Culture Positivity of CVCs Used for TPN: Investigation of an Association with Catheter-Related Infection and Comparison of Causative Organisms between ICU and Non-ICU CVCs

A relationship between central venous catheter (CVC) tip colonisation and catheter-related blood-stream infection (CRBSI) has been suggested. We examined culture positivity of CVC tips (colonised and infected CVCs) in a total parenteral nutrition (TPN) population. Our aims were to define the relationship between culture positivity and CRBSI, and to compare causative organisms between culture positive and CRBSI CVCS, and between ward and ICU CVCs. All patients receiving TPN via non-tunnelled CVCs during the study (1997-2009) were included. All CVC tips were analysed. Data were collated contemporaneously. A TPN audit committee determined whether CVC tip culture positivity reflected colonisation/CRBSI using CDC criteria. 1,392 patients received TPN via 2,565 CVCs over 15,397 CVC days. 25.4% of CVCs tips were culture positive, of these 32% developed CRBSI. There was a nonsignificant trend of higher Gram negative Bacilli isolation in ICU CVCs ( P = 0 . 1 ) , ward CVCs were associated with higher rates of staphylococcal isolation ( P = 0 . 0 1 ) . A similar pattern of organisms were cultured from CRBSI and culture positive CVCs. The consistent relationship between CRBSI and culture positive CVCs, and similar pattern of causative organisms further supports an aetiological relationship between culture positive CVC tips and CRBSI, supporting the contention that CVC culture-positivity may be a useful surrogate marker for CRBSI rates

Is Long-Term Exposure to Ambient Air Pollution a Risk Factor for Parkinson’s Disease.

Objectives This paper links prescriptions data for the Northern Ireland population with data from the Northern Ireland Longitudinal Study and localized ambient air pollution data from 2002 onwards to estimate the association between long-term exposure to ambient air pollutant from fine particulates (PM2.5) and Parkinson’s Disease (PD). Approach Cox Proportional Hazards models are used to examine the impact of air pollution on PD, first unconditionally, and then conditioning on a rich set of observable individual, family and contextual characteristics. Long-term exposure to PM2.5 is defined as exposure averaged over the previous 5 years. Onset of PD is proxied by first receipt of a prescription for PD medication.  Estimates are presented in the form of hazard ratios for the effect of long-term PM2.5 exposure on the risk of PD onset. Results There is a non-trivial magnitude and statistically significant unconditional association between long-term exposure to ambient PM2.5 pollution and receiving a prescription for PD, with those exposed to higher levels of pollution more likely to receive a prescription for PD. This estimated association disappears (becomes insignificantly different from zero), however, when the model accounts for confounding variables at household, individual and geographical levels. Conclusions This study contributes to an emerging literature examining the association between ambient PM2.5 pollution and onset of PD. Despite finding an unconditional association, we find no evidence for an association once individual, family and contextual characteristics are controlled for, at least in the relatively low-pollution context of Northern Ireland

Long-term Exposure to Ambient PM2.5 and Self-Reported Health: Evidence from Longitudinally-linked Census Data.

Objectives This paper estimates associations between long-term exposure to ambient particulate air pollution and 13 self-reported health outcomes including poor general health, chronic illness, experiencing long-running difficulties with breathing, and experiencing frequent periods of confusion or memory loss. It examines the extent to which these associations are explained by confounding factors. Approach Longitudinally-linked Census data from the Northern Ireland Longitudinal Study linked to data on annual average particulate (PM2.5) concentrations at the 1km grid-square level over the period 2002-2010, exploiting complete residential histories, are used. The paper controls for potentially confounding factors at the neighbourhood, household and individual level, including for prior health, in a multivariate regression framework. Robustness to the presence of remaining unobserved confounders is assessed in two extensions, first by assuming selection on unobservables is proportional to selection on observables, and second through inclusion of an extensive set of fixed effects in the model. Results There are strong statistical associations between long-term exposure to ambient particulate pollution and all 13 health outcomes measured by the 2011 Northern Ireland Census. Most of these estimated associations survive conditioning on an extensive set of observable controls. Of these, however, only two associations – with chronic illness and with long-running breathing difficulties, where we might expect the strongest causal effects – survive further analysis designed to elicit robustness to selection on unobservables. The estimated magnitudes of these remaining effects are non-trivial. For example, a 5 µg/m3 difference in particulate exposure averaged over 9 years has a similar magnitude effect on the probability of reporting long-running breathing difficulties as the difference between those aged in their 20s and those in their 40s. Conclusions This study provides evidence of substantial effects of long-term exposure to ambient particulates on the probabilities of experiencing chronic illness and long-running breathing difficulties. These are qualitatively robust to both observed and unobserved confounders. Associations between particulate exposure and other health outcomes in the study are shown to reflect confounders

Exposure to PM 2.5 and Birth Outcomes: Evidence from a Population-wide Database.

This paper links localised annual average ambient air pollution data to a population database of births in Northern Ireland between 2011 and 2017 to investigate the relationship between particulate matter (PM) 2.5 exposure during pregnancy and a range of birth outcomes, with a focus on birth weight. Linear regression analysis is used to estimate the effect of exposure to PM 2.5 during pregnancy on commonly studied markers of infant health (birth weight, preterm birth), less commonly studied markers such as Apgar scores, and markers of placental health which potentially represent a mechanism through which pollution might negatively affect newborns. In addition to maternal characteristics and weather conditions, detailed adjustment is made for area of residence. Moreover, comparisons of birth outcomes are drawn amongst siblings born at different times and subject to different levels of in utero exposure, permitting adjustment for mother-specific factors common to siblings. Most birth outcomes exhibit a strong unadjusted association with PM 2.5 exposure that conforms with expectations. For birth weight, the negative effect of PM 2.5 weakens slightly after adjusting for differences in maternal characteristics and weather, but weakens much further after adjusting additionally for area of residence. After adjustment, being born to mothers in the middling (6-10 micrograms per cubic metre) and highest (10-16 micrograms per cubic metre) categories of exposure is associated with a 12 gram and 32 gram reduction in mean birth weight, respectively, compared to being born into the lowest (3-6 micrograms per cubic metre) category. However, after adjusting additionally for mother-specific factors, these effects become statistically no different from zero. This holds for other outcomes, including measures of placental health. We find little evidence that exposure to PM 2.5 is related to worse infant health once we adjust as fully as possible for omitted variable bias. We conclude that the association between PM 2.5 and birth outcomes in this population at least partly reflects unmeasured characteristics of families

Variation in Treatment of Patients With Inflammatory Bowel Diseases at Major Referral Centers in the United States

We performed a prospective study of patients with inflammatory bowel diseases to examine variations in treatment among medical centers. In a prospective cohort study of 1659 patients with CD and 946 patients with UC seen at 7 high-volume referral centers, we collected data on demographics, disease characteristic, and medical and surgical treatments. We used logistic regression to determine differences in treatment among centers, controlling for potential confounders. We found significant variations among centers in treatment of CD with immunomodulators (odds ratio [OR], 3.34; 95% confidence interval [CI], 2.09 – 5.32) but not anti-tumor necrosis factor agents (OR, 1.64; 95% CI, 0.97 – 2.77). There was less variation in treatment of UC; we found no difference in use of immunomodulators (OR,1.83 95% CI, 1.00 – 3.36) or anti-TNF therapy (OR, 0.81; 95% CI, 0.40 – 1.65). Development and implementation of evidence-based standards of care for IBD may help reduce variation and improve outcomes

Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism.

Fucosyltransferase 2 (FUT2) is an enzyme that is responsible for the synthesis of the H antigen in body fluids and on the intestinal mucosa. The H antigen is an oligosaccharide moiety that acts as both an attachment site and carbon source for intestinal bacteria. Non-secretors, who are homozygous for the loss-of-function alleles of FUT2 gene (sese), have increased susceptibility to Crohn's disease (CD). To characterize the effect of FUT2 polymorphism on the mucosal ecosystem, we profiled the microbiome, meta-proteome and meta-metabolome of 75 endoscopic lavage samples from the cecum and sigmoid of 39 healthy subjects (12 SeSe, 18 Sese and 9 sese). Imputed metagenomic analysis revealed perturbations of energy metabolism in the microbiome of non-secretor and heterozygote individuals, notably the enrichment of carbohydrate and lipid metabolism, cofactor and vitamin metabolism and glycan biosynthesis and metabolism-related pathways, and the depletion of amino-acid biosynthesis and metabolism. Similar changes were observed in mice bearing the FUT2(-/-) genotype. Metabolomic analysis of human specimens revealed concordant as well as novel changes in the levels of several metabolites. Human metaproteomic analysis indicated that these functional changes were accompanied by sub-clinical levels of inflammation in the local intestinal mucosa. Therefore, the colonic microbiota of non-secretors is altered at both the compositional and functional levels, affecting the host mucosal state and potentially explaining the association of FUT2 genotype and CD susceptibility

Wireless aquatic navigator for detection and analysis (WANDA)

The cost of monitoring and detecting pollutants in natural waters is of major concern. Current and forthcoming bodies of legislation will continue to drive demand for spatial and selective monitoring of our environment, as the focus increasingly moves towards effective enforcement of legislation through detection of events, and unambiguous identification of perpetrators. However, these monitoring demands are not being met due to the infrastructure and maintenance costs of conventional sensing models. Advanced autonomous platforms capable of performing complex analytical measurements at remote locations still require individual power, wireless communication, processor and electronic transducer units, along with regular maintenance visits. Hence the cost base for these systems is prohibitively high, and the spatial density and frequency of measurements are insufficient to meet requirements. In this paper we present a more cost effective approach for water quality monitoring using a low cost mobile sensing/communications platform together with very low cost stand-alone ‘satellite’ indicator stations that have an integrated colorimetric sensing material. The mobile platform is equipped with a wireless video camera that is used to interrogate each station to harvest information about the water quality. In simulation experiments, the first cycle of measurements is carried out to identify a ‘normal’ condition followed by a second cycle during which the platform successfully detected and communicated the presence of a chemical contaminant that had been localised at one of the satellite stations

A screen of Crohn's disease-associated microbial metabolites identifies ascorbate as a novel metabolic inhibitor of activated human T cells.

Microbial metabolites are an emerging class of mediators influencing CD4+ T-cell function. To advance the understanding of direct causal microbial factors contributing to Crohn's disease, we screened 139 predicted Crohn's disease-associated microbial metabolites for their bioactivity on human CD4+ T-cell functions induced by disease-associated T helper 17 (Th17) polarizing conditions. We observed 15 metabolites with CD4+ T-cell bioactivity, 3 previously reported, and 12 unprecedented. A deeper investigation of the microbe-derived metabolite, ascorbate, revealed its selective inhibition on activated human CD4+ effector T cells, including IL-17A-, IL-4-, and IFNγ-producing cells. Mechanistic assessment suggested the apoptosis of activated human CD4+ T cells associated with selective inhibition of energy metabolism. These findings suggest a substantial rate of relevant T-cell bioactivity among Crohn's disease-associated microbial metabolites, and evidence for novel modes of bioactivity, including targeting of T-cell energy metabolism

IBD-Associated TL1A Gene (TNFSF15) Haplotypes Determine Increased Expression of TL1A Protein

BACKGROUND: The recently identified member of the TNF superfamily TL1A (TNFSF15) increases IFN-gamma production by T cells in peripheral and mucosal CCR9+ T cells. TL1A and its receptor DR3 are up-regulated during chronic intestinal inflammation in ulcerative colitis and Crohn's disease (CD). TL1A gene haplotypes increase CD susceptibility in Japanese, European, and US cohorts. METHODOLOGY AND PRINCIPAL FINDINGS: Here we report that the presence of TL1A gene haplotype B increases risk in Jewish CD patients with antibody titers for the E. coli outer membrane porin C (OmpC+) (Haplotype B frequency in Jewish CD patients: 24.9% for OmpC negative and 41.9% for OmpC positive patients, respectively, P< or =0.001). CD14+ monocytes isolated from Jewish OmpC+ patients homozygous for TL1A gene haplotype B express higher levels of TL1A in response to FcgammaR stimulation, a known inducing pathway of TL1A, as measured by ELISA. Furthermore, the membrane expression of TL1A is increased on peripheral monocytes from Jewish but not non-Jewish CD patients with the risk haplotype. CONCLUSIONS AND SIGNIFICANCE: These findings suggest that TL1A gene variation exacerbates induction of TL1A in response to FcgammaR stimulation in Jewish CD patients and this may lead to chronic intestinal inflammation via overwhelming T cell responses. Thus, TL1A may provide an important target for therapeutic intervention in this subgroup of IBD patients