Georgia Ntani

Risk factors associated with the isolation of colistin-resistant gram-negative bacteria: a matched case-control study.

Objective:The emergence of multidrug-resistant Gram-negative bacteria has led to the re-use of colistin, but resistance to this agent has already been reported. We aimed to investigate the potential risk factors for the isolation of colistin-resistant Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa from hospitalized patients. Design:Matched case-control study. Setting:Tertiary care hospital in Athens, Greece. Patients:Case patients were those who had provided a clinical specimen from which a colistin-resistant K. pneumoniae, A. baumannii, or P. aeruginosa was isolated. Controls were selected from a pool of patients who had susceptible to colistin isolates and were matched (1:1) to cases for species of microorganism and site of isolation. Susceptibility to colistin was determined with the Etest. Interventions:None. Measurements and Main Results:Data regarding patient demographics, comorbidities, admission to the intensive care unit, prior antibiotic use, and invasive procedures performed were analyzed as risk factors in a matched bivariable model. Variables significantly associated with colistin-resistant isolates (p < .05) were entered in a backward multivariable logistic regression model. Forty-one colistin-resistant unique patient isolates were identified from January 1, 2006, until March 31, 2007. These isolates represented infection in 35 of 41 patients. Risk factors significantly associated with the isolation of colistin-resistant isolates were age, duration of intensive care unit stay, duration of mechanical ventilation, surgical procedures, use of colistin, use of monobactams, and duration of use of third-generation cephalosporins. In the multivariable model, use of colistin was identified as the only independent risk factor (adjusted odds ratio = 7.78, p = .002). Conclusions:Colistin-resistant K. pneumoniae, A. baumannii, and P. aeruginosa pathogens may be encountered in clinical practice, in association with inappropriate colistin use. To prevent this phenomenon, colistin should be used judiciously, given that treatment options for colistin-resistant Gram-negative bacteria are limited.

An ESICM systematic review and meta-analysis of procalcitonin-guided antibiotic therapy algorithms in adult critically ill patients

PurposeWe sought to perform a systematic review and meta-analysis of procalcitonin(PCT)-guided antibiotic therapy algorithms for critically ill adult patients.MethodsWe performed a search in PubMed and in the Cochrane Central Register of Controlled Trials. Seven evaluable randomised clinical trials (RCTs) were identified and analysed. Primary outcomes included the duration of antibiotic therapy for the first episode of infection and 28-day mortality. Secondary outcomes included length of ICU stay, length of hospitalisation, antibiotic-free days within the first 28xa0days of hospitalisation, recurrences, and superinfections.ResultsData on the duration of antibiotic therapy for the first episode of infection were provided in five out of seven included RCTs, while data on 28-day mortality were provided in all of the included RCTs. Duration of antibiotic therapy for the first episode of infection was reduced in favour of PCT-guided treatment [pooled weighted mean difference (WMD)xa0=xa0−3.15xa0days, random effects model, 95xa0% confidence interval (CI) −4.36 to −1.95, Pxa0<xa00.001]. There was no difference in 28-day mortality between the compared arms [fixed effect model (FEM), odds ratioxa0=xa00.96, 95xa0% CI 0.79–1.15, Pxa0=xa00.63). Antibiotic-free days were increased within the first 28xa0days of hospitalisation in favour of the PCT-guided treatment arm (pooled WMDxa0=xa03.08xa0days, FEM, 95xa0% CI 2.06–4.10, Pxa0<xa00.001). No difference was found regarding the remaining outcomes. Sensitivity analyses including studies of higher quality and studies using the TRACE method to measure PCT yielded similar results.ConclusionsProcalcitonin-guided antibiotic therapy algorithms could help in reducing the duration of antimicrobial administration without having a negative impact on survival.

Increased fat mass is associated with increased bone size but reduced volumetric density in pre pubertal children

Recent studies have shown that obesity is associated with an increased risk of fracture in both adults and children. It has been suggested that, despite greater bone size, obese individuals may have reduced true volumetric density; however this is difficult to assess using two dimensional techniques such as DXA. We evaluated the relationship between fat mass, and bone size and density, in a population cohort of children in whom DXA and pQCT measurements had been acquired. We recruited 530 children at 6 years old from the Southampton Womens Survey. The children underwent measurement of bone mass at the whole body, lumbar spine and hip, together with body composition, by DXA (Hologic Discovery, Hologic Inc., Bedford, MA, USA). In addition 132 of these children underwent pQCT measurements at the tibia (Stratec XCT2000, Stratec Biomedical Systems, Birkenfeld, Germany). Significant positive associations were observed between total fat mass and both bone area (BA) and bone mineral content (BMC) at the whole body minus head, lumbar spine and hip sites (all p<0.0001). When true volumetric density was assessed using pQCT data from the tibia, fat mass (adjusted for lean mass) was negatively associated with both trabecular and cortical density (β=-14.6 mg/mm(3) per sd, p=0.003; β=-7.7 mg/mm(3) per sd, p=0.02 respectively). These results suggest that fat mass is negatively associated with volumetric bone density at 6 years old, independent of lean mass, despite positive associations with bone size.

Facilitated transporters mediate net efflux of amino acids to the fetus across the basal membrane of the placental syncytiotrophoblast

Non‐technical summary Fetal growth depends on transfer of amino acids from the mother to the fetus via the placenta: the interface between the maternal and fetal circulations. We know how amino acids enter the placenta from the maternal blood, but it was not known how the amino acids exit the placenta to reach the fetus. Our work has now provided the first experimental evidence for a novel transport system which provides net amino acid transport to the fetus and influences fetal growth.

Physical activity, calcium intake and childhood bone mineral: a population-based cross-sectional study.

SummaryIn a free-living cohort of 4-year old children, mean daily time in moderate–vigorous physical activity and daily calcium intake at 3xa0years, were positively related to hip bone size and density. Relationships between physical activity and bone indices were stronger when calcium intake was above compared with below median (966xa0mg/day).IntroductionWe examined the cross-sectional relationships between childhood physical activity, dietary calcium intake and bone size and density.MethodsChildren aged 4xa0years were recruited from the Southampton Womens Survey. They underwent measurement of bone mass by DXA (Hologic Discovery). Physical activity was assessed by accelerometry (Actiheart, Cambridge Neurotechnology Ltd, Cambridge, UK) for seven continuous days.ResultsFour hundred twenty-two children (212 boys) participated. In a cross-sectional analysis, after adjusting for gender, daily mean time(minutes per day) spent in moderate to very vigorous activity (MVPA) was positively related to hip BA (R2u2009=u20093%, pu2009<u20090.001), BMC (R2u2009=u20094%, pu2009<u20090.001), aBMD (R2u2009=u20093%, pu2009=u20090.001) and estimated vBMD (R2u2009=u20092%, pu2009=u20090.01), but not height (rsu2009=u20090.04, pu2009=u20090.42) or weight (rsu2009=u20090.01, pu2009=u20090.76). Mean daily calcium intake (assessed at 3xa0years old) positively predicted bone indices in those with a calcium intake below the median (966xa0mg/day), but there was a much attenuated relationship in those above this. These associations persisted after inclusion of total energy, protein and phosphorus in multivariate models. The relationships between MVPA and bone indices were stronger in children with calcium intakes above the median. Thus, for aBMD, the variance explained by MVPA when daily calcium intake was below the median was 2% (pu2009=u20090.1) and above median was 6% (pu2009=u20090.001).ConclusionsThese results support the notion that adequate calcium intake may be required for optimal action of physical activity on bone development and that improving levels of physical activity and calcium intake in childhood may help to optimise accrual of bone mass.

Childhood Bone Mineral Content Is Associated With Methylation Status of the RXRA Promoter at Birth

Maternal vitamin D deficiency has been associated with reduced offspring bone mineral accrual. Retinoid‐X receptor‐alpha (RXRA) is an essential cofactor in the action of 1,25‐dihydroxyvitamin D (1,25[OH]2‐vitamin D), and RXRA methylation in umbilical cord DNA has been associated with later offspring adiposity. We tested the hypothesis that RXRA methylation in umbilical cord DNA collected at birth is associated with offspring skeletal development, assessed by dual‐energy X‐ray absorptiometry, in a population‐based mother‐offspring cohort (Southampton Womens Survey). Relationships between maternal plasma 25‐hydroxyvitamin D (25[OH]‐vitamin D) concentrations and cord RXRA methylation were also investigated. In 230 children aged 4 years, a higher percent methylation at four of six RXRA CpG sites measured was correlated with lower offspring bone mineral content (BMC) corrected for body size (βu2009=u2009−2.1 to −3.4u2009g/SD, pu2009=u20090.002 to 0.047). In a second independent cohort (nu2009=u200964), similar negative associations at two of these CpG sites, but positive associations at the two remaining sites, were observed; however, none of the relationships in this replication cohort achieved statistical significance. The maternal free 25(OH)‐vitamin D index was negatively associated with methylation at one of these RXRA CpG sites (βu2009=u2009−3.3 SD/unit, pu2009=u20090.03). Thus, perinatal epigenetic marking at the RXRA promoter region in umbilical cord was inversely associated with offspring size–corrected BMC in childhood. The potential mechanistic and functional significance of this finding remains a subject for further investigation.

Inflammation, Telomere Length, and Grip Strength: A 10-year Longitudinal Study

Telomere attrition has been associated with age-related diseases, although causality is unclear and controversial; low-grade systemic inflammation (inflammaging) has also been implicated in age-related pathogenesis. Unpicking the relationship between aging, telomere length (TL), and inflammaging is hence essential to the understanding of aging and management of age-related diseases. This longitudinal study explored whether telomere attrition is a cause or consequence of aging and whether inflammaging explains some of the associations between TL and one marker of aging, grip strength. We studied 253 Hertfordshire Ageing Study participants at baseline and 10-year follow-up (mean age at baseline 67.1xa0years). Participants completed a health questionnaire and had blood samples collected for immune–endocrine and telomere analysis at both time points. Physical aging was characterized at follow-up using grip strength. Faster telomere attrition was associated with lower grip strength at follow-up (βxa0=xa00.98, pxa0=xa00.035). This association was completely attenuated when adjusted for inflammaging burden (pxa0=xa00.86) over the same period. Similarly, greater inflammaging burden was associated with lower grip strength at follow-up (e.g., interleukin [IL]-1β: βxa0=xa0−2.18, pxa0=xa00.001). However, these associations were maintained when adjusted for telomere attrition (IL-1β, pxa0=xa00.006). We present evidence that inflammaging may be driving telomere attrition and in part explains the associations that have previously been reported between TL and grip strength. Thus, biomarkers of physical aging, such as inflammaging, may require greater exploration. Further work is now indicated.

Type of milk feeding in infancy and health behaviours in adult life: findings from the Hertfordshire Cohort Study

A number of studies suggest that breast-feeding has beneficial effects on an individuals cardiovascular risk factors in adulthood, although the mechanisms involved are unknown. One possible explanation is that adults who were breastfed differ in their health behaviours. In a historical cohort, adult health behaviours were examined in relation to type of milk feeding in infancy. From 1931 to 1939, records were kept on all infants born in Hertfordshire, UK. Their type of milk feeding was summarised as breastfed only, breast and bottle-fed, or bottle-fed only. Information about adult health behaviours was collected from 3217 of these men and women when they were aged 59-73 years. Diet was assessed using an administered FFQ; the key dietary pattern was a prudent pattern that described compliance with healthy eating recommendations. Of the study population, 60 % of the men and women were breastfed, 31 % were breast and bottle-fed, and 9 % were bottle-fed. Type of milk feeding did not differ according to social class at birth, and was not related to social class attained in adult life. There were no differences in smoking status, alcohol intake or reported physical activity according to type of milk feeding, but there were differences in the participants dietary patterns. In a multivariate model that included sex and infant weight gain, there were independent associations between type of feeding and prudent diet scores in adult life (P= 0.009), such that higher scores were associated with having been breastfed. These data support experimental findings which suggest that early dietary exposures can have lifelong influences on food choice.

Lean mass and fat mass have differing associations with bone microarchitecture assessed by high resolution peripheral quantitative computed tomography in men and women from the Hertfordshire Cohort Study.

Understanding the effects of muscle and fat on bone is increasingly important in the optimisation of bone health. We explored relationships between bone microarchitecture and body composition in older men and women from the Hertfordshire Cohort Study. 175 men and 167 women aged 72-81 years were studied. High resolution peripheral quantitative computed tomography (HRpQCT) images (voxel size 82 μm) were acquired from the non-dominant distal radius and tibia with a Scanco XtremeCT scanner. Standard morphological analysis was performed for assessment of macrostructure, densitometry, cortical porosity and trabecular microarchitecture. Body composition was assessed using dual energy X-ray absorptiometry (DXA) (Lunar Prodigy Advanced). Lean mass index (LMI) was calculated as lean mass divided by height squared and fat mass index (FMI) as fat mass divided by height squared. The mean (standard deviation) age in men and women was 76 (3) years. In univariate analyses, tibial cortical area (p<0.01), cortical thickness (p<0.05) and trabecular number (p<0.01) were positively associated with LMI and FMI in both men and women. After mutual adjustment, relationships between cortical area and thickness were only maintained with LMI [tibial cortical area, β (95% confidence interval (CI)): men 6.99 (3.97,10.01), women 3.59 (1.81,5.38)] whereas trabecular number and density were associated with FMI. Interactions by sex were found, including for the relationships of LMI with cortical area and FMI with trabecular area in both the radius and tibia (p<0.05). In conclusion, LMI and FMI appeared to show independent relationships with bone microarchitecture. Further studies are required to confirm the direction of causality and explore the mechanisms underlying these tissue-specific associations.

Placental size at 19 weeks predicts offspring bone mass at birth: findings from the Southampton Women's Survey.

OBJECTIVESnIn this study we investigate the relationships between placental size and neonatal bone mass and body composition, in a population-based cohort.nnnSTUDY DESIGNn914 mother-neonate pairs were included. Placental dimensions were measured via ultrasound at 19 weeks gestation. Dual X-ray absorptiometry (DXA) was performed on the neonates within the first two weeks of life.nnnRESULTSnWe observed positive relationships between placental volume at 19 weeks, and neonatal bone area (BA; r = 0.26, p < 0.001), bone mineral content (BMC; r = 0.25, p < 0.001) and bone mineral density (BMD; r = 0.10, p = 0.001). Thus placental volume accounted for 6.25% and 1.2% of the variation in neonatal BMC and BMD respectively at birth. These associations remained after adjustment for maternal factors previously shown to be associated with neonatal bone mineral accrual (maternal height, smoking, walking speed in late pregnancy, serum 25(OH) vitamin D and triceps skinfold thickness).nnnCONCLUSIONSnWe found that placental volume at 19 weeks gestation was positively associated with neonatal bone size and mineral content. These relationships appeared independent of those maternal factors known to be associated with neonatal bone mass, consistent with notion that such maternal influences might act through modulation of aspects of placental function, e.g. utero-placental blood flow or maternal nutrient concentrations, rather than placental size itself. Low placental volume early in pregnancy may be a marker of a reduced postnatal skeletal size and increased risk of later fracture.