Biomarkers as diagnostic or prognostic indicators of delirium: examining the current evidence

Delirium is a substantial global health concern. Delirium can lead to longer hospital stays and increased healthcare costs. Effective detection and prevention of delirium is still a major challenge for health-care organisations globally. This is largely because the cause(s) of the condition are still unknown. There are multiple factors which may contribute to the aetiology of delirium and a range of neurobiological processes that may be associated with its pathophysiology. With this said, evidencing these processes is a significant challenge as there is a dearth of existing methods of identification. Recently, the use of biomarkers has become a popular method in the identification of delirium and its risk of development. The identification of biomarkers associated with delirium may provide insight into its pathophysiology and aid in diagnosis and management. However, there is a lack of research that has synthesised the diagnostic and prognostic value of biomarkers associated with delirium, and how they can be employed to improve patient outcomes. A systematic review by Dunne et al. 2021 was undertaken to explore this association of biomarkers and delirium. This commentary aims to critically appraise the methods used within the review by Dunne et al. (2021) and expand upon the findings in the context of clinical practice

Influence of iodide ingestion on nitrate metabolism and blood pressure following short-term dietary nitrate supplementation in healthy normotensive adults

Uptake of inorganic nitrate (NO3−) into the salivary circulation is a rate-limiting step for dietary NO3− metabolism in mammals. It has been suggested that salivary NO3− uptake occurs in competition with inorganic iodide (I−). Therefore, this study tested the hypothesis that I− supplementation would interfere with NO3− metabolism and blunt blood pressure reductions after dietary NO3− supplementation. Nine healthy adults (4 male, mean ± SD, age 20 ± 1 yr) reported to the laboratory for initial baseline assessment (control) and following six day supplementation periods with 140 mL·day−1 NO3−-rich beetroot juice (8.4 mmol NO3−·day−1) and 198 mg potassium gluconate·day−1 (nitrate), and 140 mL·day−1 NO3−-rich beetroot juice and 450 μg potassium iodide·day−1 (nitrate + iodide) in a randomized, cross-over experiment. Salivary [I−] was higher in the nitrate + iodide compared to the control and NIT trials (P 0.05). Systolic blood pressure was lower than control (112 ± 13 mmHg) in the nitrate (106 ± 13 mmHg) and nitrate + iodide (106 ± 11 mmHg) trials (P 0.05). In conclusion, co-ingesting NO3− and I− perturbed salivary NO3− uptake, but the increase in salivary and plasma [NO2−] and the lowering of blood pressure were similar compared to NO3− ingestion alone. Therefore, increased dietary I− intake, which is recommended in several countries worldwide as an initiative to offset hypothyroidism, does not appear to compromise the blood pressure reduction afforded by increased dietary NO3− intake

Visual Scan Paths and Recognition of Facial Identity in Autism Spectrum Disorder and Typical Development

Background: Previous research suggests that many individuals with autism spectrum disorder (ASD) have impaired facial identity recognition, and also exhibit abnormal visual scanning of faces. Here, two hypotheses accounting for an association between these observations were tested: i) better facial identity recognition is associated with increased gaze time on the Eye region; ii) better facial identity recognition is associated with increased eye-movements around the face. Methodology and Principal Findings: Eye-movements of 11 children with ASD and 11 age-matched typically developing (TD) controls were recorded whilst they viewed a series of faces, and then completed a two alternative forced-choice recognition memory test for the faces. Scores on the memory task were standardized according to age. In both groups, there was no evidence of an association between the proportion of time spent looking at the Eye region of faces and age-standardized recognition performance, thus the first hypothesis was rejected. However, the 'Dynamic Scanning Index' - which was incremented each time the participant saccaded into and out of one of the core-feature interest areas - was strongly asso ciated with age-standardized face recognition scores in both groups, even after controlling for various other potential predictors of performance. Conclusions and Significance: In support of the second hypothesis, results suggested that increased saccading between core-features was associated with more accurate face recognition ability, both in typical development and ASD. Causal directions of this relationship remain undetermined.10 page(s

Spondylarthropathies (including psoriatic arthritis): 244. Validity of Colour Doppler and Spectral Doppler Ultrasound of Sacroilicac Joints Againts Physical Examination as Gold Standard

Background: Sacroiliac joints (SJ) involvement is a distinctive and charasteristic feature of Spondyloarthritis (SpA) and x-ray is the test routinely used to make a diagnosis. However, x-ray reveals late structural damage but cannot detect active inflammation. The objective of this study was to assess the validity of Doppler ultrasound in SJ. Methods: Prospective blinded and controlled study of SJ, in which three populations were compared. We studied 106 consecutive cases, who were divided into three groups: a) 53 patients diagnosed with SpA who had inflammatory lumbar and gluteal pain assessed by a rheumatologist; b) 26 patients diagnosed with SpA who didn't have SJ tenderness and had normal physical examination; c) control group of 27 subjects (healthy subjetcs or with mechanical lumbar pain). All patients included that were diagnosed with SpA met almost the European Spondyloarthropathy Study Group (ESSG) classification criteria. Physical examination of the SJ included: sacral sulcus tenderness, iliac gapping, iliac compression, midline sacral thrust test, Gaenslen's test, and Patrick s test were used as gold standard. Both SJ were examined with Doppler ultrasound (General Electric Logiq 9, Wauwatosa WI, USA) fitted with a 9-14 Mhz lineal probe. The ultrasonographer was blinded to clinical data. Doppler in SJ was assessed as positive when both Doppler colour and resistance index (RI) < 0.75 within the SJ area were present. Statistical analysis was performed estimating sensitivity and specificity against gold standard. The Kappa correlation coefficient was used for reliability study. Results: 106 cases (53 female, 55 male; mean age 36 10 years) were studied. There were no statistical differences between groups related to age or sex. Physical examination of SJ was positive in 38 patients (59 sacroiliac joints). US detected Doppler signal within SJ in 37 patients (58 SJ): 33 of them were symptomatic SpA (52 SJ), one of them were asymptomatic SpA (1 SJ) and one was a healthy control (1 SJ). The accuracy of US when compared to clinical data as gold standard at subject level in the overall group was: sensitivity of 68.6% and specificity of 85.7%, positive predictive value of 70.5% and negative predictive value of 84.5%. A positive likelihood ratio of 4.8, a negative likelihood ratio of 0.36 and a kappa coefficient of 0.55 were achieved. Conclusions: Doppler US of SJ seems to be a valid method to detect active SJ inflammation. Disclosure statement: The authors have declared no conflicts of interes

Influence of iodide ingestion on nitrate metabolism and blood pressure following short-term dietary nitrate supplementation in healthy normotensive adults

This paper was accepted for publication in the journal Nitric Oxide and the definitive published version is available at http://dx.doi.org/10.1016/j.niox.2016.12.008Uptake of inorganic nitrate (NO3−) into the salivary circulation is a rate-limiting step for dietary NO3− metabolism in mammals. It has been suggested that salivary NO3− uptake occurs in competition with inorganic iodide (I−). Therefore, this study tested the hypothesis that I− supplementation would interfere with NO3− metabolism and blunt blood pressure reductions after dietary NO3− supplementation. Nine healthy adults (4 male, mean ± SD, age 20 ± 1 yr) reported to the laboratory for initial baseline assessment (control) and following six day supplementation periods with 140 mL·day−1 NO3−-rich beetroot juice (8.4 mmol NO3−·day−1) and 198 mg potassium gluconate·day−1 (nitrate), and 140 mL·day−1 NO3−-rich beetroot juice and 450 μg potassium iodide·day−1 (nitrate + iodide) in a randomized, cross-over experiment. Salivary [I−] was higher in the nitrate + iodide compared to the control and NIT trials (P < 0.05). Salivary and plasma [NO3−] and [NO2−] were higher in the nitrate and nitrate + iodide trials compared to the control trial (P < 0.05). Plasma [NO3−] was higher (474 ± 127 vs. 438 ± 117 μM) and the salivary-plasma [NO3−] ratio was lower (14 ± 6 vs. 20 ± 6 μM), indicative of a lower salivary NO3− uptake, in the nitrate + iodide trial compared to the nitrate trial (P < 0.05). Plasma and salivary [NO2−] were not different between the nitrate and nitrate + iodide trials (P > 0.05). Systolic blood pressure was lower than control (112 ± 13 mmHg) in the nitrate (106 ± 13 mmHg) and nitrate + iodide (106 ± 11 mmHg) trials (P < 0.05), with no differences between the nitrate and nitrate + iodide trials (P > 0.05). In conclusion, co-ingesting NO3− and I− perturbed salivary NO3− uptake, but the increase in salivary and plasma [NO2−] and the lowering of blood pressure were similar compared to NO3− ingestion alone. Therefore, increased dietary I− intake, which is recommended in several countries worldwide as an initiative to offset hypothyroidism, does not appear to compromise the blood pressure reduction afforded by increased dietary NO3− intake

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

The Correlation of Topographically-Derived Relative Wetness with Terrestrial Mollusk Presence and Abundance

Many species of terrestrial mollusks are small and difficult to find, with poorly known ranges and habitat preferences. Because desiccation is a primary cause of mortality for many terrestrial mollusks, incorporating wetness as a habitat variable may improve survey results for different species. We compared presence and abundance data from terrestrial mollusk surveys in Tillamook Resource Area to two measures of relative wetness: topographic wetness index (TWI) and geomorphic features (landslides, debris-flow channels, etc.). Hurdle Model regression revealed a positive correlation between increased TWI and likelihood of presence or abundance for four species, and a negative correlation for six species. Overall species diversity and total mollusk count were negatively correlated with increased TWI, but the effect size was small (p = 0.02, R2= -0.03). Our Kruskal-Wallis Analysis of Variance of TWI between species was significant (p \u3c 0.001), indicating terrestrial mollusks occupy significantly different wetness regimes – but this relationship was driven entirely by the wetness specialization of Hemphillia glandulosa. Our chi-square analysis of topographic features found significant preferences of different species for different topographic types, which correlated loosely but not precisely to the preferences indicated by TWI. These results show that altering current terrestrial mollusk survey protocol to include geomorphic features, which are simpler and less time-intensive than calculating TWI, would increase detection likelihood of certain species, including Hemphillia glandulosa, a species protected under the Survey and Manage guidelines of the Northwest Forest Plan

Supplementary Data Terrestrial Mollusk Location and Species Count

Supporting data in csv table format.Many species of terrestrial mollusks are small and difficult to find, with poorly known ranges and habitat preferences. Because desiccation is a primary cause of mortality for many terrestrial mollusks, incorporating wetness as a habitat variable may improve survey results for different species of terrestrial mollusks. We compared presence and abundance data from terrestrial mollusk surveys in Tillamook Resource Area to two measures of relative wetness: topographic wetness index (TWI) and geomorphic features (landslides, debris-flow channels, etc.). Hurdle Model regression revealed a positive correlation between increased TWI and likelihood of presence or abundance for five species, and a negative correlation for four species. Overall species diversity and total mollusk count were negatively correlated with increased TWI, but the effect size was small (p = 0.02, R2 = -0.03). Our Kruskal-Wallis Analysis of Variance of TWI between species was significant (p<0.001), indicating terrestrial mollusks occupy significantly different wetness regimes - but this relationship was driven entirely by the wetness specialization of Hemphillia glandulosa. Our chi square analysis of topographic features found significant preferences of different species for different topographic types, which correlated loosely but not precisely to the preferences indicated by TWI. These results show that altering current terrestrial mollusk survey protocol to include geomorphic features (which are simpler and less time-intensive than calculating TWI) would increase detection likelihood of certain species, including Hemphillia glandulosa, a species protected under the Survey and Manage guidelines of the Northwest Forest Plan

Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data

Abstract: Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers