Diagnostic Overshadowing and Other Challenges Involved in the Diagnostic Process of Patients with Mental Illness Who Present in Emergency Departments with Physical Symptoms – A Qualitative Study

We conducted a qualitative study in the Emergency Departments (EDs) of four hospitals in order to investigate the perceived scope and causes of ‘diagnostic overshadowing’ – the misattribution of physical symptoms to mental illness – and other challenges involved in the diagnostic process of people with mental illness who present in EDs with physical symptoms. Eighteen doctors and twenty-one nurses working in EDs and psychiatric liaisons teams in four general hospitals in the UK were interviewed. Interviewees were asked about cases in which mental illness interfered with diagnosis of physical problems and about other aspects of the diagnostic process. Interviews were transcribed and analysed thematically. Interviewees reported various scenarios in which mental illness or factors related to it led to misdiagnosis or delayed treatment with various degrees of seriousness. Direct factors which may lead to misattribution in this regard are complex presentations or aspects related to poor communication or challenging behaviour of the patient. Background factors are the crowded nature of the ED environment, time pressures and targets and stigmatising attitudes held by a minority of staff. The existence of psychiatric liaison team covering the ED twenty-four hours a day, seven days a week, can help reduce the risk of misdiagnosis of people with mental illness who present with physical symptoms. However, procedures used by emergency and psychiatric liaison staff require fuller operationalization to reduce disagreement over where responsibilities lie.     

Validation of a Consensus Method for Identifying Delirium from Hospital Records

Background

Delirium is increasingly considered to be an important determinant of trajectories of cognitive decline. Therefore, analyses of existing cohort studies measuring cognitive outcomes could benefit from methods to ascertain a retrospective delirium diagnosis. This study aimed to develop and validate such a method for delirium detection using routine medical records in UK and Ireland.

Methods

A point prevalence study of delirium provided the reference-standard ratings for delirium diagnosis. Blinded to study results, clinical vignettes were compiled from participants'' medical records in a standardised manner, describing any relevant delirium symptoms recorded in the whole case record for the period leading up to case-ascertainment. An expert panel rated each vignette as unlikely, possible, or probable delirium and disagreements were resolved by consensus.

Results

From 95 case records, 424 vignettes were abstracted by 5 trained clinicians. There were 29 delirium cases according to the reference standard. Median age of subjects was 76.6 years (interquartile range 54.6 to 82.5). Against the original study DSM-IV diagnosis, the chart abstraction method gave a positive likelihood ratio (LR) of 7.8 (95% CI 5.7–12.0) and the negative LR of 0.45 (95% CI 0.40–0.47) for probable delirium (sensitivity 0.58 (95% CI 0.53–0.62); specificity 0.93 (95% CI 0.90–0.95); AUC 0.86 (95% CI 0.82–0.89)). The method diagnosed possible delirium with positive LR 3.5 (95% CI 2.9–4.3) and negative LR 0.15 (95% CI 0.11–0.21) (sensitivity 0.89 (95% CI 0.85–0.91); specificity 0.75 (95% CI 0.71–0.79); AUC 0.86 (95% CI 0.80–0.89)).

Conclusions

This chart abstraction method can retrospectively diagnose delirium in hospitalised patients with good accuracy. This has potential for retrospectively identifying delirium in cohort studies where routine medical records are available. This example of record linkage between hospitalisations and epidemiological data may lead to further insights into the inter-relationship between acute illness, as an exposure, for a range of chronic health outcomes.     

Dietary Habits in Patients with Ischemic Stroke: A Case-Control Study

Background and Aims

Diet appears to have some role in stroke development. The objective of our study was to describe the dietary habits in patients admitted with acute ischemic stroke and compare selected dietary components with healthy controls. Adherence to healthy diet behaviors was also assessed.

Methods

A case-control study of consecutive patients with acute ischemic stroke admitted to the Neurology Department of Hospital del Mar from 2007 to 2010. Patients were matched by age and sex with control subjects. A previously validated nutritional survey was administered to patients and controls. Demographic data, vascular risk factors, caloric intake and dietary nutrients were evaluated. Intention to follow a healthy diet was also assessed in both groups.

Results

A total of 300 acute ischemic stroke patients and 300 controls with evaluation of dietary habits. No differences were observed in vascular risk factors, except smoking habit, diabetes and ischemic heart disease. Stroke patients reported a higher caloric intake: 2444.8(1736.8–3244.5) vs 2208.7(1753.1–2860.7) Kcal, p = 0.001. After adjusting for energy intake, patients had higher intake of proteins (p<0.001; OR 1.02), total cholesterol (p = 0.001; OR 1.04), and breaded foods (p = 0.001; OR 1.94) and lower consumption of probiotic yogurt (p = 0.002; OR 0.88). Compared to patients, control participants indicated greater intention to eat vegetables (p = 0.002; OR 1.5) and whole foods (p = 0.000; OR 2.4) and reduce their intake of salt (p = 0.002; OR 1.7), fat (p = 0.000; OR 3.7) and sweets (p = 0.004; OR 1.7) than patients.

Conclusion

We observed different dietary patterns between stroke patients and controls. Stroke patients have a higher caloric intake and are less concerned about maintaining healthy nutritional habits.     

Enterovirus71 (EV71) Utilise Host microRNAs to Mediate Host Immune System Enhancing Survival during Infection

Hand, Foot and Mouth Disease (HFMD) is a self-limiting viral disease that mainly affects infants and children. In contrast with other HFMD causing enteroviruses, Enterovirus71 (EV71) has commonly been associated with severe clinical manifestation leading to death. Currently, due to a lack in understanding of EV71 pathogenesis, there is no antiviral therapeutics for the treatment of HFMD patients. Therefore the need to better understand the mechanism of EV71 pathogenesis is warranted. We have previously reported a human colorectal adenocarcinoma cell line (HT29) based model to study the pathogenesis of EV71. Using this system, we showed that knockdown of DGCR8, an essential cofactor for microRNAs biogenesis resulted in a reduction of EV71 replication. We also demonstrated that there are miRNAs changes during EV71 pathogenesis and EV71 utilise host miRNAs to attenuate antiviral pathways during infection. Together, data from this study provide critical information on the role of miRNAs during EV71 infection.     

Influence of Hepatitis C Virus and IL28B Genotypes on Liver Stiffness

Objective

Liver fibrosis has been associated with hepatitis C virus (HCV) genotype and genetic variation near the interleukin 28B (IL28B) gene, but the relative contribution is unknown. We aimed to investigate the relation between HCV genotypes, IL28B and development of liver stiffness.

Patients and Methods

This cross-sectional study consists of 369 patients with chronic hepatitis C (CHC). Liver stiffness was evaluated using transient elastograhy (TE). Factors associated with development of liver fibrosis were identified by logistic regression analysis.

Results

We identified 369 patients with CHC. 235 were male, 297 Caucasians, and 223 had been exposed to HCV through intravenous drug use. The overall median TE value was 7.4 kPa (interquartile range (IQR) 5.7–12.1). HCV replication was enhanced in patients carrying the IL28B CC genotype compared to TT and TC (5.8 vs. 5.4 log₁₀ IU/mL, p = 0.03). Patients infected with HCV genotype 3 had significantly higher TE values (8.2 kPa; IQR, 5.9–14.5) compared to genotype 1 (6.9 kPa; IQR, 5.4–10.9) and 2 (6.7 kPa; IQR, 4.9–8.8) (p = 0.02). Within patients with genotype 3, IL28B CC genotype had the highest TE values (p = 0.04). However, in multivariate logistic regression, using various cut-off values for fibrosis and cirrhosis, only increasing age (odds ratio (OR) 1.09 (95% confidence interval (CI), 1.05–1.14 per year increment)), ALT (OR 1.01 (95% CI, 1.002–1.011), per unit increment) and HCV genotype 3 compared to genotype 1 (OR 2.40 (95% CI, 1.19–4.81), were consistently associated with cirrhosis (TE>17.1 kPa).

Conclusions

Age, ALT and infection with HCV genotype 3 were associated with cirrhosis assessed by TE. However, IL28B genotype was not an independent predictor of fibrosis in our study.     

Widespread desert affiliation of trebouxiophycean algae (Trebouxiophyceae,Chlorophyta) including discovery of three new desert genera

Unlike most other green algae, trebouxiophyceans are predominantly aerophytic and contain many symbiotic representatives. In recent years, a number of new terrestrial trebouxiophycean taxa were described from soils, tree bark, and lichens. The present phylogenetic study reveals three new lineages of free‐living trebouxiophyceans found in North American desert soil crusts and proposes new generic names to accommodate them: Desertella, Eremochloris, and Xerochlorella. This survey of desert isolates also led to discovery of representatives of seven existing genera of trebouxiophyceans. Two of these genera have never been reported to contain desert representatives and one was known previously only from aquatic habitats. Furthermore, we expand the known geographic range of the recently described genus Chloropyrula, heretofore only known from the Ural Mountains. We demonstrate that the diversity of trebouxiophyceans is still underestimated and poorly understood, and that most major trebouxiophycean lineages contain desert‐dwelling taxa.     

Inhibition of dihydroceramide desaturase activity by the sphingosine kinase inhibitor SKI II

Sphingosine kinase inhibitor (SKI) II has been reported as a dual inhibitor of sphingosine kinases (SKs) 1 and 2 and has been extensively used to prove the involvement of SKs and sphingosine-1-phosphate (S1P) in cellular processes. Dihydroceramide desaturase (Des1), the last enzyme in the de novo synthesis of ceramide (Cer), regulates the balance between dihydroceramides (dhCers) and Cers. Both SKs and Des1 have interest as therapeutic targets. Here we show that SKI II is a noncompetitive inhibitor (K_i = 0.3 μM) of Des1 activity with effect also in intact cells without modifying Des1 protein levels. Molecular modeling studies support that the SKI II-induced decrease in Des1 activity could result from inhibition of NADH-cytochrome b5 reductase. SKI II, but not the SK1-specific inhibitor PF-543, provoked a remarkable accumulation of dhCers and their metabolites, while both SKI II and PF-543 reduced S1P to almost undetectable levels. SKI II, but not PF543, reduced cell proliferation with accumulation of cells in the G0/G1 phase. SKI II, but not PF543, induced autophagy. These overall findings should be taken into account when using SKI II as a pharmacological tool, as some of the effects attributed to decreased S1P may actually be caused by augmented dhCers and/or their metabolites.     

The Cleaved N-Terminus of pVI Binds Peripentonal Hexons in Mature Adenovirus

Mature human adenovirus particles contain four minor capsid proteins, in addition to the three major capsid proteins (penton base, hexon and fiber) and several proteins associated with the genomic core of the virion. Of the minor capsid proteins, VI plays several crucial roles in the infection cycle of the virus, including hexon nuclear targeting during assembly, activation of the adenovirus proteinase (AVP) during maturation and endosome escape following cell entry. VI is translated as a precursor (pVI) that is cleaved at both N- and C-termini by AVP. Whereas the role of the C-terminal fragment of pVI, pVIc, is well established as an important co-factor of AVP, the role of the N-terminal fragment, pVIn, is currently elusive. In fact, the fate of pVIn following proteolytic cleavage is completely unknown. Here, we use a combination of proteomics-based peptide identification, native mass spectrometry and hydrogen–deuterium exchange mass spectrometry to show that pVIn is associated with mature human adenovirus, where it binds at the base of peripentonal hexons in a pH-dependent manner. Our findings suggest a possible role for pVIn in targeting pVI to hexons for proper assembly of the virion and timely release of the membrane lytic mature VI molecule.     

Exploring the Biological and Chemical Complexity of the Ligases

Using a novel method to map and cluster chemical reactions, we have re-examined the chemistry of the ligases [Enzyme Commission (EC) Class 6] and their associated protein families in detail. The type of bond formed by the ligase can be automatically extracted from the equation of the reaction, replicating the EC subclass division. However, this subclass division hides considerable complexities, especially for the C–N forming ligases, which fall into at least three distinct types. The lower levels of the EC classification for ligases are somewhat arbitrary in their definition and add little to understanding their chemistry or evolution. By comparing the multi-domain architecture of the enzymes and using sequence similarity networks, we examined the links between overall reaction and evolution of the ligases. These show that, whilst many enzymes that perform the same overall chemistry group together, both convergent (similar function, different ancestral lineage) and divergent (different function, common ancestor) evolution of function are observed. However, a common theme is that a single conserved domain (often the nucleoside triphosphate binding domain) is combined with ancillary domains that provide the variation in substrate binding and function.