Agitation and Restraint in a Pediatric Psychiatric Emergency Program: Clinical Characteristics and Diagnostic Correlates.

OBJECTIVES: Agitation and restraint among pediatric psychiatric patients are a frequent, yet little studied, source of morbidity and, rarely, mortality in the emergency department (ED). This study examined agitation and restraint among youth patients in a specialized pediatric psychiatric ED, considering clinical and sociodemographic characteristics of those who required restraint to determine the clinical correlates of agitation and restraint in this population. METHODS: This descriptive study was a 6-year retrospective chart review of all patients restrained for acute agitation. Demographics, clinical characteristics, diagnoses, and reasons for restraint were collected. Relationships between sociodemographic and clinical variables to types of restraints used were examined, along with change over the study period in rate of and mean time in restraint. RESULTS: The average restraint rate was 1.94%, which remained fairly consistent throughout study period, although average time in restraint decreased significantly. Restraints were more common in males. Adolescents were overrepresented in the ED population, and after controlling for this, restraint rates were similar in adolescents and younger children. Physical aggression was the most frequent precipitant, although among adolescents verbal aggression was also a precipitant (more so than in younger children). Disruptive behavior disorder diagnoses were most frequently associated with restraint. CONCLUSIONS: A lower rate of restraint is reported here than has been seen in programs where youths are treated in medical or adult psychiatric EDs. Hospitals without specialized pediatric psychiatric emergency programs should invest in staff training in deescalation techniques and in access to pediatric psychiatric treatment. The finding that, of youth restrained, a significant proportion were under 12 years old and/or carried diagnoses not typically associated with aggressive behavior, indicates that crisis prevention, management, and treatment should include younger populations and diverse diagnostic groups, rather than focusing narrowly on older patients with psychotic or substance use disorders.

Current Advances of Nitric Oxide in Cancer and Anticancer Therapeutics.

Nitric oxide (NO) is a short-lived, ubiquitous signaling molecule that affects numerous critical functions in the body. There are markedly conflicting findings in the literature regarding the bimodal effects of NO in carcinogenesis and tumor progression, which has important consequences for treatment. Several preclinical and clinical studies have suggested that both pro- and antitumorigenic effects of NO depend on multiple aspects, including, but not limited to, tissue of generation, the level of production, the oxidative/reductive (redox) environment in which this radical is generated, the presence or absence of NO transduction elements, and the tumor microenvironment. Generally, there are four major categories of NO-based anticancer therapies: NO donors, phosphodiesterase inhibitors (PDE-i), soluble guanylyl cyclase (sGC) activators, and immunomodulators. Of these, NO donors are well studied, well characterized, and also the most promising. In this study, we review the current knowledge in this area, with an emphasis placed on the role of NO as an anticancer therapy and dysregulated molecular interactions during the evolution of cancer, highlighting the strategies that may aid in the targeting of cancer.

Tumor Microenvironment and Nitric Oxide: Concepts and Mechanisms.

The cancer tissue exists not as a single entity, but as a combination of different cellular phenotypes which, taken together, dramatically contribute to the entirety of their ecosystem, collectively termed as the tumor microenvironment (TME). The TME is composed of both immune and nonimmune cell types, stromal components, and vasculature-all of which cooperate to promote cancer progression. Not all immune cells, however, are immune-suppressive; some of them can promote the immune microenvironment to fight the invading and uncontrollably dividing cell populations at the initial stages of tumor growth. Yet, many of these processes and cellular phenotypes fall short, and the immune ecosystem more often than not ends up stabilizing in favor of the "resistant" resident cells that begin clonal expansion and may progress to metastatic forms. Stromal components, making up the extracellular matrix and basement membrane, are also not the most innocuous: CAFs embedded throughout secrete proteases that allow the onset of one of the most invasive processes-angiogenesis-through destruction of the ECM and the basement membrane. Vasculature formation, because of angiogenesis, is the largest invader of the TME and the reason metastasis happens. Vasculature is so sporadic and omnipresent in the TME that most drug therapies are mainly focused on stopping this uncontrollable process. As the tumor continues to grow, different processes are constantly supplying it with the ingredients favorable for tumor progression and eventual metastasis. For example, angiogenesis promotes blood vessel formation that will allow the bona fide escape of tumor cells to take place. Another process like hypoxia will present itself in several forms throughout the tumor (mild or acute, cycling or permanent), starting mechanisms such as epithelial to mesenchymal transitions (EMT) of resident cells and inadvertently placing the cells in such a stressful condition that production of ROS and DNA damage is unavoidable. DNA damage can induce mutagenicity while allowing resistant cells to survive. This is where drugs and treatments can subsequently suffer in effectiveness. Finally, another molecule has just surfaced as being a very important player in the TME: nitric oxide. Often overlooked and equated with ROS and initially assigned in the category of pathogenic molecules, nitric oxide can definitely do some damage by causing metabolic reprogramming and promotion of immunosuppressive phenotypes at low concentrations. However, its actions seem to be extremely dose-dependent, and this issue has become a hot target of current treatment goals. Shockingly, nitric oxide, although omnipresent in the TME, can have a positive effect on targeting the TME broadly. Thus, while the TME is a myriad of cellular phenotypes and a combination of different tumor-promoting processes, each process is interconnected into one whole: the tumor microenvironment.