Wrong-Site Procedures: Preventable Never Events that Continue to Happen

A comprehensive discussion of “never events” or preventable and grievously shocking medical errors that may result in serious morbidity and mortality is incomplete without a thorough analysis of wrong‐site procedures (WSP). These occurrences are often due to multiple, simultaneous failures in team processes and communication. Despite being relatively rare, wrong‐site surgery can be devastating to all parties involved, from patients and families to healthcare workers and hospitals. This chapter provides a general overview of the topic in the context of clinical vignettes discussing specific examples of WSP. The goal of this work is to educate the reader about risk factors and preventive strategies pertinent to WSP, with the hope of propagating the knowledge required to eliminate these “never events.” To that end, the chapter discusses pitfalls in current surgical practice that may contribute to critical safety breakdowns and emphasizes the need for multiple overlapping measures designed to improve patient safety. Furthermore, updated definitions regarding WSP are included in order to better characterize the different types of WSP. Most importantly, this chapter presents evidence‐based support for the current strategies to prevent wrong‐site events. A summary of selected recent wrong‐site occurrences is also provided as a reference for researchers in this important area of patient safety

Adverse Events during Intrahospital Transfers: Focus on Patient Safety

Intrahospital transport of patients constitutes an integral part of care delivery in the complex environment of modern hospitals. In general, the more complicated and acute the patient’s condition is, the more likely he or she will require both scheduled and unscheduled trips. The purpose of this chapter is to highlight the potential adverse events associated with intrahospital transfers (IHTs), to discuss the interdepartmental handoff process when patients travel within the walls of a single institution, and finally to provide strategies to prevent adverse events from occurring during the IHT process. A comprehensive literature review, covering some of the most recent developments in this area, has been included in this manuscript. Aspects unique to this presentation include sections dedicated to risk assessment, commonly seen patterns of transfers and complications, as well as the inclusion of family communication as a core component of the process. The overall goal of providers and patient safety champions should be the achievement of “zero incidence” rate of IHT-related events. We hope that this chapter provides a small, but significant, step in the right direction

Patient Frailty: Key Considerations, Definitions and Practical Implications

By 2020, the elderly (≥65-year-old) world population is projected to exceed one billion individuals. This demographic megatrend has brought topics such as physiological age and frailty to the forefront of medical research efforts around the globe. The concept of frailty has evolved significantly since the mid-twentieth century. The outdated stereotype of a “thin, stooped, slow octogenarian” has transitioned to a more scientific and objective understanding of the problem. Still, a comprehensive and concise definition of “frailty” remains elusive. Until such a definition is firmly established and universally agreed upon, clinicians continue to rely on the somewhat subjective conceptual framework of today. In this chapter, the authors review key issues pertaining to clinical management of frail patients, including diagnosis/identification, preventive strategies, therapeutic approaches, and common pitfalls. The relationship between frailty, various domains of life, and functional status is also discussed. Finally, we will touch upon the concepts of end-of-life and goals of care, focusing on their relationship to frailty

Subcellular specificity of cannabinoid effects in striatonigral circuits

Recent advances in neuroscience have positioned brain circuits as key units in controlling behavior, implying that their positive or negative modulation necessarily leads to specific behavioral outcomes. However, emerging evidence suggests that the activation or inhibition of specific brain circuits can actually produce multimodal behavioral outcomes. This study shows that activation of a receptor at different subcellular locations in the same neuronal circuit can determine distinct behaviors. Pharmacological activation of type 1 cannabinoid (CB1) receptors in the striatonigral circuit elicits both antinociception and catalepsy in mice. The decrease in nociception depends on the activation of plasma membrane-residing CB1 receptors (pmCB1), leading to the inhibition of cytosolic PKA activity and substance P release. By contrast, mitochondrial-associated CB1 receptors (mtCB1) located at the same terminals mediate cannabinoid-induced catalepsy through the decrease in intra-mitochondrial PKA-dependent cellular respiration and synaptic transmission. Thus, subcellular-specific CB1 receptor signaling within striatonigral circuits determines multimodal control of behavior

Experimental and Computational Mechanistic Investigation of Chlorocarbene Additions to Bridgehead Carbene–Anti-Bredt Systems: Noradamantylcarbene–Adamantene and Adamantylcarbene–Homoadamantene

Cophotolysis of noradamantyldiazirine with the phenanthride precursor of dichlorocarbene or phenylchloro­diazirine in pentane at room temperature produces noradamantylethylenes in 11% yield with slight diastereoselectivity. Cophotolysis of adamantyldiazirine with phenylchlorodiazirine in pentane at room temperature generates adamantylethylenes in 6% yield with no diastereoselectivity. ¹H NMR showed the reaction of noradamantyldiazirine + phenylchlorodiazirine to be independent of solvent, and the rate of noradamantyldiazirine consumption correlated with the rate of ethylene formation. Laser flash photolysis showed that reaction of phenylchlorocarbene + adamantene was independent of adamantene concentration. The reaction of phenylchlorocarbene + homoadamantene produces the ethylene products with <i>k</i> = 9.6 × 10⁵ M^–1 s^–1. Calculations at the UB3LYP/6-31+G­(d,p) and UM062X/6-31+G­(d,p)//UB3LYP/6-31+G­(d,p) levels show the formation of exocyclic ethylenes to proceed (a) on the singlet surface via stepwise addition of phenylchlorocarbene (PhCCl) to bridgehead alkenes adamantene and homoadamantene, respectively, producing an intermediate singlet diradical in each case, or (b) via addition of PhCCl to the diazo analogues of noradamantyl- and adamantyldiazirine. Preliminary direct dynamics calculations on adamantene + PhCCl show a high degree of recrossing (68%), indicative of a flat transition state surface. Overall, 9% of the total trajectories formed noradamantylethylene product, each proceeding via the computed singlet diradical

Extensive identification of genes involved in congenital and structural heart disorders and cardiomyopathy

Clinical presentation of congenital heart disease is heterogeneous, making identification of the disease-causing genes and their genetic pathways and mechanisms of action challenging. By using in vivo electrocardiography, transthoracic echocardiography and microcomputed tomography imaging to screen 3,894 single-gene-null mouse lines for structural and functional cardiac abnormalities, here we identify 705 lines with cardiac arrhythmia, myocardial hypertrophy and/or ventricular dilation. Among these 705 genes, 486 have not been previously associated with cardiac dysfunction in humans, and some of them represent variants of unknown relevance (VUR). Mice with mutations in Casz1, Dnajc18, Pde4dip, Rnf38 or Tmem161b genes show developmental cardiac structural abnormalities, with their human orthologs being categorized as VUR. Using UK Biobank data, we validate the importance of the DNAJC18 gene for cardiac homeostasis by showing that its loss of function is associated with altered left ventricular systolic function. Our results identify hundreds of previously unappreciated genes with potential function in congenital heart disease and suggest causal function of five VUR in congenital heart disease

Discovering dominant tumor immune archetypes in a pan-cancer census

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