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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]

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]

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]

OBJECTIVE -- Women with type 2 and type 1 diabetes have differing risk factors for pregnancy loss. We compared the rates and causes of pregnancy loss in women with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS -- We utilized prospectively collected data on all pregnancies in a 20-year period (1986-2005) from a single center with a high prevalence of type 2 diabetes. Pregnancy losses included terminations for medical reasons and deaths up to 1 month postpartum but not spontaneous pregnancy losses <20 weeks' gestation. RESULTS -- There were 870 pregnancies in women with known diabetes (330 with type 1 and 540 with type 2 diabetes) and 325 in women with diabetes diagnosed in pregnancy but persisting postpartum (97% type 2 diabetes). The rate of pregnancy loss was similar in type 1 and type 2 diabetes (2.6 vs. 3.7%, P = 0.39), but the causes of pregnancy loss differed. In type 1 diabetes >75% were attributable to major congenital anomalies or prematurity; in type 2 diabetes > 75 % were attributable to stillbirth or chorioamnionitis (P = 0.017). Women with type 2 and type 1 diabetes had similar A1C at presentation and near term, but the former were older (P < 0.001) and more obese (P < 0.0001). CONCLUSIONS -- There are significant differences in the main causes of pregnancy loss in women with type 1 and type 2 diabetes. The higher rates of stillbirth in women with type 2 diabetes, suggest that other features, such as obesity, contribute significantly to pregnancy losses. [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]

A letter is presented which described a study that investigated the prevalence of gout in patients with diabetes. The clinical factors linked to gout in a large community-based group of patients with diabetes was likewise examined. Data analyzed was from the Diabetes Care Support Service (DCSS). The findings reportedly supported previous results that have illustrated an inverse relationship between serum urate and hemoglobin A1c (HbA1c) in the general population.

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]

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]

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]

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.

Abstract: We continue our study of partitions of the full set of triples chosen from a -set into copies of the Fano plane (Fano partitions) or copies of the affine plane (affine partitions) or into copies of both of these planes (mixed partitions). The smallest cases for which such partitions can occur are where Fano partitions exist, where affine partitions exist, and where both affine and mixed partitions exist. The Fano partitions for and the affine partitions for and 10 have been fully classified, into 11, two and 77 isomorphism classes, respectively. Here we classify (1) the sets of i pairwise disjoint affine planes for , and (2) the mixed partitions for into their 22 isomorphism classes. We consider the ways in which these partitions relate to the large sets of . [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]

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]

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.

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]

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]

Objective: Preclinical studies, observational studies, and clinical trials suggest that thiazolidinediones (TZDs) reduce bone mineral density (BMD) and increase fracture risk. Most of the evidence on the skeletal effects of TZDs is from studies of rosiglitazone. We set out to investigate the magnitude and etiology of the adverse skeletal effects of pioglitazone. Design: Double-blind, randomized controlled trial. Trial registration: Australia New Zealand Clinical Trials Registry, actr.org.au Identifier: ACTRN12607000610437, date of registration 28/11/07. Methods: A total of 86 people with type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT), median age 64 years, were randomized to receive either pioglitazone 30 mg/day or placebo for 1 year, in addition to their usual diabetes treatments. The primary outcome was change in lumbar spine BMD; secondary outcomes included changes in BMD at other sites and in biochemical markers of bone turnover. Results: Change in spine BMD was not altered by treatment with pioglitazone (Ptreatment × time = 0.5). After 1 year, the mean (95% CI) between-groups difference in lumbar spine BMD was --0.7% (--2.1, 0.7). Pioglitazone increased bone loss at the proximal femur (Ptreatment × time = 0.03). After 12 months, the between-groups difference in total hip BMD was --1.2% (--2.1, 0.2). Pioglitazone did not alter change in BMD at other skeletal sites, nor did it affect changes in the levels of either of the biochemical markers of bone turnover, procollagen type 1 N-terminal propeptide, or ß-C-terminal telopeptide of type 1 collagen. Conclusions: Over 1 year, treatment with pioglitazone 30 mg/day did not produce consistent effects on either BMD or bone turnover in people with T2DM or IGT. The mechanism(s) by which pioglitazone increases fracture risk in T2DM is unclear. [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]

Objective: To determine the effect of pioglitazone on bone marrow fat in humans. Design: Twenty participants in a double-blind, randomized, placebo-controlled trial of the skeletal effects of pioglitazone 30 mg daily in type 2 diabetes mellitus (T2DM) entered a 6-month substudy evaluating bone marrow fat. Main outcome measures were bone marrow fat in lumbar spine (L4) and proximal femur (intertrochanteric region), measured using magnetic resonance (MR) imaging, and bone mineral density (BMD), measured using dual-energy X-ray absorptiometry. Results: After 6 months, change in the fourth lumbar vertebra (L4) bone marrow lipid fraction, assessed using two different methods, was greater in the pioglitazone group than in the placebo group (Dixon method: mean (95% CI) change from baseline pioglitazone 1.3% (K0.3, 2.9), placebo K0.2% (-0.8, 0.4), P=0.06; MR spectroscopy: pioglitazone 2.5% (0.4, 4.7), placebo -1.1% (-3.7, 1.4), P=0.02). Similarly, the change in lipid fraction in the intertrochanteric region was greater in the pioglitazone group (Dixon method: mean (95% CI) change from baseline pioglitazone 1.3% (0.6, 1.9), placebo K0.8% (-1.8, 0.2), P=0.001). Within the pioglitazone group, there was no evidence of a significant relationship between change in marrow lipid fraction and BMD. Conclusions: Short-term treatment with pioglitazone increases bone marrow fat in patients with T2DM. [ABSTRACT FROM AUTHOR]

Objectives. To develop a method of scoring bone erosion in the feet of patients with gout using CT as an outcome measure for chronic gout studies, consistent with the components of the OMERACT filter.Methods. Clinical assessment, plain radiographs and CT scans of both feet were obtained from 25 patients with chronic gout. CT scans were scored for bone erosion using a semi-quantitative method based on the Rheumatoid Arthritis MRI Scoring System (RAMRIS). CT bone erosion was assessed at 22 bones in each foot (total 1100 bones) by two independent radiologists. A number of different models were assessed to determine the optimal CT scoring system for bone erosion, incorporating the frequency of involvement and inter-reader reliability for individual bones.Results. An optimal model was identified with low number of bones required for scoring (seven bones/foot), inclusion of bones over the entire foot, high reliability and ability to capture a high proportion of disease. This model included the following bones in each foot: first metatarsal (MT) head, second to fourth MT base, cuboid, middle cuneiform and distal tibia (range 0–140). Scores from this model correlated with plain radiographic damage scores (r = 0.86, P < 0.0001) and disease duration (r = 0.42, P < 0.05). Scores were higher in those with clinically apparent tophaceous disease than in those without tophi (P < 0.0001).Conclusions. We have developed a preliminary method of assessing bone erosion in gout using conventional CT. Further testing of this method is now required, ideally in prospective studies to allow analysis of the sensitivity to change of the measure. [ABSTRACT FROM AUTHOR]

Background. In this study, our main goal was to determine whether an integrated, community-based model of care using culturally appropriate health-care assistants to manage hypertension in Māori and Pacific patients with diabetes and chronic kidney disease (CKD) is more effective than conventional care in achieving blood pressure (BP) targets and delaying progression of cardiac and renal end-organ damage.Methods. Sixty-five Māori and Pacific patients (aged 47–75 years) with type 2 diabetes, moderate CKD (>0.5 g proteinuria/day, serum creatinine 130–300 µmol/l) and hypertension were randomized to usual care (n = 32) or community/intervention care (n = 33) for 12 months. Community care patients were visited monthly by a nurse-led health-care assistant for BP measurement. Antihypertensives were adjusted using a stepwise protocol, aiming for a BP <130/80 mmHg. Office BP and renal and echocardiographic parameters were measured at baseline and 12 months.Results. Baseline characteristics including office BP, renal and echocardiographic parameters, and number of antihypertensives were well matched in both groups. By 12 months, the community care patients had achieved a significantly greater reduction in office systolic BP (−21 ± 26 mmHg vs −12 ± 20 mmHg, P = 0.04) and in 24-h urine protein (−1.4 ± 2.6 g vs +0.1 ± 2.8 g, P = 0.04). The number of prescribed antihypertensives was greater in these patients at 12 months (3.4 ± 1.1 vs 2.3 ± 1.0, P < 0.01). Left ventricular (LV) mass and left atrial (LA) volume progressed in the usual care group, but not in the intervention group (P < 0.05).Conclusion. This novel model of care is more effective than conventional care in lowering systolic BP and reducing cardiac and renal end-organ damage in these high-risk patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- In genetically diabetes-prone populations, maternal diabetes during pregnancy increases the risk of their children developing diabetes and obesity (the vicious cycle of type 2 diabetes). Fetal hyperinsulinemia at birth acts as a marker of this risk. We therefore examined whether cord insulin and leptin concentrations are increased in offspring of Maori and Pacific Island mothers with type 2 and gestational diabetes mellitus (GDM) and varying degrees of glycemic control (HbA1c). RESEARCH DESIGNS AND METHODS -- Maori and Pacific Island mothers were prospectively recruited at Middlemore Hospital, South Auckland. Cord blood was taken from umbilical vein at birth from singleton babies born after 32 weeks of gestation to 138 mothers with GDM, 39 mothers with type 2 diabetes, and 95 control mothers. RESULTS -- Babies born to mothers with both type 2 diabetes and GDM had higher birth weight and skinfold thickness and markedly higher concentrations of insulin (median [inter-quartile range] type 2 diabetes 77 pmol/l [42-143], GDM 67 pmol/l [42-235], and control subjects 33 pmol/l [18-62]; P < 0.001) and leptin (type 2 diabetes 39 ng/ml [18-75], GDM 31 ng/ml [17-58], and control subjects 13 ng/ml [8-22]; P < 0.001) in cord blood. Cord insulin concentrations > 120 pmol/l were found in 29% of offspring of mothers with GDM and 31% of mothers with type 2 diabetes. Many mothers with GDM had abnormalities of glucose tolerance postpartum (20% type 2 diabetes, 34% impaired glucose tolerance or impaired fasting glucose). Higher cord insulin (57 pmol/l [40-94]) and leptin (26 ng/ml [17-39]) concentrations were found even in offspring of GDM mothers with normal glucose tolerance postpartum. CONCLUSIONS-- Raised cord insulin and leptin concentrations are a common finding in offspring of mothers with type 2 diabetes and GDM in this population. [ABSTRACT FROM AUTHOR]

: ObjectivesThe purpose of this study was to determine the effect of amino-terminal pro-brain natriuretic peptide (N-BNP) on the diagnostic accuracy of heart failure (HF) in primary care.: BackgroundThe accurate diagnosis of patients with suspected HF presenting in primary care is difficult. Amino-terminal pro-brain natriuretic peptide is present in high levels in cardiac dysfunction and may improve the diagnostic accuracy of HF in primary care.: MethodsThe Natriuretic Peptides in the Community Study was a prospective, randomized controlled trial of the effect of N-BNP on the accuracy of HF diagnosis. Patients presenting to their general practitioner (GP) with symptoms of dyspnea and/or peripheral edema were included. The GPs formulated an initial diagnosis based on clinical assessment. All patients underwent a full cardiologic assessment that included echocardiography and N-BNP. Each patient was randomized to the BNP group (GP received the N-BNP result) or the control group (GP did not receive the N-BNP result). Patients were then reviewed by their GP, and their diagnosis was reviewed. The primary end point was the accuracy of the GPs'' diagnoses compared with the panel standard.: ResultsA total of 305 patients were included; mean age was 72 years, 65% were female. Seventy-seven patients met the panel criteria for HF. The diagnostic accuracy improved 21% in the BNP group and 8% in the control group (p = 0.002). The main impact of N-BNP measurement on diagnostic accuracy was the GPs'' correctly ruling out HF. The number needed to diagnose by N-BNP measurement was seven patients.: ConclusionThis study demonstrates that N-BNP measurement significantly improves the diagnostic accuracy of HF by GPs over and above customary clinical review. [Copyright &y& Elsevier]

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]

Presents a commentary on a study by Paul Poirier et al., published in a 2001 issue of `Diabetes Care,' dealing with pseudonormal diastolic filling unmasked with glyceryl trinitrate in men who are free of clinical heart disease and have well-controlled diabetes.

Summary: Objectives: To define local risk factors and outcomes for bacteremia with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) at a tertiary hospital in New Zealand. Methods: Patients with ESBL-E bacteremia were compared to matched control patients with non-ESBL-producing Enterobacteriaceae bacteremia. Patients were matched by onset of bacteremia (community vs. hospital), site of blood culture collection (peripheral vs. via central line), and infecting organism species. Results: Forty-four cases with matched controls were included. Eight- and 30-day mortality was higher in cases than controls (27% vs. 7%; p =0.011 and 34% vs. 11%, p =0.011). Twenty-one cases (48%) were community-onset. Community-onset cases were associated with urinary tract infection, whereas hospital-onset cases were associated with central line infection, intensive care admission, and Enterobacter cloacae. Independent risk factors for ESBL-E bacteremia were fluoroquinolone exposure (odds ratio (OR) 6.56, 95% confidence interval (CI) 1.79–24), first-generation cephalosporin exposure (OR 12.3, 95% CI 1.01–148), and previously-known colonization with ESBL-E (OR 46.2, 95% CI 3.45–619). Conclusions: The association with fluoroquinolone exposure suggests that measures to reduce unnecessary use may be an effective preventative strategy. Known colonization with ESBL-E is a strong risk factor for ESBL-E bacteremia, and colonization status should be taken into consideration when choosing empirical therapy. [ABSTRACT FROM AUTHOR]