Sugar and spike: not so nice.
Ontology highlight
ABSTRACT:
SUBMITTER: McKenzie SE
PROVIDER: S-EPMC8529940 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundHyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU).MethodsWe conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation - Survival Using Glucose Algorithm Regulation) study.ResultsWe included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83-1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5-8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44-0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78-1.28; mixed ICU: RR 0.99, 95% CI 0.86-1.12). The different targets of intensive insulin therapy (glucose level < or = 6.1 mmol/L v. < or = 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia.InterpretationIntensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU.
| S-EPMC2665940 | biostudies-literature
Project description:INTRODUCTION: There is no information on the uptake of Intensive Insulin Therapy (IIT) before the Normoglycemia in Intensive Care Evaluation and Surviving Using Glucose Algorithm Regulation (NICE-SUGAR) trial in Australia and New Zealand (ANZ) and on the bi-national response to the trial, yet such data would provide important information on the evolution of ANZ practice in this field. We aimed to study ANZ glycaemic control before and after the publication of the results of the NICE-SUGAR trial. METHODS: We analysed glucose control in critically ill patients across Australia and New Zealand during a two-year period before and after the publication of the NICE-SUGAR study. We used the mean first day glucose (Glu1) (a validated surrogate of ICU glucose control) to define practice. The implementation of an IIT protocol was presumed if the median of Glu? measurements was <6.44 mmol/L for a given ICU. Hypoglycaemia was categorised as severe (glucose ?2.2 mmol/L) or moderate (glucose ?3.9 mmol/L). RESULTS: We studied 49 ICUs and 176,505 patients. No ICU practiced IIT before or after NICE-SUGAR. Overall, Glu1 increased from 7.96 (2.95) mmol/L to 8.03 (2.92) mmol/L (P <0.0001) after NICE-SUGAR. Similar increases were noted in all patient subgroups studied (surgical, medical, insulin dependent diabetes mellitus, ICU stay >48/<48 hours). The rate of severe and moderate hypoglycaemia before and after NICE-SUGAR study were 0.59% vs. 0.55% (P =0.33) and 6.62% vs. 5.68% (P <0.0001), respectively. Both crude and adjusted mortalities declined over the study period. CONCLUSIONS: IIT had not been adopted in ANZ before the NICE-SUGAR study and glycaemic control corresponded to that delivered in the control arm of NICE-SUGAR trial. There were only minor changes in practice after the trial toward looser glycaemic control. The rate of moderate hypoglycaemia and mortality decreased along with such changes.
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Project description:Mammalian chromatin is dynamic and contains structural information that leads to transcriptional regulation of genes by recruiting transcription factors and altering nucleosome positioning. Here, we describe open chromatin mapping using Nicking Enzyme assisted sequencing (NicE-seq) for integrative epigenomic analysis. NicE-seq captures open chromatin sites in both fixed and native cells and reveals the genomic location of open chromatin sites (OCS) and transcription factor occupancy at single nucleotide resolution, with as few as 250 HCT116 cells. In HCT116 cells a large percentage of the OCS were coincident with DHS (DNaseI hypersensitive site) and ATAC-seq sites. OCSs correlated well with RNA pol II occupancy and transcriptionally active chromatin marks, while displaying a pattern contrasting to CpG methylation. ChIP CTCF peaks common to OCS and DHS displayed a strong correlation with H3K4me3 and H3K27ac marks. Further peaks unique to OCS and ChIP CTCF peaks also correlated strongly with H3K4me3, H3K27ac and higher transcription. Similar results were also obtained for Max and Sp1 transcription factors. Using NicE-seq we have demonstrated that HCT116 cells, treated with anti cancer drug decitabine, displayed time dependent accumulation of OCS coinciding with hypomethylation of the genome, particularly in SINE and satellite repetitive DNA. Differentially methylated regions (DMRs) were more pronounced in promoters, 5’UTR, CpG islands and exons. In summary, sequence specificity offered by a nicking enzyme allows a means to study open chromatin structure and hypomethylation of genomes, revealing the open chromatin landscape in cellular context.
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Project description:National Institute for Health and Clinical Excellence (NICE) clinical guidelines and subsequent NICE issued 'recommendation reminders' advocate discontinuing two fertility procedures and caesarean sections in women with hepatitis. We assess whether NICE guidance in 2004 and recommendation reminders were associated with a change in the rate of clinical procedures performed.Routine inpatient Hospital Episode Statistics (HES) data were extracted from the HES database for 1st April 1998 to 31st March 2010 using OPCS procedure codes for varicocele operations in infertile men, endometrial biopsies in infertile women and caesarean sections in women with hepatitis B or C. We used Joinpoint regression to identify points in time when the trend in procedure rates changed markedly, to identify any influence of the release of NICE guidance.Between 1998-2010, planned caesarean sections in women with and without hepatitis B or C increased yearly (annual percentage change (APC) 4.9%, 95% CI 2.1% to 7.7%) in women with hepatitis, compared with women without (APC 4.0% [95% CI 2.7% to 5.3%] up to 2001, APC -0.6% [95% CI -2.8% to 1.8%] up to 2004 and 1.3% [95% CI 0.8% to 1.8%] up to 2010). In infertile women under 40 years of age, endometrial biopsies for investigation of infertility increased, APC 6.0% (95% CI 3.6% to 8.4%) up to 2003, APC 1.5% (95% CI -4.3% to 7.7%) to 2007 followed by APC 12.8% (95% CI 1.0% to 26.0%) to 2010. Varicocele procedures remained relatively static between 1998 and 2010 (APC -0.5%, 95% CI -2.3% to 1.3%).There was no decline in use of the three studied procedures, contrary to NICE guidance, and no change in uptake associated with the timing of NICE guidance or recommendation reminders. 'Do not do' recommendation reminders may be ineffective at improving clinical practice or achieving disinvestment.
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Project description:Open chromatin profiling integrates information across diverse regulatory elements to reveal the transcriptionally active genome. Tn5 transposase and DNase I sequencing-based methods prefer native or high cell numbers. Here, we describe NicE-seq (nicking enzyme assisted sequencing) for high-resolution open chromatin profiling on both native and formaldehyde-fixed cells. NicE-seq captures and reveals open chromatin sites (OCSs) and transcription factor occupancy at single nucleotide resolution, coincident with DNase hypersensitive and ATAC-seq sites at a low sequencing burden. OCSs correlate with RNA polymerase II occupancy and active chromatin marks, while displaying a contrasting pattern to CpG methylation. Decitabine-mediated hypomethylation of HCT116 displays higher numbers of OCSs.
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Project description:The syntactic organization of incidentally presented word pairs may affect behavior by providing actors with implicit propositions about how to behave. In Experiment 1, participants who had already played turns of a mixed-motive game were less cooperative after an explicit propositional suggestion that they had been nice in prior turns but were more cooperative after the suggestion that they should be nice in upcoming turns. In three subsequent experiments, implicit priming with the phrase nice act produced greater levels of defection, implying that actors responded to the implicit suggestion that they had been sufficiently nice already. In contrast, act nice produced greater levels of cooperation, implying that actors responded to the implicit suggestion that they should try to be nicer in upcoming turns. These effects occurred outside of awareness and disappeared when the interval between the words was long and when behavior was measured after a delay.
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