A systematic review and meta-analysis of factors for delirium in vascular surgical patients

Background: Delirium is a common syndrome responsible for a large burden of morbidity and mortality. In surgical settings, research into risk factors for postoperative delirium has largely focused on elective orthopedic patients. We performed a systematic review and meta-analysis to evaluate the evidence surrounding risk factors for delirium in vascular surgical populations. Methods: Two independent reviewers searched five databases (MEDLINE, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO) from January 1987 to December 2015. We included primary research studies for incident delirium that used validated delirium assessment tools in exclusively vascular surgical populations. Results: We identified 16 studies (3817 patients) that met the inclusion criteria. There was substantial clinical heterogeneity in the populations included under a heading of “vascular surgery.” Studies were high quality, with an average Newcastle-Ottawa Scale score of 6.9. Summary incidence of delirium was 23.4% (range, 4.8%-39%). Across all studies, 157 separate risk factors were examined. Ten of the included studies used multivariable models in their analysis of risk factors. Meta-analysis of risk factors with data from more than three studies identified the following factors as conferring an increased risk of delirium: American Society of Anesthesiologists score >2 (odds ratio [OR], 3.44), renal failure (OR, 2.09), previous stroke (OR, 1.87), history of neurologic comorbidity (OR, 1.57), and male sex (OR, 1.30). Delirious patients were older (mean difference [MD], +4.99 years), had lower preoperative hemoglobin levels (MD, −0.66 g/dL), and stayed longer in intensive care units (MD, +1.06 days). Conclusions: Delirium is common in vascular surgery settings. Meta-analysis has identified significant risk factors relating to the patient, the presentation, and the pathway of care. Better understanding of these risk factors may help in prediction, prevention, and early identification of delirium

Negatively Charged Excitons and Photoluminescence in Asymmetric Quantum Well

We study photoluminescence (PL) of charged excitons ($X^-$) in narrow asymmetric quantum wells in high magnetic fields B. The binding of all $X^-$ states strongly depends on the separation $\delta$ of electron and hole layers. The most sensitive is the ``bright'' singlet, whose binding energy decreases quickly with increasing $\delta$ even at relatively small B. As a result, the value of B at which the singlet--triplet crossing occurs in the $X^-$ spectrum also depends on $\delta$ and decreases from 35 T in a symmetric 10 nm GaAs well to 16 T for $\delta=0.5$ nm. Since the critical values of $\delta$ at which different $X^-$ states unbind are surprisingly small compared to the well width, the observation of strongly bound $X^-$ states in an experimental PL spectrum implies virtually no layer displacement in the sample. This casts doubt on the interpretation of PL spectra of heterojunctions in terms of $X^-$ recombination

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele