infected men treated with HAART and 37 uninfected, healthy controls. Measurements Participants had measurements of BMD at baseline, 2 and 6 years. Results In the HIV-infected men at baseline, the mean age was 49 years, the mean duration of infection was 8 years, and the mean duration of HAART was 50 months. Over 6 years of follow-up, there was a greater increase in lumbar spine BMD (5·3%, 95% CI 3·8-6·5%) in the HIV-infected men compared with controls (0·3%, 95% CI −1·0 to 1·6%), P < 0·001. There was no difference between the groups in the change in BMD over time at the total hip (HIV group: −0·6%, 95% CI −1·7 to 0·4%, controls −1·0%, 95% CI −2·2 to 0%, P = 0·8) or at the total body (HIV group, 0·3%, 95% CI −0·3 to 1·0%; controls, 0·5%, 95% CI −0·2 to 1·1%, P = 0·15). Lean mass increased in the HIV group, but not in the controls. Conclusions There was no evidence of accelerated bone loss over 6 years in middle-aged, HIV-infected men treated with HAART. For such patients, routine monitoring of BMD is not necessary over the short/medium term. [ABSTRACT FROM AUTHOR]

Summary Objective Untreated Cushing's syndrome (CS) is associated with significant morbidity and mortality. However, recent operative series suggest low morbidity and mortality for CS, whereas population-based surveys report elevated mortality rates. We investigated the mortality and morbidity of CS in New Zealand. Design A nationwide retrospective survey of patients with CS between 1960 and 2005 managed at the four main endocrinology services. Patients A total of 253 patients with CS were identified, excluding adrenal carcinoma and malignant ectopic CS. Measurements The primary outcome was the standardized mortality ratio (SMR), comparing the observed number of deaths with the expected number for the population matched for age, sex and duration of follow-up. Secondary outcomes were the change in prevalence of co-morbidities at presentation and at final follow-up. Results The approximate prevalence and incidence of CS was 79/million and 1·8/million/y. The mean age at presentation was 39 year, and median duration of follow-up was 6·4 year (range 0-46). Overall, 89% achieved biochemical cure at last follow-up, with >90% achieving biochemical cure for CS from adrenal adenoma and pituitary causes. Thirty-six patients died during follow-up compared with 8·8 expected deaths (SMR 4·1, 95%CI 2·9-5·6). While hypertension, sexual dysfunction, myopathy and mild psychiatric illness were significantly reduced after treatment, hypertension, diabetes mellitus, moderate or major psychiatric illness, and osteoporosis were common at final follow-up. Conclusion CS is associated with both high mortality and a high prevalence of co-morbidities, even when biochemical cure rates are between 80% and 90%. [ABSTRACT FROM AUTHOR]

Abstract: Background: Meta-analyses are increasingly used to summarise observational data however a literature meta-analysis (LMA) may give different results to the corresponding individual patient meta-analysis (IPMA). This study compares the published results of equivalent LMAs and IPMAs, highlighting factors that can affect the results and therefore impact on clinical interpretation of meta-analyses. Method: Univariate results from published meta-analyses of prospective observational outcome data were compared, as were the number of studies, patients and length of follow-up. The absolute difference in survival was calculated. The association between severe diastolic dysfunction (RFP) and death post acute myocardial infarction (AMI) and in chronic heart failure (HF) were used as clinical examples. Results: The IPMA hazard ratio was lower that the LMA odds ratio: AMI hazard ratio 2.67 (95% confidence interval 2.23 to 3.20), odds ratio 4.10 (3.38 to 4.99); HF hazard ratio 2.42 (2.06 to 2.83), odds ratio 4.36 (3.60 to 5.04). The IPMAs contained most of the studies from the LMAs as well as additional unpublished data, and a longer length of follow-up was available in the IPMAs (AMI 3.7 vs 2.6 yr, HF 4.0 vs 1.5yr). Restricting analysis to the same studies in both the LMA and IPMA resulted in a similar difference in effect sizes between methods to those found in the published analyses. Conclusions: The result of a meta-analysis is affected by whether study level or individual patient data have been used, and the variant of analysis that is required. Awareness and consideration of these factors is important for clinical interpretation of meta-analyses. [Copyright &y& Elsevier]

Background: Although brain natriuretic peptide (BNP) and E/Ea are closely related in heart failure (HF) patients and may be helpful to guide HF therapy, the response of E/Ea to changes in BNP over several weeks of intensive HF treatment optimisation is unknown. This study was designed to investigate this relationship. Methods and results: In 17 patients with decompensated HF, treatment was titrated to reduce the NT-proBNP level to <200pg/mL over 10 weeks. Paired NT-proBNP measurements and echocardiograms were performed at two weekly intervals during the study. Treatment titration was associated with a reduction in E/Ea (17.6±6.8S.D. to 13.7±5.0S.D., p =0.018) in keeping with the reduction in NT-proBNP (median 603 [S.E. 561] to 311 [S.E. 235], p =0.045). This relationship remained in those who responded to titration (reduction in NT-proBNP of ≥50%), and those who did not. The overall change in E/Ea was similar to the changes observed in NT-proBNP in each group however there appeared to be temporal differences in the changes in E/Ea and NT-proBNP. Conclusion: This pilot study demonstrates that the E/Ea decreases after NT-proBNP guided HF therapy. E/Ea may be a complementary target for HF therapy optimisation; this hypothesis should be further evaluated in larger scale randomised trials. [Copyright &y& Elsevier]

The article reports on the study that investigates the probability of recurrent osteoporotic fractures after a primary wrist fracture with other important primary fracture sites. The study evaluates the longitudinal health service records for the presence of fracture codes before and after bone mineral density (BMD) testing. It found that wrist fractures are the most common of the clinical osteoporotic fractures in patients referred for BMD testing. However, it reveals that the risk of recurrent fractures in the 10 years following a wrist fracture is substantially lower than the other osteoporotic fractures.

Purpose: To evaluate whether patients who have undergone trabeculectomy with mitomycin C have a different intraocular pressure (IOP) response profile after the water drinking test (WDT) from that of patients who are medically managed with a similar baseline IOP and level of visual field (VF) damage. Design: Prospective observational study. Participants: Thirty glaucoma patients with IOP controlled by trabeculectomy and 30 with medically treated glaucoma matched for level of VF damage and IOP at baseline (7–14 mmHg). Methods: All patients underwent the WDT, which involved drinking 1000 ml of water in 15 minutes. Main Outcome Measures: The IOP was measured before the WDT and subsequently at 15-minute intervals for 1 hour. The peak IOP with the WDT was compared between both groups using Tukey post hoc multiple comparison and paired t tests. Results: Baseline IOPs were 10.4±2.3 mmHg in surgically treated and 11.1±1.8 mmHg (P = 0.07) in medically treated eyes. After the WDT, mean IOPs in the surgically and medically treated groups were 10.7±2.3 mmHg and 14.6±2.2 mmHg. Mean maximum IOPs were 11.7±2.6 mmHg and 17.3±2.7 mmHg in the surgically and medically treated groups, respectively (P<0.0001), increases of 12.5% and 56%. Ranges of IOP during the WDT were 2.2±1.3 mmHg and 5.6±1.9 mmHg in the surgically and medically treated patients (P<0.0001). Conclusions: Patients with advanced glaucoma who are medically controlled show greater IOP elevation and peak IOP after the WDT than eyes that have undergone trabeculectomy. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

Objective 25-hydroxyvitamin D (25OHD) levels are inversely related to body weight, and have been reported to decline with age and be lower in women than men. We hypothesized that these findings might be explained by effects of these variables on vitamin D binding protein (DBP) levels. We set out to determine the relationships between DBP and gender, 25OHD, body weight and body composition. Design Cross-sectional analysis. Patients One hundred healthy, middle-aged and older, community-dwelling men and women. Measurements All participants were measured for 25OHD, DBP, body weight, bone mineral density and body composition. Results Women had higher mean DBP levels than men but lower total 25OHD levels [DBP: women, mean (SD) 339 (36) mg/l, men 307 (71) mg/l, P = 0·005; 25OHD: women 67 (23) nmol/l, men 91 (39) nmol/l, P < 0·001]. In women, there were significant positive relationships between DBP and albumin ( r = 0·33) and 25OHD ( r = 0·34) whereas in men there were no significant relationships between DBP and any measured variables. There was no significant relationship between DBP and age, body weight, body mass index, fat mass or percentage fat in men or women. Conclusion We found no evidence to support the hypothesis that DBP levels are related to age, or adiposity. The changes in 25OHD levels with age, gender, or fat mass are not due to underlying relationships between DBP and these variables. This suggests that the relationships consistently observed between 25OHD and body composition and gender are of biological origin and not due to adaptation to changes in transport proteins. [ABSTRACT FROM AUTHOR]

Objective Recently we reported that human immunodeficiency virus (HIV)-infected Caucasian men treated with highly active antiretroviral therapy (HAART) have normal weight-adjusted bone mineral density (BMD), in contrast to most other cross-sectional analyses, which have reported low BMD in HIV-infected patients. We have now addressed the question of whether there is accelerated BMD loss over time in HIV-infected men. Design A 2-year, prospective, longitudinal study. Subjects Twenty-three HAART-treated, HIV-infected men and 26 healthy controls. Measurements All participants had measurements of BMD and bone-related laboratory parameters at baseline, and a repeat measurement of BMD at 2 years. Results In the HIV-infected men the mean age was 47 years, the mean duration of infection was 8·2 years, and the mean duration of HAART was 54 months. Over 2 years of follow-up, BMD increased from baseline in the HIV-infected men by 2·6% at the lumbar spine ( P = 0·05 vs. baseline), and remained stable at the total hip (mean change 0·1%, P > 0·99) and total body (mean change 0·6%, P = 0·39). Mean changes in BMD in the control group were 1·4% at the lumbar spine, –0·1% at the total hip, and –0·8% at the total body. The HIV-infected men lost less total body BMD than the control group ( P = 0·01). In the HIV-infected men, body weight remained stable over 2 years while fat mass decreased and lean mass tended to increase, whereas in the controls, body weight and fat mass increased while lean mass remained stable. Conclusions Accelerated bone loss does not occur in HIV-infected men treated with HAART. Monitoring of BMD in HIV-infected men may not be necessary. [ABSTRACT FROM AUTHOR]

Objective Recent studies have reported low bone mineral density (BMD) in patients infected with human immunodeficiency virus (HIV). Frequently these findings have been attributed to treatment with highly active antiretroviral therapy (HAART). We sought to determine whether BMD in HIV-infected men treated with HAART for at least 3 months is different from that in healthy controls, and, if so, what HIV-related factors might explain this finding. Design Cross-sectional analysis. Patients Fifty-nine HIV-infected Caucasian men treated with HAART, and 118 healthy community-dwelling controls. Each HIV-infected man was age-matched (within 5 years) to two controls. Measurements All participants had measurements of BMD and bone-related laboratory parameters. Results The mean duration of known HIV infection was 8·5 years, and of treatment with HAART was 52 months. There was no significant difference in mean BMD between groups at the lumbar spine (HIV group: 1·23 g/cm2, controls: 1·25 g/cm2; P = 0·53) or total body (HIV group: 1·18 g/cm2, controls: 1·20 g/cm2; P = 0·09). At the total hip the HIV-infected group had significantly lower BMD than the control group (HIV group: 1·03 g/cm2, controls: 1·09 g/cm2; P = 0·01). The HIV-infected group were, on average, 6·3 kg lighter than the controls. After adjusting for this weight difference, HIV infection was not an independent predictor of BMD at any site (lumbar spine P = 0·79; total hip P = 0·18; total body P = 0·76). Conclusions HIV-infected men treated with HAART are lighter than healthy controls. This weight difference is responsible for a small decrement in hip BMD. Overall, BMD is not significantly reduced in HIV-infected Caucasian men treated with HAART. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate relationships between the Disc Damage Likelihood Scale (DDLS), global and sectoral structural parameters provided by the Heidelberg Retina Tomograph (HRT), and global and regional functional loss in visual field (VF) testing. Design: Consecutive observational case series. Participants: One hundred ten eyes from 110 patients categorized as glaucoma, glaucoma suspect, or normal. Methods: Participants were examined clinically to grade the DDLS score and were tested with HRT and Swedish Interactive Threshold Algorithm standard 24-2 VF tests. All tests were performed within 6 months of each other by examiners masked to the other findings. For each patient, the eye with the worse mean deviation (MD) of the VF test was enrolled in the study. Each field was divided into 6 sectors based on a published scheme, and the MD for each sector was calculated. The relationships among clinical DDLS score, HRT parameters, and VF indexes were analyzed by correlation coefficients and linear regression analysis. Main Outcome Measures: The relationship between the DDLS score, global and sectoral optic disc (HRT) parameters, and global and sectoral VF MDs was evaluated. Results: The DDLS showed significant correlation with all global and sectoral VF indexes (r = −0.39 to −0.62, all Ps < 0.0001) and with sectoral rim area HRT measurements (r = −0.27 to −0.51, all Ps < 0.006). The DDLS correlated most strongly with superior and inferior regional data from HRT and VF, and less well with temporal and nasal data. Heidelberg Retina Tomograph rim area and rim volume were the only HRT parameters to correlate moderately with global VF MD (r = 0.30, P = 0.0018, and r = 0.28, P = 0.0030, respectively). Sectoral HRT rim area correlated moderately strongly with the corresponding sectoral VF MDs in the superior and inferior sectors (r = 0.35–0.46, P = <0.0001–0.04). Conclusion: Clinical disc assessment and laser tomographic data that determine the state of the neuroretinal rim are associated with sensitivity loss in VF testing in corresponding regions. [Copyright &y& Elsevier]

Abstract: Previously, we reported that people with elevated parathyroid hormone (PTH) levels due to primary hyperparathyroidism have increased body weight compared to eucalcemic controls. We sought to determine whether the same relationship between PTH and body weight exists in eucalcemic healthy postmenopausal women, and to investigate the relationships between components of body weight, PTH, vitamin D metabolites, and metabolic indices. We performed a cross-sectional analysis of 116 healthy community-dwelling postmenopausal women. Pearson correlation analysis was used to test for univariate linear relationships between variables, and stepwise multiple regression analysis to assess for multivariate relationships. We found that PTH was significantly positively correlated with body weight, regional and total fat mass, and percent body fat, and negatively correlated with activity levels, 25 hydroxyvitamin D (25OHD), dietary calcium intake, and serum phosphate. On multivariate analysis, PTH was positively related to percent body fat (P = 0.020; partial r 2 = 0.10) and negatively related to dietary calcium intake (P = 0.041; partial r 2 = 0.03) and serum phosphate (P = 0.026; partial r 2 = 0.04). Adjusting for vitamin D insufficiency or 25OHD levels did not affect the relationship between PTH and fat mass. For 25OHD, there were significant positive correlations with lumbar spine BMD and serum albumin, and significant negative correlations with PTH, total fat mass, trunk fat, and pelvic fat. On multivariate analysis, 25OHD was positively related to serum albumin (P = 0.008; partial r 2 = 0.07) and negatively related to pelvic fat mass (P = 0.014; partial r 2 = 0.05). Adjusting for PTH levels did not change the relationship between 25OHD and pelvic fat mass. We conclude that fat mass is a significant independent determinant of serum PTH levels, and that this relationship is independent of the inverse relationship between 25OHD and fat mass. This association between fat mass and PTH might contribute to the association between primary hyperparathyroidism and increased body weight. [Copyright &y& Elsevier]