Agents intervening against delirium in the intensive care unit (AID-ICU) - Protocol for a randomised placebo-controlled trial of haloperidol in patients with delirium in the ICU

Background Delirium among patients in the intensive care unit (ICU) is a common condition associated with increased morbidity and mortality. Haloperidol is the most frequently used pharmacologic intervention, but its use is not supported by firm evidence. Therefore, we are conducting Agents Intervening against Delirium in the Intensive Care Unit (AID‐ICU) trial to assess the benefits and harms of haloperidol for the treatment of ICU‐acquired delirium. Methods AID‐ICU is an investigator‐initiated, pragmatic, international, randomised, blinded, parallel‐group, trial allocating adult ICU patients with manifest delirium 1:1 to haloperidol or placebo. Trial participants will receive intravenous 2.5 mg haloperidol three times daily or matching placebo (isotonic saline 0.9%) if they are delirious. If needed, a maximum of 20 mg/daily haloperidol/placebo is given. An escape protocol, not including haloperidol, is part of the trial protocol. The primary outcome is days alive out of the hospital within 90 days post‐randomisation. Secondary outcomes are number of days without delirium or coma, serious adverse reactions to haloperidol, usage of escape medication, number of days alive without mechanical ventilation; mortality, health‐related quality‐of‐life and cognitive function at 1‐year follow‐up. A sample size of 1000 patients is required to detect a 7‐day improvement or worsening of the mean days alive out of the hospital, type 1 error risk of 5% and power 90%. Perspective The AID‐ICU trial is based on gold standard methodology applied to a large sample of clinically representative patients and will provide pivotal high‐quality data on the benefits and harms of haloperidol for the treatment ICU‐acquired delirium

Divergent functional isoforms drive niche specialisation for nutrient acquisition and use in rumen microbiome

Many microbes in complex competitive environments share genes for acquiring and utilising nutrients, questioning whether niche specialisation exists and if so, how it is maintained. We investigated the genomic signatures of niche specialisation in the rumen microbiome, a highly competitive, anaerobic environment, with limited nutrient availability determined by the biomass consumed by the host. We generated individual metagenomic libraries from 14 cows fed an ad libitum diet of grass silage and calculated functional isoform diversity for each microbial gene identified. The animal replicates were used to calculate confidence intervals to test for differences in diversity of functional isoforms between microbes that may drive niche specialisation. We identified 153 genes with significant differences in functional isoform diversity between the two most abundant bacterial genera in the rumen (Prevotella and Clostridium). We found Prevotella possesses a more diverse range of isoforms capable of degrading hemicellulose, whereas Clostridium for cellulose. Furthermore, significant differences were observed in key metabolic processes indicating that isoform diversity plays an important role in maintaining their niche specialisation. The methods presented represent a novel approach for untangling complex interactions between microorganisms in natural environments and have resulted in an expanded catalogue of gene targets central to rumen cellulosic biomass degradation

Tuber shape and eye depth variation in a diploid family of Andean potatoes.

BACKGROUND: Tuber appearance is highly variable in the Andean cultivated potato germplasm. The diploid backcross mapping population ‘DMDD’ derived from the recently sequenced genome ‘DM’ represents a sample of the allelic variation for tuber shape and eye depth present in the Andean landraces. Here we evaluate the utility of morphological descriptors for tuber shape for identification of genetic loci responsible for the shape and eye depth variation. RESULTS: Subjective morphological descriptors and objective tuber length and width measurements were used for assessment of variation in tuber shape and eye depth. Phenotypic data obtained from three trials and male–female based genetic maps were used for quantitative trait locus (QTL) identification. Seven morphological tuber shapes were identified within the population. A continuous distribution of phenotypes was found using the ratio of tuber length to tuber width and a QTL was identified in the paternal map on chromosome 10. Using toPt-437059, the marker at the peak of this QTL, the seven tuber shapes were classified into two groups: cylindrical and non-cylindrical. In the first group, shapes classified as ‘compressed’, ‘round’, ‘oblong’, and ‘long-oblong’ mainly carried a marker allele originating from the male parent. The tubers in this group had deeper eyes, for which a strong QTL was found at the same location on chromosome 10 of the paternal map. The non-cylindrical tubers classified as ‘obovoid’, ‘elliptic’, and ‘elongated’ were in the second group, mostly lacking the marker allele originating from the male parent. The main QTL for shape and eye depth were located in the same genomic region as the previously mapped dominant genes for round tuber shape and eye depth. A number of candidate genes underlying the significant QTL markers for tuber shape and eye depth were identified. CONCLUSIONS: Utilization of a molecular marker at the shape and eye depth QTL enabled the reclassification of the variation in general tuber shape to two main groups. Quantitative measurement of the length and width at different parts of the tuber is recommended to accompany the morphological descriptor classification to correctly capture the shape variation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-015-0213-0) contains supplementary material, which is available to authorized users

Development of an ICU discharge instrument predicting psychological morbidity : a multinational study

PURPOSE: To develop an instrument for use at ICU discharge for prediction of psychological problems in ICU survivors. METHODS: Multinational, prospective cohort study in ten general ICUs in secondary and tertiary care hospitals in Sweden, Denmark and the Netherlands. Adult patients with an ICU stay ≥ 12 h were eligible for inclusion. Patients in need of neurointensive care, with documented cognitive impairment, unable to communicate in the local language, without a home address or with more than one limitation of therapy were excluded. Primary outcome was psychological morbidity 3 months after ICU discharge, defined as Hospital Anxiety and Depression Scale (HADS) subscale score ≥ 11 or Post-traumatic Stress Symptoms Checklist-14 (PTSS-14) part B score > 45. RESULTS: A total of 572 patients were included and 78% of patients alive at follow-up responded to questionnaires. Twenty percent were classified as having psychological problems post-ICU. Of 18 potential risk factors, four were included in the final prediction model after multivariable logistic regression analysis: symptoms of depression [odds ratio (OR) 1.29, 95% confidence interval (CI) 1.10-1.50], traumatic memories (OR 1.44, 95% CI 1.13-1.82), lack of social support (OR 3.28, 95% CI 1.47-7.32) and age (age-dependent OR, peak risk at age 49-65 years). The area under the receiver operating characteristics curve (AUC) for the instrument was 0.76 (95% CI 0.70-0.81). CONCLUSIONS: We developed an instrument to predict individual patients' risk for psychological problems 3 months post-ICU, http://www.imm.ki.se/biostatistics/calculators/psychmorb/ . The instrument can be used for triage of patients for psychological ICU follow-up. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov, NCT02679157