Utilization of the Fordham Risk Screening Tool for violence risk assessment in an emergency department.

BACKGROUND: Violence is a critical problem in the emergency department (ED) and patients experiencing mental health crises are at greater violence risk; however, tools appropriate for assessing violence risk in the ED are limited. Our goal was to evaluate the utility of the Fordham Risk Screening Tool (FRST) in reliability assessing violence risk in adult ED patients with acute mental health crises through evaluation of test characteristics compared to a reference standard. METHODS: We evaluated performance of the FRST when used with a convenience sample of ED patients undergoing acute psychiatric evaluation. Participants underwent assessment with the FRST and an established reference standard, the Historical Clinical Risk Management-20, Version 3 (HCR-20 V3). Diagnostic performance was assessed through evaluation of test characteristics and area under the receiver operating characteristic curve (AUROC). Psychometric assessments examined the measurement properties of the FRST. RESULTS: A total of 105 participants were enrolled. In comparison to the reference standard, the AUROC for the predictive ability of the FRST was 0.88 (standard error 0.39, 95% confidence interval [CI] 0.81-0.96). Sensitivity was 84% (95% CI 69%-94%) while specificity was 93% (95% CI 83%-98%). The positive predictive value was 87% (95% CI 73%-94%) and negative predictive value was 91% (95% CI 83%-86%). Psychometric analyses provided reliability and validity evidence for the FRST when used in the ED setting. CONCLUSIONS: These findings support the potential utility of the FRST when used to assess violence risk in adult ED patients experiencing a mental health crisis. Future research with more diverse populations and ED settings is warranted.

Do-not-resuscitate (DNR) status and major depressive disorder (MDD): Clinical association and hospitalization outcomes.

OBJECTIVES: To understand (1) the association of Major Depressive Disorder (MDD) and do-not-resuscitate (DNR) status among hospitalized patients and (2) the association of MDD and hospitalization outcomes among DNR patients. METHODS: This was a cross-sectional analysis of United States Healthcare Cost and Utilization Project, Nationwide Inpatient Sample data from 2009 to 2013 for patients >18 years. To address the first objective, we used multivariable logistic regression among all hospitalized patients to compute the adjusted odds ratio (aOR) of having DNR status if patients have active MDD of varying severities after controlling for age, sex, race, suicidal ideation, and Elixhauser Comorbidity Index. To address the second objective, we used multivariable regression among patients with DNR status to compute aOR of having hospitalization outcomes such as increased length of stay, higher total charges, leaving against medical advice, and mortality if patients have MDD. RESULTS: Among all hospitalizations, 2.3% had DNR status. There was an inverse association between severity of MDD and having DNR status. Relative to those without MDD, patients with moderate recurrent MDD episode (aOR 0.74 (95% confidence interval (CI): 0.65-0.85) and severe recurrent MDD episode (aOR of 0.42 (95% CI: 0.37-0.48)) were significantly less likely to have DNR status. Among DNR patients, those with all severities of MDD except mild single episode MDD were >40% less likely to die during hospitalization. Among DNR patients, patients with MDD had 0.7 day longer length of stay, and >$4,500 higher total charges. SIGNIFICANCE OF RESULTS: Patients are less likely to have DNR status if they have active MDD. Among patients with DNR status, those with MDD are less likely to die during hospitalization than those without MDD. With current practice, depression is not associated with increased likelihood of death due to foregoing resuscitation prematurely, though the exact mechanisms of these findings need further investigation.

Nephrotoxic Potential of Putative 3,5-Dichloroaniline (3,5-DCA) Metabolites and Biotransformation of 3,5-DCA in Isolated Kidney Cells from Fischer 344 Rats.

The current study was designed to explore the in vitro nephrotoxic potential of four 3,5-dichloroaniline (3,5-DCA) metabolites (3,5-dichloroacetanilide, 3,5-DCAA; 3,5-dichlorophenylhydroxylamine, 3,5-DCPHA; 2-amino-4,6-dichlorophenol, 2-A-4,6-DCP; 3,5-dichloronitrobenzene, 3,5-DCNB) and to determine the renal metabolism of 3,5-DCA in vitro. In cytotoxicity testing, isolated kidney cells (IKC) from male Fischer 344 rats (~4 million/mL, 3 mL) were exposed to a metabolite (0-1.5 mM; up to 90 min) or vehicle. Of these metabolites, 3,5-DCPHA was the most potent nephrotoxicant, with 3,5-DCNB intermediate in nephrotoxic potential. 2-A-4,6-DCP and 3,5-DCAA were not cytotoxic. In separate experiments, 3,5-DCNB cytotoxicity was reduced by pretreating IKC with antioxidants and cytochrome P450, flavin monooxygenase and peroxidase inhibitors, while 3,5-DCPHA cytotoxicity was attenuated by two nucleophilic antioxidants (glutathione and N-acetyl-L-cysteine). Incubation of IKC with 3,5-DCA (0.5-1.0 mM, 90 min) produced only 3,5-DCAA and 3,5-DCNB as detectable metabolites. These data suggest that 3,5-DCNB and 3,5-DCPHA are potential nephrotoxic metabolites and may contribute to 3,5-DCA induced nephrotoxicity in vivo. In addition, the kidney can bioactivate 3,5-DCNB to toxic metabolites, and 3,5-DCPHA appears to generate reactive metabolites to contribute to 3,5-DCA nephrotoxicity. In vitro, N-oxidation of 3,5-DCA appears to be the primary mechanism of bioactivation of 3,5-DCA to nephrotoxic metabolites.

Difficult TEE Probe Placement: The Evidence, Troubleshooting Techniques, and a Guide to Alternative Monitoring Options for Intraoperative Physicians.

Transesophageal echocardiography (TEE) imaging has become an essential component of many open and interventional cardiac procedures and has increasing use in monitoring for noncardiac procedures, partly because of an aging population. Whether expected or not, encountering difficulty when inserting the TEE probe presents the anesthesiologist with a conundrum. Repeated insertion attempts increase the risk of a serious complication; however, proceeding without TEE may be unacceptable to the proceduralist or surgeon. The aim of this review is to present the spectrum of complications possible with TEE, propose several evidence-based insertion tips, examine potential alternative cardiac imaging options, and finally, propose a roadmap for providers who encounter difficulty when placing a TEE probe.

Loperamide-Associated Opioid Use Disorder and Proposal of an Alternative Treatment with Buprenorphine.

: This case report describes a patient with opioid use disorder who developed cardiac toxicity secondary to non-medical use of loperamide. At recommended doses, loperamide remains in the periphery to treat diarrhea. At high doses, loperamide causes central nervous system (CNS) opioid agonism. Complications of high-dose loperamide have been documented, including cardiotoxicity, and death. This is particularly important in light of the ongoing opioid epidemic. This case presents a patient with sequela of high-dose loperamide as an illicit opioid replacement and the subsequent loperamide toxicity, including significant QTc prolongation. Abrupt cessation of his high-dose loperamide use resulted in opioid withdrawal symptoms, which were treated with buprenorphine. Buprenorphine was selected to avoid possible worsening of QTc secondary to an additional medication, such as methadone. To our knowledge, this is the first description of the use of buprenorphine for treatment of loperamide-associated opioid use disorder. Non-medical use of loperamide requires increased recognition by the health care community, including both physicians and pharmacists, because it can result in marked and life-threatening toxicity.

Role of Free Radicals and Biotransformation in Trichloronitrobenzene-Induced Nephrotoxicity In Vitro.

This study determined the comparative nephrotoxic potential of four trichloronitrobenzenes (TCNBs) (2,3,4-; 2,4,5-; 2,4,6-; and 3,4,5-TCNB) and explored the effects of antioxidants and biotransformation inhibitors on TCNB-induced cytotoxicity in isolated renal cortical cells (IRCC) from male Fischer 344 rats. IRCC were incubated with a TCNB up to 1.0 mM for 15-120 min. Pretreatment with an antioxidant or cytochrome P450 (CYP), flavin monooxygenase (FMO), or peroxidase inhibitor was used in some experiments. Among the four TCNBs, the order of decreasing nephrotoxic potential was approximately 3,4,5- > 2,4,6- > 2,3,4- > 2,4,5-TCNB. The four TCNBs exhibited a similar profile of attenuation of cytotoxicity in response to antioxidant pretreatments. 2,3,4- and 3,4,5-TCNB cytotoxicity was attenuated by most of the biotransformation inhibitors tested, 2,4,5-TCNB cytotoxicity was only inhibited by isoniazid (CYP 2E1 inhibitor), and 2,4,6-TCNB-induced cytotoxicity was inhibited by one CYP inhibitor, one FMO inhibitor, and one peroxidase inhibitor. All of the CYP specific inhibitors tested offered some attenuation of 3,4,5-TCNB cytotoxicity. These results indicate that 3,4,5-TCNB is the most potent nephrotoxicant, free radicals play a role in the TCNB cytotoxicity, and the role of biotransformation in TCNB nephrotoxicity in vitro is variable and dependent on the position of the chloro groups.

The role of biotransformation and oxidative stress in 3,5-dichloroaniline (3,5-DCA) induced nephrotoxicity in isolated renal cortical cells from male Fischer 344 rats.

Among the mono- and dichloroanilines, 3,5-dichloroaniline (3,5-DCA) is the most potent nephrotoxicant in vivo and in vitro. However, the role of renal biotransformation in 3,5-DCA induced nephrotoxicity is unknown. The current study was designed to determine the in vitro nephrotoxic potential of 3,5-DCA in isolated renal cortical cells (IRCC) obtained from male Fischer 344 rats, and the role of renal bioactivation and oxidative stress in 3,5-DCA nephrotoxicity. IRCC (∼ 4 million cells/ml) from male rats were exposed to 3,5-DCA (0-1.0mM) for up to 120 min. In IRCC, 3,5-DCA was cytotoxic at 1.0mM by 60 min as evidenced by the increased release of lactate dehydrogenase (LDH), but 120 min was required for 3,5-DCA 0.5mM to increase LDH release. In subsequent studies, IRCC were exposed to a pretreatment (antioxidant or enzyme inhibitor) prior to exposure to 3,5-DCA (1.0mM) for 90 min. Cytotoxicity induced by 3,5-DCA was attenuated by pretreatment with inhibitors of flavin-containing monooxygenase (FMO; methimazole, N-octylamine), cytochrome P450 (CYP; piperonyl butoxide, metyrapone), or peroxidase (indomethacin, mercaptosuccinate) enzymes. Use of more selective CYP inhibitors suggested that the CYP 2C family contributed to 3,5-DCA bioactivation. Antioxidants (glutathione, N-acetyl-l-cysteine, α-tocopherol, ascorbate, pyruvate) also attenuated 3,5-DCA nephrotoxicity, but oxidized glutathione levels and the oxidized/reduced glutathione ratios were not increased. These results indicate that 3,5-DCA may be activated via several renal enzyme systems to toxic metabolites, and that free radicals, but not oxidative stress, contribute to 3,5-DCA induced nephrotoxicity in vitro.

4-Amino-2-chlorophenol: Comparative in vitro nephrotoxicity and mechanisms of bioactivation.

Chlorinated anilines are nephrotoxicants both in vivo and in vitro. The mechanism of chloroaniline nephrotoxicity may occur via more than one mechanism, but aminochlorophenol metabolites appear to contribute to the adverse in vivo effects. The purpose of this study was to compare the nephrotoxic potential of 4-aminophenol (4-AP), 4-amino-2-chlorophenol (4-A2CP), 4-amino-3-chlorophenol (4-A3CP) and 4-amino-2,6-dichlorophenol (4-A2,6DCP) using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the model and to explore renal bioactivation mechanisms for 4-A2CP. For these studies, IRCC (∼4×10(6)cells/ml) were incubated with an aminophenol (0.5 or 1.0mM) or vehicle for 60min at 37°C with shaking. In some experiments, cells were pretreated with an antioxidant or cytochrome P450 (CYP), flavin-containing monooxygenase (FMO), peroxidase or cyclooxygenase inhibitor prior to 4-A2CP (1.0mM). Lactate dehydrogenase (LDH) release served as a measure of cytotoxicity. The order of decreasing nephrotoxic potential in IRCC was 4-A2,6-DCP>4-A2CP>4-AP>4-A3CP. The cytotoxicity induced by 4-A2CP was reduced by pretreatment with the peroxidase inhibitor mercaptosuccinic acid, and some antioxidants (ascorbate, glutathione, N-acetyl-l-cysteine) but not by others (α-tocopherol, DPPD). In addition, pretreatment with the iron chelator deferoxamine, several CYP inhibitors (except for the general CYP inhibitor piperonyl butoxide), FMO inhibitors or indomethacin (a cyclooxygenase inhibitor) failed to attenuate 4-A2CP cytotoxicity. These results demonstrate that the number and ring position of chloro groups can influence the nephrotoxic potential of 4-aminochlorophenols. In addition, 4-A2CP may be bioactivated by cyclooxygenase and peroxidases, and free radicals appear to play a role in 4-A2CP cytotoxicity.

3,4,5-Trichloroaniline nephrotoxicity in vitro: potential role of free radicals and renal biotransformation.

Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60-120 min. In some experiments, IRCC were pretreated with an antioxidant or a cytochrome P450 (CYP), flavin monooxygenase (FMO), cyclooxygenase or peroxidase inhibitor prior to incubation with dimethyl sulfoxide (control) or TCA (0.5 mM) for 120 min. At 60 min, TCA did not induce cytotoxicity, but induced cytotoxicity as early as 90 min with 0.5 mM or higher TCA and at 120 min with 0.1 mM or higher TCA, as evidenced by increased lactate dehydrogenase (LDH) release. Pretreatment with the CYP inhibitor piperonyl butoxide, the cyclooxygenase inhibitor indomethacin or the peroxidase inhibitor mercaptosuccinate attenuated TCA cytotoxicity, while pretreatment with FMO inhibitors or the CYP inhibitor metyrapone had no effect on TCA nephrotoxicity. Pretreatment with an antioxidant (α-tocopherol, glutathione, ascorbate or N-acetyl-L-cysteine) also reduced or completely blocked TCA cytotoxicity. These results indicate that TCA is directly nephrotoxic to IRCC in a time and concentration dependent manner. Bioactivation of TCA to toxic metabolites by CYP, cyclooxygenase and/or peroxidase contributes to the mechanism of TCA nephrotoxicity. Lastly, free radicals play a role in TCA cytotoxicity, although the exact nature of the origin of these radicals remains to be determined.

Jail hospitalization of prearraignment patient arrestees with mental illness.

A growing number of individuals with mental illness are receiving psychiatric treatment in the criminal justice system. However, mental health problems facing individuals immediately after arrest and before arraignment have not been adequately studied. In New York City, prearraignment arrestees who require psychiatric hospitalization are temporarily transferred from police custody to correctional custody and admitted to the Bellevue Jail Psychiatry Service (BJPS) for treatment. The purpose of this study was to gain a better understanding of the impact of this jail hospitalization on the legal disposition of this vulnerable population. A retrospective chart review was conducted of 204 consecutively admitted male patient-arrestees on the BJPS. Results showed that admission to the BJPS delayed arraignment by an average of 8.03 days, with longer delays for individuals arrested outside of Manhattan. Although these delays are considered acceptable under legal precedent, concerns arise about the therapeutic impact of this practice on newly arrested individuals with severe mental illness.

Classification systems for stalking behavior.

Stalking is a complex behavioral phenomenon that is unique in that it necessarily involves a prolonged dyadic relationship between both a perpetrator and a victim. Since criminalization of stalking behavior in the 1990s, different conceptual typologies have attempted to classify this behavior to assess risk and aid in management decisions. The authors reviewed the current literature regarding the most recent and accepted stalking classification systems. The three predominant stalker typologies currently in use include Zona's stalker-victim types, Mullen's stalker typology, and the RECON stalker typology. Of these, the RECON classification system alone was developed in an attempt to separate stalkers into groups based on previously known risk factors for behaviorally based phenomenon such as propensity for violence. Understanding and simplifying these classification systems may enhance the potential that new research will lead to evidence-based management and treatment strategies in the stalking situation.

In vitro nephrotoxicity induced by propanil.

Propanil is a postemergence herbicide used primarily in rice and wheat production in the United States. The reported toxicities for propanil exposure include methemoglobinemia, immunotoxicity, and nephrotoxicity. A major metabolite of propanil, 3,4-dichloroaniline (3,4-DCA), has been shown to be a nephrotoxicant in vivo and in vitro, but the nephrotoxic potential of propanil has not been examined in detail. The purpose of this study was to determine the nephrotoxic potential of propanil using an in vitro kidney model, determine whether in vitro propanil nephrotoxicity is due to metabolites arising from propanil hydrolysis, and examine mechanistic aspects of propanil nephrotoxicity in vitro. Propanil, 3,4-DCA, propionic acid (0.1-5.0 mM), or vehicle was incubated for 15-120 min with isolated renal cortical cells (IRCC; approximately 4 million cells/mL) obtained from untreated male Fischer 344 rats. Cytotoxicity was determined by measuring lactate dehydrogenase release from IRCC. In 120-min incubations, propanil induced cytotoxicity at concentrations >0.5 mM. At 1.0 mM, propanil induced cytotoxicity following 60- or 120-min exposure. Cytotoxicity was observed with 3,4-DCA (2.0 mM) at 60 and 120 min, while propionic acid (5.0 mM) induced cytotoxicity at 60 min. In IRCC pretreated with an antioxidant, cytochrome P450(CYP) inhibitor, flavin adenine dinucleotide monooxygenase activity modulator, or cyclooxygenase inhibitor before propanil exposure (1.0 mM; 120 min), only piperonyl butoxide (0.1 mM), a CYP inhibitor, pretreatment decreased propanil cytotoxicity. These results demonstrate that propanil is an in vitro nephrotoxicant in IRCC. Propanil nephrotoxicity is not primarily due to metabolites resulting from hydrolysis of propanil, but a metabolite resulting from propanil oxidation may contribute to propanil cytotoxicity.