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Acute mania has always been one of the most intense acute psychiatric syndromes. While many controlled clinical trials of acute mania treatments have been completed in the last several decades, leading to numerous Food and Drug Administration-approved treatments, most of the questions that arise clinically remain unstudied. Many of the acute mania trials studied monotherapy or a combination of two medications for a syndrome often treated with polypharmacy. Most of the subjects in acute mania trials were only moderately ill, and even efficacious treatments had only modest effects. Mania associated with substances, a common clinical condition, was essentially excluded from most trials. Mixed episode has been studied largely as an afterthought. Traditionally, a treatment became known as a mood stabilizer if it was shown to have efficacy in mania. Evolving research in acute bipolar depression and bipolar maintenance has raised many new questions regarding the effects of mania treatments during other phases of illness. Treatment of bipolar disorder has now become highly complex, and most bipolar patients are treated with more than four medications. A lack of clear acceptance or consensus on the definitions of many crucial terms related to bipolar disorder often leads to further clinical confusion. Examples of these include mood stabilizers, hypomania (versus normal), mixed episode (versus mixed states), and antidepressant-induced mania.In this supplement, three experts present case discussions and attempt to tackle some of these commonly faced clinical problems. In each case, the experts draw from their own clinical experience to try to bridge the gap between evidence-based medicine and clinical practice. Michael H. Allen, MD, presents a case of first-episode mania without psychotic features. Many issues are discussed, including recognition of psychosis, a rationale for selecting medications from the numerous approved treatments, and subsequent implications during maintenance. In the next case, James C.-Y. Chou, MD, discusses mixed episode with psychotic features, one of the most severe among bipolar states. The topics of antipsychotics as mood stabilizers, predictors of treatment resistance, and a rationale for polypharmacy are discussed. Finally, Alan C. Swann, MD, presents three complex cases: pharmacologic mania, mania with comorbid attention-deficit/hyperactivity disorder, and antidepressant-induced destabilization during maintenance treatment. He addresses the challenging questions of when to use or avoid antidepressants in bipolar disorder, who is at risk for destabilization, and the destabilizing effects of antidepressant withdrawal. [ABSTRACT FROM AUTHOR]

It is well understood that nursing staff and physicians face potentially dangerous situations in giving care to patients. Studies have shown that patient assaults cause short- and long-term consequences for the staff, including anxiety disorders and burn-out This topic has been well discussed in the literature but focuses on inpatient settings. The authors of this article ferret out some of the differences between inpatient versus outpatient--including the differences in staffing and physical setting. Thought is given to situations that are uniquely different with the hope that clinicians might not take security for granted and possibly implement effective measures that help prevent an event from occurring. As this is not always possible, creating a protocol for likely emergent situations can be helpful 'in the moment' when thoughts are not always clear. After an incident has occurred, debriefing is critical to help prevent a related anxiety disorder and possibly reduce burn out Administrative review can be useful to help reduce further incidents. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to assess the value of a proposed classification of monochorionic placenta in reference to twin-twin transfusion syndrome.Study Design: The placentas from laser-treated patients with twin-twin transfusion syndrome and from uncomplicated monochorionic pregnancies that were delivered between January 1997 and December 2000 were included in the study. Placentas were classified as type A (no anastomoses), type B (only deep anastomoses), type C (only superficial anastomoses), and type D (deep and superficial anastomoses). The number and type of anastomoses were documented in each placental type. The severity of twin-twin transfusion syndrome was assessed in stages, as previously described. The relationship between placental types and the development and severity of twin-twin transfusion syndrome was determined.Results: One hundred thirty-one placentas were examined. Twin-twin transfusion syndrome developed in 0% (0/4 placentas) of type A, in 100% (85/85 placentas) of type B, in 5.6% (1/18 placentas) of type C, and in 79.17% (19/24 placentas) of type D placentas. An average of 4.17 (range, 1-11) vascular anastomoses was found. The mean number of superficial anastomoses was not different between patients with twin-twin transfusion syndrome and patients with no twin-twin transfusion syndrome (1.6 vs 1.71, respectively; P =.69, Student t test). The presence or absence of superficial anastomoses was not associated with differences in the severity of twin-twin transfusion syndrome.Conclusion: This classification represents a practical approach to the surgical pathologic assessment of vascular anastomoses in monochorionic placentas, with a strong clinical correlation. It also allows for the clarification of the relationship between superficial anastomoses and twin-twin transfusion syndrome. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Current treatment of patients with selective intrauterine growth retardation in monochorionic twins includes expectant management, termination of pregnancy, or umbilical-cord occlusion. The purpose of this study was to assess the outcome of monochorionic twins with selective intrauterine growth retardation who were treated with selective laser photocoagulation of the communicating vessels. STUDY DESIGN: Monochorionic twin pregnancies with selective intrauterine growth retardation at less than 26 weeks were eligible for the study. Selective intrauterine growth retardation was defined as <10th percentile for gestational age. Absent or reverse end-diastolic velocity in the umbilical artery of the twin with selective intrauterine growth retardation was required for eligibility after January 2000. RESULTS: Thirty patients met the criteria for the study: 17 patients were treated expectantly (group I); 2 patients underwent umbilical-cord ligation of the twin with selective intrauterine growth retardation, and 11 patients underwent selective laser photocoagulation of the communicating vessels (group II). Survival rates for at least 1 fetus were no different between groups I and II (14/17 [82.3%] vs 8/11 [72.3%]; P = .4). However, concomitant demise of the co-twin occurred in 4 of 7 patients, and iatrogenic premature delivery for deterioration of the twin with selective intrauterine growth retardation was necessary in 2 patients in group I, which resulted in significant neonatal morbidity. Of the live-born babies, neurologic handicap was present in 3 of 22 babies (13.6%) versus 0 of 12 in groups I and II, respectively (P < .0001). CONCLUSION: Selective intrauterine growth retardation in monochorionic twins can be effectively treated with selective laser photocoagulation of the communicating vessels. By unlinking the circulations between the fetuses, the pregnancy is rendered 'functionally' dichorionic, which improves pregnancy treatment and results in decreased neonatal morbidity. This approach constitutes a new valuable alternative in the treatment of monochorionic twin pregnancies with selective intrauterine growth retardation. A randomized clinical trial of expectant treatment versus selective laser photocoagulation of the communicating vessels for monochorionic selective intrauterine growth retardation can be considered. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Vesicoamniotic shunting may be difficult or impossible in selected cases of fetal lower obstructive uropathy. The purpose of this article is to describe the performance of fetal hydrolaparoscopy and endoscopic fetal cystotomy in two fetuses with complicated lower obstructive uropathy. STUDY DESIGN: Fetal hydrolaparoscopy-endoscopic fetal cystotomy was performed in a patient with a markedly thickened bladder that could not be entered percutaneously. A peritoneoamniotic (bridge) shunt was also placed. Fetal hydrolaparoscopy-endoscopic fetal cystotomy was performed in a second patient with a collapsed bladder from a previous vesicocentesis, because vesicoinfusion resulted in further ascites. Fetal cystoscopy was performed after endoscopic fetal cystotomy, and posterior urethral valves were ablated with neodymium:yttrium-aluminum-garnet laser energy. A vesicoamniotic shunt was left in place. RESULTS: Adequate bladder drainage was obtained in both cases. The first baby required bilateral nephrotomy and a permanent cystotomy at birth and is scheduled for a bladder expansion procedure at the age of year. The second patient had premature rupture of membranes and fetal death from treatment of this complication 5 days after the original procedure. CONCLUSION: Fetal hydrolaparoscopy-endoscopic fetal cystotomy can be performed in complicated cases of lower obstructive uropathy. The procedure involves the creation of a defect in the bladder dome under direct endoscopic visualization within a spontaneous or intentional hydroperitoneum. Peritoneoamniotic shunting, vesicoamniotic shunting, or ablation of posterior urethral valves may then be performed. Fetal hydrolaparoscopy-endoscopic fetal cystotomy should be reserved only for complicated cases of lower obstructive uropathy in which conventional vesicoamniotic shunting is not safely possible. Further experience with fetal hydrolaparoscopy-endoscopic fetal cystotomy is necessary to establish its risks and benefits. [ABSTRACT FROM AUTHOR]

Selective laser photocoagulation of communicating vessels (SLPCV) is an application of minimally invasive endoscopic fetal surgery (ie, surgical fetoscopy) performed for severe cases of twin-to-twin transfusion syndrome (MS), a complication of monochorionic twin pregnancies. Advances in ultrasound and endoscopy have aided the identification and treatment of this potentially lethal or fatal condition. Surgical fetoscopy, an innovation in the field of surgery and maternal-fetal medicine, benefits patients by reducing the morbidity and mortality associated with MS, with minimal risks to the mother. [ABSTRACT FROM AUTHOR]

Objective: The effectiveness of suicide risk screening relative to depression screening alone among primary care patients has not been tested rigorously. This study compared the performance of multiple depression screening methods (Patient Health Questionnaire [PHQ]-2, PHQ-8, and PHQ-9) and multiple suicide risk screening methods (PHQ-9 item 9 and suicide-focused screening of "thoughts of killing yourself" during the entire lifespan, within the past month, and within the past week) in a convenience sample of primary care patients., Methods: A total of 2,744 patients (military personnel, family members, and retirees) from six military primary care clinics completed the PHQ-9 and screening for suicidal ideation (SI) during routine clinic visits. Follow-up phone interviews were conducted for one year post-baseline to assess the incidence of suicide attempts, the study's primary outcome. Sensitivity, specificity, accuracy, and F1 statistics were calculated for each screening method for identifying patients who attempted suicide., Results: More than 65% of patients who screened positive for SI also screened positive for depression on the PHQ-9. Depression screening with the PHQ-9 correctly identified more patients who attempted suicide during follow-up than the PHQ-2, past week SI, and past month SI. The PHQ-9 correctly identified more patients who attempted suicide within 3 months than lifetime SI, but lifetime SI correctly identified more patients who attempted suicide within 6 and 12 months., Conclusion: Depression screening with the PHQ-9 was the most effective strategy for identifying patients who attempted suicide in the near term. Universal suicide risk screening is unlikely to meaningfully improve identification of higher-risk patients beyond PHQ-9 depression screening., (Copyright © 2023 The Joint Commission. All rights reserved.)

Background: Approximately half of those who attempt suicide report experiencing suicidal ideation and suicidal planning in advance; others deny these experiences. Some researchers have hypothesized that rapid intensification is due to past suicidal ideation and/or behaviors that are "mentally shelved" but remain available for rapid access later., Method: To evaluate this hypothesis, we examined (a) temporal sequencing of suicidal ideation, suicidal planning, and suicidal behavior, and (b) speed of emergence of suicidal behavior in a prospective cohort study of 2744 primary care patients., Results: Of 52 patients reporting suicidal behavior during follow-up, 20 (38.5%) reported suicidal ideation and planning prior to their suicidal behavior, 23 (44.2%) reported suicidal ideation but not planning, and nine (17.3%) denied both suicidal ideation and planning. Over half (n = 30, 57.7%) reported the onset of suicidal ideation and/or planning on the same day as or after their suicidal behavior (i.e., rapid intensification). Rapid intensification was not associated with increased likelihood of reporting recent or past suicidal ideation, planning, or behaviors, suggesting rapid intensification does not depend on prior experience with suicidal ideation and/or behaviors., Conclusion: Detecting primary care patients at risk for this form of suicidal behavior may be limited even with universal suicide risk screening., (© 2023 The Authors. Suicide and Life-Threatening Behavior published by Wiley Periodicals LLC on behalf of American Association of Suicidology.)

Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6-36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.

Background: Approximately half of patients who attempt or die by suicide screened negative for suicidal ideation during their most recent medical visit. Maladaptive beliefs and schemas can increase cognitive vulnerability to suicidal behavior, even among patients without recent or past suicidal thoughts and behaviors. Assessing these beliefs could improve the detection of patients who will engage in suicidal behavior after screening negative for elevated suicide risk., Methods: Primary care patients who completed the Patient Health Questionnaire-9 and the Suicide Cognitions Scale-Revised (SCS-R) during routine clinic visits and denied suicidal ideation at baseline (N = 2417) were included in the study sample. Suicidal behaviors during the 12 months after baseline were assessed. Logistic regression analyses examined the association of baseline SCS-R scores with later suicidal behavior., Results: In both univariate and multivariate analyses, SCS-R total scores were associated with significantly increased risk of suicidal behavior within 90, 180, and 365 days post-baseline. Results were unchanged when patients who reported prior suicidal behavior were excluded (N = 2178). In item-level analyses, all 16 SCS-R items significantly differentiated patients with and without follow-up suicidal behavior., Limitations: Study limitations included missing follow-up data, restriction of sample to U.S. military medical beneficiaries, and inability to assess representativeness of the sample relative to the full primary care population., Conclusions: SCS-R scores are elevated among patients who attempt suicide after denying both suicidal ideation and prior suicide attempts, suggesting the scale may reflect enduring suicide risk. The SCS-R could enhance suicide risk screening and assessment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Suicide rates are extremely high among emergency department patients seen for deliberate self-harm. Inpatient hospitalization is often recommended for these patients, but evidence on the suicide prevention impacts of hospitalization is scarce. Confounding by indication and challenges to implementing randomized designs are barriers to advances in this field., Methods: Investigators used 2009-2012 statewide data on 57,312 self-harm emergency department patients from California, linked to mortality records. Naive 12-month and 30-day suicide risks were estimated among patients who were hospitalized versus those who were discharged. Then, generalized random forest methods were applied to estimate the average treatment impacts of hospitalization on suicide, conditioning on observable covariates. Associations were calculated separately for sex- and age-specific subgroups. Analyses were conducted in February 2019-August 2021., Results: In naive analyses, suicide risk was significantly higher in hospitalized than in discharged patients in each subgroup. In 12-month models accounting for the observed covariates through generalized random forest methods, hospitalized male patients had 5.4 more suicides per 1,000 patients (95% CI=3.0, 7.8), hospitalized patients aged 10-29 years had 2.4 more suicides per 1,000 (95% CI=1.1, 3.6), and those aged ≥50 years had 5.8 more suicides per 1,000 (95% CI=0.5, 11.2) than corresponding discharged patients. Hospitalization was not significantly associated with suicide among female patients or patients aged 30-49 years in generalized random forest analyses. Patterns were similar in 30-day generalized random forest models., Conclusions: Emergency department personnel intend to hospitalize self-harm patients with high suicide risk; this study suggests that this goal is largely realized. Analyses that control for confounding by observable covariates did not find clear evidence that hospitalization reduces suicide risk and could not rule out the possibility of iatrogenic effects., (Copyright © 2021 American Journal of Preventive Medicine. All rights reserved.)

Purpose: Over 95% of patients who screen positive on the Patient Health Questionnaire-9 (PHQ-9) suicide risk item do not attempt or die by suicide, which could lead to unnecessary treatment and/or misallocation of limited resources. The present study seeks to determine if suicide risk screening can be meaningfully improved to identify the highest-risk patients., Methods: Patients eligible to receive medical treatment from the US Department of Defense medical system were recruited from 6 military primary care clinics located at 5 military installations around the United States. Patients completed self-report measures including the PHQ-9 and 16 items from the Suicide Cognitions Scale (SCS) during routine primary care clinic visits. Postbaseline suicidal behaviors (suicide attempts, interrupted attempts, and aborted attempts) were assessed by evaluators who were blind to screening results using the Self-Injurious Thoughts and Behaviors Interview., Results: Among 2,744 patients, 13 (0.5%) engaged in suicidal behavior in the 30 days after screening and 28 (1.0%) displayed suicidal behavior in the 90 days after screening. Multiple SCS items differentiated patients with suicidal behavior less than 30 days after screening positive for suicide risk. Augmenting the PHQ-9 suicide risk item with SCS items improved the identification of patients who were most likely to have suicidal behavior within a month of screening positive without sacrificing sensitivity., Conclusion: Among primary care patients who screen positive for suicide risk on the PHQ-9, SCS items improved screening efficiency by identifying those patients who are most likely to engage in suicidal behavior within the next 30 days., (© 2021 Annals of Family Medicine, Inc.)

The measurement of self-reported suicide risk can be complicated in medical settings due to patient apprehension about the potential consequences of self-disclosure. The Suicide Cognitions Scale (SCS) was designed to assess suicide risk by measuring a range of suicidogenic cognitions (e.g., hopelessness, perceived burdensomeness) collectively referred to as the suicidal belief system. The SCS's concurrent, known groups, and prospective validity for suicidal thoughts and behaviors have previously been supported. The present study examined the factor structure, known-groups, and concurrent validity of a revised, 16-item version of the SCS (SCS-R), which removed two items that explicitly used the word "suicide" and changed item scoring from a 1-5 to 0-4 scale, thereby improving the interpretation of scores. In a sample of 2,690 primary care patients presenting for routine medical care at one of six US military clinics, results of bifactor analysis supported the scale's unidimensionality. The SCS-R significantly differentiated participants with a history of suicide attempts and was significantly correlated with frequency of thoughts about death and self-harm during the previous 2 weeks. Results align with earlier research and provide psychometric support for the SCS-R., Competing Interests: No potential conflict of interest was reported by the authors., (© 2021 Society for Military Psychology, Division 19 of the American Psychological Association.)

Background: There are few rapidly acting treatments for acute suicidality or treatment-resistant depression. Propofol (2,6-diisopropylphenol) is an intravenous anesthetic agent used in outpatient settings. It is a gamma-aminobutyric acid type A agonist and has affinity at the N-methyl-D-aspartate receptor. Elevation in mood and sociality in humans has been observed following propofol-induced anesthesia. Other authors reported an open-label study of repeated dosing of propofol in treatment-resistant depression in which several patients experienced sustained improvement. Recently, we reported that in a rodent model of despair, a forced swim test, 45 minutes after administration of 50 mg/kg propofol, immobility time was significantly reduced., Objective: The objective of the experiment was to determine whether the antidepressant-like effects of a single dose of propofol in mice are sustained for 24 hours., Methods: The time spent immobile during a forced swim test 24 hours after intraperitoneal administration of a single dose of propofol 50 mg/kg or 0.9% saline was evaluated in 24 adult male mice (C57/BL6). Immobility time was quantified and evaluated with a custom video analysis software program., Results: Propofol-treated mice were immobile for a mean (SEM) time of 115 (13) seconds, whereas saline-treated mice were immobile for a mean (SEM) time of 94 (14) seconds. A 2-tailed unpaired t test found no significant difference between the treatment groups ( t  = 1.07, df = 22; P  = 0.30)., Conclusions: Twenty-four hours after intraperitoneal administration, the effect of propofol on immobility time was not statistically significantly different from vehicle. However, given our previous report of at least a short-term benefit of propofol on struggling time in the forced swim time and an encouraging pilot study in humans with treatment-resistant depression, further evaluation of propofol's antidepressant potential may be warranted., (© 2020 The Author(s).)

Objective: Suicide screening followed by an intervention may identify suicidal individuals and prevent recurring self-harm, but few cost-effectiveness studies have been conducted. This study sought to determine whether the increased costs of implementing screening and intervention in hospital emergency departments (EDs) are justified by improvements in patient outcomes (decreased attempts and deaths by suicide)., Methods: The Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE) study recruited participants in eight U.S. EDs between August 2010 and November 2013. The eight sites sequentially implemented two interventions: universal screening added to treatment as usual and universal screening plus a telephone-based intervention delivered over 12 months post-ED visit. This study calculated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves to evaluate screening and suicide outcome measures and costs for the two interventions relative to treatment as usual. Costs were calculated from the provider perspective (e.g., wage and salary data and rental costs for hospital space) per patient and per site., Results: Average per-patient costs to a participating ED of universal screening plus intervention were $1,063 per month, approximately $500 more than universal screening added to treatment as usual. Universal screening plus intervention was more effective in preventing suicides compared with universal screening added to treatment as usual and treatment as usual alone., Conclusions: Although the choice of universal screening plus intervention depends on the value placed on the outcome by decision makers, results suggest that implementing such suicide prevention measures can lead to significant cost savings.

Background: Many emergency department (ED) patients are at risk of suicide, and the ED is a key setting for suicide prevention. Although ED interventions are associated with reduced suicide attempts and societal costs, most EDs do not have follow-up programs. This pilot investigated the feasibility and implementation process of a statewide program., Methods: This multicenter prospective pilot program included all patients evaluated for suicidal behavior in, and discharged home from, participating EDs across Colorado. Suicidal ED patients were offered crisis hotline follow-up calls that focused on continued support and connection to outpatient care. Data collection at EDs focused on implementation issues and referral and participation rates; the crisis line collected patient information and call statistics., Results: From July 1, 2015, to October 31, 2017, the program expanded to 15 EDs covering almost a quarter of ED visits in a large, high-burden state. Some sites achieved 100% referral rates, suggesting that referral became routine, and the mean referral rate was 76%. High referral rates were associated with an ED champion, record system enhancements, repeated training, and regular communication. Of 5,620 visits with referral, 2,737 resulted in participation (48.7%). Although the program was free for patients, half declined it. The call center made 15,414 calls, ultimately reaching all but 9.8% of participants. Few participants reported repeat ED visits or suicide attempts., Conclusion: This project demonstrated the feasibility of using a state crisis hotline to provide postdischarge follow-up for suicidal ED patients. Continued investigation into sustainable implementation and outcomes of such programs is warranted., (Copyright © 2019. Published by Elsevier Inc.)

In clinical practice, welfare checks have become a fairly common aspect of suicide prevention. At the same time, the medical literature provides almost no guidance to inform clinicians under what circumstances welfare checks should be requested, how best to go about placing those requests, or how to document decision-making related to this important subject. Literature searches spanning both PubMed and Google Scholar failed to yield any applicable results. Performed correctly, welfare checks have the potential to be life-saving interventions for persons in suicidal crises. Performed incorrectly, welfare checks may become an overly defensive practice that damages therapeutic relationships, violates patients' rights, and consumes important and limited community resources. The need for thoughtful guidance to assist clinicians in navigating these difficult clinical scenarios is long overdue. This column, the second in a 2-part series, offers an approach to welfare checks informed by the tenets of therapeutic risk management.

In clinical practice, welfare checks have become a fairly common aspect of suicide prevention. At the same time, there is almost no guidance in the medical literature to inform clinicians under what circumstances welfare checks should be requested, how best to go about placing those requests, or how to document decision-making around this important subject. Literature searches spanning both PubMed and Google Scholar fail to yield any applicable results. Performed correctly, welfare checks have the potential to be life-saving interventions for persons in suicidal crises. Performed incorrectly, the welfare check may become an overly defensive practice that damages therapeutic relationships, violates patients' rights, and consumes important and limited community resources. The need for thoughtful guidance to assist clinicians in navigating these difficult clinical scenarios is long overdue. This article, the first in a 2-part series, will describe welfare checks and explore their potential risks and benefits.

Objective: Propofol (2,6-diisopropylphenol) is a gamma-aminobutyric acid type A agonist intravenous anesthetic agent used in outpatient settings. Based on anecdotal reports of improved mood in humans following propofol-induced anesthesia, the impact of acute propofol treatment alone or in combination with subchronic fluoxetine dosing was tested on forced swim test (FST) performance. Design: Seventy-two adult male mice (C57/BL6, CRL-provided) were pretreated daily with saline or fluoxetine (20 mg/kg, intraperitoneally) (21 days for cohort 1; 24 days for cohort 2). At 24 hours after the last pretreatment injection, the mice received saline or propofol (35 or 50 mg/kg, intraperitoneally). Then, 45 minutes later, the mice underwent a five-minute FST. Immobility time was quantified and evaluated with a custom video-analysis software program. Results: A one-way analysis of variance indicated statistically significant effects of propofol on immobility time in cohorts 1 and 2. A comparison performed using Dunnett's method revealed that propofol 50 mg/kg (p < 0.05) but not 35 mg/kg (p = not significant) reduced immobility time as compared with in the saline-saline control group (difference between means of 38.42 and 16.46 seconds, respectively). Conclusion: In comparison with saline, propofol significantly decreased immobility time during the FST, which models depression and resilience to stress. Our preclinical results are consistent with a small open-label study of propofol used in treatment-resistant depression recently reported by Mickey BJ, White AT, Arp AM, et al (2018). Further investigation of propofol regarding its potential antidepressant effects seems warranted., Competing Interests: FUNDING:Support for this study was provided by Bioniche Global Development, LLC. DISCLOSURES:Dr. Daniel is the president of Bioniche Global Development, LLC, which has an intellectual property interest in propofol for the rapid treatment of depression and suicidality. Dr. Allen, Ms. Copeland Flynn, Noah Daniel and Donald Daniel are consultants to Bioniche Development., (Copyright © 2019. Matrix Medical Communications. All rights reserved.)

Background: Primary care is the most frequently visited clinic type immediately prior to suicidal behavior, with nearly half of suicide decedents visiting a primary care provider within a month of their death. Data supporting the efficacy of suicide risk screening in this setting is lacking, however. Improved suicide risk screening in primary care could lead to earlier intervention and treatment., Purpose: The PRImary care Screening Methods (PRISM) study is designed to develop and evaluate the efficacy of an alert algorithm that can be used by military primary care providers to accurately identify high-risk patients, to improve the identification of high-risk patients who deny suicidal thoughts, and to quantify patient subgroups who are more likely to be missed by existing screening methods (i.e., false negatives)., Methods: The rationale of the PRISM study is discussed, along with ethical and design considerations related to the conduct of suicide prevention research. The PRISM study enrolled 2690 patients from six primary care clinics across the U.S. Patients were enrolled during routine visits to a primary care clinic, and completed a battery of self-report scales in clinic waiting rooms. Follow-up phone interviews are conducted 1, 6, and 12 months after enrollment. The primary outcome is suicide attempt., Conclusions: PRISM is the first study to prospectively examine multiple suicide risk screening methods in "real-world" military primary care clinics. Ethical and design issues were considered to ensure that human participants, especially suicidal patients, were adequately protected while minimizing the potential confounding effect of risk management protocols., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Acne vulgaris is a highly heritable common, chronic inflammatory disease of the skin for which five genetic risk loci have so far been identified. Here, we perform a genome-wide association study of 3823 cases and 16,144 controls followed by meta-analysis with summary statistics from a previous study, with a total sample size of 26,722. We identify 20 independent association signals at 15 risk loci, 12 of which have not been previously implicated in the disease. Likely causal variants disrupt the coding region of WNT10A and a P63 transcription factor binding site in SEMA4B. Risk alleles at the 1q25 locus are associated with increased expression of LAMC2, in which biallelic loss-of-function mutations cause the blistering skin disease epidermolysis bullosa. These findings indicate that variation affecting the structure and maintenance of the skin, in particular the pilosebaceous unit, is a critical aspect of the genetic predisposition to severe acne.

Emergency department (ED) clinicians routinely decide the disposition of patients with suicidal ideation, with potential consequences for patient safety, liability, and system costs and resources. An expert consensus panel recently created a 6-item decision support tool for patients with passive or active suicidal ideation. Individuals scoring a 0 (exhibiting none of the tool's 6 items) are considered "lower risk" and suitable for discharge, while those with non-0 scores are considered "elevated risk" and should receive further evaluation. The current study tested the predictive utility of this tool using existing data from the Emergency Department Safety Assessment and Follow-up Evaluation. ED patients with active suicide ideation (n = 1368) were followed for 12 months after an index visit using telephone assessment and medical chart review. About 1 in 5 patients had attempted suicide during follow-up. Because of the frequency of serious warning signs and risk factors in this population, only three patients met tool criteria for "lower risk" at baseline. The tool had perfect sensitivity, but exceptionally low specificity, in predicting suicidal behavior within 6 weeks and 12 months. In logistic regression analyses, several tool items were significantly associated with suicidal behavior within 6 weeks (suicide plan, past attempt) and 12 months (suicide plan, past attempt, suicide intent, significant mental health condition, irritability/agitation/aggression). Although the tool did not perform well as a binary instrument among those with active suicidal ideation, having a suicide plan identified almost all attempters while suicide plan and past attempt identified over four-fifths of near-term attempts. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Reno, Elaine, Talia L. Brown, Marian E. Betz, Michael H. Allen, Lilian Hoffecker, Jeremy Reitinger, Robert Roach, and Benjamin Honigman. Suicide and high altitude: an integrative review. High Alt Med Biol 19:99-108, 2018., Introduction: Suicide rates are greater at high altitudes, and multiple mechanisms have been suggested for this relationship, including hypoxia, differences in population density, characteristics of suicide victims, and firearms ownership and access. To better understand these potential mechanisms, studies evaluating the associations between high altitude and suicide were examined., Methods: A literature review of published studies on high altitude and suicide was conducted in Medline, Embase, Web of Science, the Cochrane Database of Systematic Reviews, and the Cochrane CENTRAL database. We extracted and analyzed all studies that met the inclusion criteria, excluding foreign language studies and letters. Most of the measurements and results were synthesized using modified Letts' criteria., Results: Searches using an extensive list of keywords returned 470 articles, but only 6 met the inclusion criteria. The studies' samples ranged in size from 8871 to 596,704, while studies which did not document sample size reported suicide rates. In five of the studies selected, individuals living at high altitudes were at greater risk of suicide. Four studies used aggregated data at a county or state level to analyze variables, such as age, gender, race, socioeconomic factors, and firearms access. All the studies found that high altitude was independently associated with suicide. One study found that many individual characteristics of those who committed suicide were different at high altitudes than low altitude, including a lack of access or barriers to mental healthcare. Depression exacerbated by hypoxia was hypothesized as a possible biologic mechanism in three studies., Conclusion: These research studies published since 2009 support an association between high altitude and suicide rates at the state or county level, but do not provide sufficient data to estimate the effect of high altitude on an individuals' suicide risk. Although the impact of hypoxia on mood and depression has been hypothesized to be a contributing cause, many other individual factors likely play more important roles.

Objective: This study estimated the expected cost-effectiveness and population impact of outpatient interventions to reduce suicide risk among patients presenting to general hospital emergency departments (EDs), compared with usual care. Several such interventions have been found efficacious, but none is yet widespread, and the cost-effectiveness of population-based implementation is unknown., Methods: Modeled cost-effectiveness analysis compared three ED-initiated suicide prevention interventions previously found to be efficacious-follow-up via postcards or caring letters, follow-up via telephone outreach, and suicide-focused cognitive-behavioral therapy (CBT)-with usual care. Primary outcomes were treatment costs, suicides, and life-years saved, evaluated over the year after the index ED visit., Results: Compared with usual care, adding postcards improved outcomes and reduced costs. Adding telephone outreach and suicide-focused CBT, respectively, improved outcomes at a mean incremental cost of $4,300 and $18,800 per life-year saved, respectively. Monte Carlo simulation (1,000 repetitions) revealed the chance of incremental cost-effectiveness to be a certainty for all three interventions, assuming societal willingness to pay ≥$50,000 per life-year. These main findings were robust to various sensitivity analyses, including conservative assumptions about effect size and incremental costs. Population impact was limited by low sensitivity of detecting ED patients' suicide risk, and health care delivery inefficiencies., Conclusions: The highly favorable cost-effectiveness found for each outpatient intervention provides a strong basis for widespread implementation of any or all of the interventions. The estimated population benefits of doing so would be enhanced by increasing the sensitivity of suicide risk detection among individuals presenting to general hospital EDs.

Rationale: The rapid screening of volatile organic compounds (VOCs) by direct analysis has potential applications in the areas of food and flavour science. Currently, the technique of choice for VOC analysis is gas chromatography/mass spectrometry (GC/MS). However, the long chromatographic run times and elaborate sample preparation associated with this technique have led a movement towards direct analysis techniques, such as selected ion flow tube mass spectrometry (SIFT-MS), proton transfer reaction mass spectrometry (PTR-MS) and electronic noses. The work presented here describes the design and construction of a Venturi jet-pump-based modification for a compact mass spectrometer which enables the direct introduction of volatiles for qualitative and quantitative analysis., Methods: Volatile organic compounds were extracted from the headspace of heated vials into the atmospheric pressure chemical ionization source of a quadrupole mass spectrometer using a Venturi pump. Samples were analysed directly with no prior sample preparation. Principal component analysis (PCA) was used to differentiate between different classes of samples., Results: The interface is shown to be able to routinely detect problem analytes such as fatty acids and biogenic amines without the requirement of a derivatisation step, and is shown to be able to discriminate between four different varieties of cheese with good intra and inter-day reproducibility using an unsupervised PCA model. Quantitative analysis is demonstrated using indole standards with limits of detection and quantification of 0.395 μg/mL and 1.316 μg/mL, respectively., Conclusions: The described methodology can routinely detect highly reactive analytes such as volatile fatty acids and diamines without the need for a derivatisation step or lengthy chromatographic separations. The capability of the system was demonstrated by discriminating between different varieties of cheese and monitoring the spoilage of meats., (© 2017 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd.)

Objective: This post hoc analysis evaluated the effect of lurasidone on agitation in acutely ill patients with schizophrenia., Method: Patient-level data were pooled from five 6-week, randomized, double-blind, placebo-controlled studies of fixed-dose, once-daily, oral lurasidone (40, 80, 120, or 160 mg/d). Agitation was assessed with the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) score, utilizing a mixed model for repeated measurement analysis., Results: In patients with higher levels of agitation at baseline (PANSS-EC score≥14; n=773), lurasidone was associated with significantly greater improvement in least-squares (LS) mean PANSS-EC scores versus placebo at Day 3/4 (-1.6 vs -1.0; p<0.05), Day 7 (-2.3 vs -1.6; p<0.05), and at Week 6 endpoint (-5.5 vs -3.8; p<0.001; effect size=0.43). In patients with lower agitation at baseline (PANSS-EC score<14; n=754), LS mean PANSS-EC score change was significantly greater for lurasidone compared with placebo at Day 7 (-0.8 vs -0.1; p<0. 01) through Week 6 endpoint (-1.9 vs -0.9; p<0.001; effect size=0.31). Higher doses of lurasidone were notably more effective than lower doses in patients with more severe agitation at study baseline., Conclusion: In this pooled analysis of 5 short-term studies, lurasidone provided early and sustained reduction in agitation, assessed using the PANSS-EC score, in patients with an acute exacerbation of schizophrenia. Higher doses of lurasidone were particularly effective in patients with more severe agitation at study baseline. Overall, these results suggest that lurasidone may be a useful treatment option for patients exhibiting agitation associated with acute psychotic symptoms of schizophrenia. ClinicalTrials.gov Identifiers: NCT00088634 (Study D1050196); NCT00549718 (Study D1050229), NCT00615433 (Study D1050231); NCT00790192 (Study D1050233). Study D1050006 was completed prior to the requirement to register trials., (Copyright © 2017 Sunovion Pharmaceuticals Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: The emergency medical evaluation of psychiatric patients presenting to United States emergency departments (ED), usually termed "medical clearance," often varies between EDs. A task force of the American Association for Emergency Psychiatry (AAEP), consisting of physicians from emergency medicine, physicians from psychiatry and a psychologist, was convened to form consensus recommendations for the medical evaluation of psychiatric patients presenting to U.S.EDs., Methods: The task force reviewed existing literature on the topic of medical evaluation of psychiatric patients in the ED and then combined this with expert consensus. Consensus was achieved by group discussion as well as iterative revisions of the written document. The document was reviewed and approved by the AAEP Board of Directors., Results: Eight recommendations were formulated. These recommendations cover various topics in emergency medical examination of psychiatric patients, including goals of medical screening in the ED, the identification of patients at low risk for co-existing medical disease, key elements in the ED evaluation of psychiatric patients including those with cognitive disorders, specific language replacing the term "medical clearance," and the need for better science in this area., Conclusion: The evidence indicates that a thorough history and physical examination, including vital signs and mental status examination, are the minimum necessary elements in the evaluation of psychiatric patients. With respect to laboratory testing, the picture is less clear and much more controversial., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

Importance: Suicide is a leading cause of deaths in the United States. Although the emergency department (ED) is an opportune setting for initiating suicide prevention efforts, ED-initiated suicide prevention interventions remain underdeveloped., Objective: To determine whether an ED-initiated intervention reduces subsequent suicidal behavior., Design, Setting, and Participants: This multicenter study of 8 EDs in the United States enrolled adults with a recent suicide attempt or ideation and was composed of 3 sequential phases: (1) a treatment as usual (TAU) phase from August 2010 to December 2011, (2) a universal screening (screening) phase from September 2011 to December 2012, and (3) a universal screening plus intervention (intervention) phase from July 2012 to November 2013., Interventions: Screening consisted of universal suicide risk screening. The intervention phase consisted of universal screening plus an intervention, which included secondary suicide risk screening by the ED physician, discharge resources, and post-ED telephone calls focused on reducing suicide risk., Main Outcomes and Measures: The primary outcome was suicide attempts (nonfatal and fatal) over the 52-week follow-up period. The proportion and total number of attempts were analyzed., Results: A total of 1376 participants were recruited, including 769 females (55.9%) with a median (interquartile range) age of 37 (26-47) years. A total of 288 participants (20.9%) made at least 1 suicide attempt, and there were 548 total suicide attempts among participants. There were no significant differences in risk reduction between the TAU and screening phases (23% vs 22%, respectively). However, compared with the TAU phase, patients in the intervention phase showed a 5% absolute reduction in suicide attempt risk (23% vs 18%), with a relative risk reduction of 20%. Participants in the intervention phase had 30% fewer total suicide attempts than participants in the TAU phase. Negative binomial regression analysis indicated that the participants in the intervention phase had significantly fewer total suicide attempts than participants in the TAU phase (incidence rate ratio, 0.72; 95% CI, 0.52-1.00; P = .05) but no differences between the TAU and screening phases (incidence rate ratio, 1.00; 95% CI, 0.71-1.41; P = .99)., Conclusions and Relevance: Among at-risk patients in the ED, a combination of brief interventions administered both during and after the ED visit decreased post-ED suicidal behavior.

Introduction: In the United States, the number of patients presenting to the emergency department (ED) for a mental health concern is significant and expected to grow. The breadth of the medical evaluation of these patients is controversial. Attempts have been made to establish a standard evaluation for these patients, but to date no nationally accepted standards exist. A task force of the American Association of Emergency Psychiatry, consisting of physicians from emergency medicine and psychiatry, and a psychologist was convened to form consensus recommendations on the medical evaluation of psychiatric patients presenting to EDs., Methods: The task force reviewed existing literature on the topic of medical evaluation of psychiatric patients in the ED (Part I) and then combined this with expert consensus (Part II)., Results: In Part I, we discuss terminological issues and existing evidence on medical exams and laboratory studies of psychiatric patients in the ED., Conclusion: Emergency physicians should work cooperatively with psychiatric receiving facilities to decrease unnecessary testing while increasing the quality of medical screening exams for psychiatric patients who present to EDs., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. The authors disclosed none.

This study evaluated the concurrent validity of a brief suicide risk screener for adults in the emergency department (ED). Two versions of the verbally administered Patient Safety Screener (2-item, 3-item) were compared to a reference standard, the Beck Scale for Suicide Ideation (BSSI). Analyses included measures of agreement (Kappa). Agreement between the Patient Safety Screener-2 and -3 and the BSSI (n = 951) was almost perfect for overall positive screening (K = 0.94-0.95) and past suicide attempts (K = 0.97-0.98). Agreement on ideation ranged from fair (K = 0.34) for the 2 item version to good (K = 0.61) for the 3 item version. The Patient Safety Screener's concurrent validity with the BSSI ranged from fair to almost perfect and warrants additional study.

Background: Health services often manage agitated or violent people, and such behaviour is particularly prevalent in emergency psychiatric services (10%). The drugs used in such situations should ensure that the person becomes calm swiftly and safely., Objectives: To examine whether haloperidol plus promethazine is an effective treatment for psychosis-induced aggression., Search Methods: On 6 May 2015 we searched the Cochrane Schizophrenia Group's Register of Trials, which is compiled by systematic searches of major resources (including MEDLINE, EMBASE, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings., Selection Criteria: All randomised clinical trials with useable data focusing on haloperidol plus promethazine for psychosis-induced aggression., Data Collection and Analysis: We independently extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE., Main Results: We found two new randomised controlled trials (RCTs) from the 2015 update searching. The review now includes six studies, randomising 1367 participants and presenting data relevant to six comparisons.When haloperidol plus promethazine was compared with haloperidol alone for psychosis-induced aggression for the outcome not tranquil or asleep at 30 minutes, the combination treatment was clearly more effective (n=316, 1 RCT, RR 0.65, 95% CI 0.49 to 0.87, high-quality evidence). There were 10 occurrences of acute dystonia in the haloperidol alone arm and none in the combination group. The trial was stopped early as haloperidol alone was considered to be too toxic.When haloperidol plus promethazine was compared with olanzapine, high-quality data showed both approaches to be tranquillising. It was suggested that the combination of haloperidol plus promethazine was more effective, but the difference between the two approaches did not reach conventional levels of statistical significance (n=300, 1 RCT, RR 0.60, 95% CI 0.22 to 1.61, high-quality evidence). Lower-quality data suggested that the risk of unwanted excessive sedation was less with the combination approach (n=116, 2 RCTs, RR 0.67, 95% CI 0.12 to 3.84).When haloperidol plus promethazine was compared with ziprasidone all data were of lesser quality. We identified no binary data for the outcome tranquil or asleep. The average sedation score (Ramsay Sedation Scale) was lower for the combination approach but not to conventional levels of statistical significance (n=60, 1 RCT, MD -0.1, 95% CI - 0.58 to 0.38). These data were of low quality and it is unclear what they mean in clinical terms. The haloperidol plus promethazine combination appeared to cause less excessive sedation but again the difference did not reach conventional levels of statistical significance (n=111, 2 RCTs, RR 0.30, 95% CI 0.06 to 1.43).We found few data for the comparison of haloperidol plus promethazine versus haloperidol plus midazolam. Average Ramsay Sedation Scale scores suggest the combination of haloperidol plus midazolam to be the most sedating (n=60, 1 RCT, MD - 0.6, 95% CI -1.13 to -0.07, low-quality evidence). The risk of excessive sedation was considerably less with haloperidol plus promethazine (n=117, 2 RCTs, RR 0.12, 95% CI 0.03 to 0.49, low-quality evidence). Haloperidol plus promethazine seemed to decrease the risk of needing restraints by around 12 hours (n=60, 1 RCT, RR 0.24, 95% CI 0.10 to 0.55, low-quality evidence). It may be that use of midazolam with haloperidol sedates swiftly, but this effect does not last long.When haloperidol plus promethazine was compared with lorazepam, haloperidol plus promethazine seemed to more effectively cause sedation or tranquillisation by 30 minutes (n=200, 1 RCT, RR 0.26, 95% CI 0.10 to 0.68, high-quality evidence). The secondary outcome of needing restraints or seclusion by 12 hours was not clearly different between groups, with about 10% in each group needing this intrusive intervention (moderate-quality evidence). Sedation data were not reported, however, the combination group did have less 'any serious adverse event' in 24-hour follow-up, but there were not clear differences between the groups and we are unsure exactly what the adverse effect was. There were no deaths.When haloperidol plus promethazine was compared with midazolam, there was clear evidence that midazolam is more swiftly tranquillising of an aggressive situation than haloperidol plus promethazine (n=301, 1 RCT, RR 2.90, 95% CI 1.75 to 4.8, high-quality evidence). On its own, midazolam seems to be swift and effective in tranquillising people who are aggressive due to psychosis. There was no difference in risk of serious adverse event overall (n=301, 1 RCT, RR 1.01, 95% CI 0.06 to 15.95, high-quality evidence). However, 1 in 150 participants allocated haloperidol plus promethazine had a swiftly reversed seizure, and 1 in 151 given midazolam had swiftly reversed respiratory arrest., Authors' Conclusions: Haloperidol plus promethazine is effective and safe, and its use is based on good evidence. Benzodiazepines work, with midazolam being particularly swift, but both midazolam and lorazepam cause respiratory depression. Olanzapine intramuscular and ziprasidone intramuscular do seem to be viable options and their action is swift, but resumption of aggression with subsequent need to re-inject was more likely than with haloperidol plus promethazine. Haloperidol used on its own without something to offset its frequent and serious adverse effects does seem difficult to justify.

Introduction: The Emergency Department Safety Assessment and Follow-up Evaluation Screening Outcome Evaluation examined whether universal suicide risk screening is feasible and effective at improving suicide risk detection in the emergency department (ED)., Methods: A three-phase interrupted time series design was used: Treatment as Usual (Phase 1), Universal Screening (Phase 2), and Universal Screening + Intervention (Phase 3). Eight EDs from seven states participated from 2009 through 2014. Data collection spanned peak hours and 7 days of the week. Chart reviews established if screening for intentional self-harm ideation/behavior (screening) was documented in the medical record and whether the individual endorsed intentional self-harm ideation/behavior (detection). Patient interviews determined if the documented intentional self-harm was suicidal. In Phase 2, universal suicide risk screening was implemented during routine care. In Phase 3, improvements were made to increase screening rates and fidelity. Chi-square tests and generalized estimating equations were calculated. Data were analyzed in 2014., Results: Across the three phases (N=236,791 ED visit records), documented screenings rose from 26% (Phase 1) to 84% (Phase 3) (χ(2) [2, n=236,789]=71,000, p<0.001). Detection rose from 2.9% to 5.7% (χ(2) [2, n=236,789]=902, p<0.001). The majority of detected intentional self-harm was confirmed as recent suicidal ideation or behavior by patient interview., Conclusions: Universal suicide risk screening in the ED was feasible and led to a nearly twofold increase in risk detection. If these findings remain true when scaled, the public health impact could be tremendous, because identification of risk is the first and necessary step for preventing suicide., Trial Registration: Emergency Department Safety Assessmentand Follow-up Evaluation (ED-SAFE) ClinicalTrials.gov: (NCT01150994). https://clinicaltrials.gov/ct2/show/NCT01150994?term=ED-SAFE&rank=1., (Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The main objective was to identify which patient characteristics have the strongest association with suicide outcomes in the 12 months after an index emergency department (ED) visit., Methods: Data were analyzed from the first two phases of the Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE). The ED-SAFE study, a quasi-experimental, interrupted time-series design, involved participation from eight general medical EDs across the United States. Participants included adults presenting to the ED with active suicidal ideation or an attempt in the past week. Data collection included baseline interview; six- and 12-month chart reviews; and six-, 12-, 24-, 36-, and 52-week telephone follow-up assessments. Regression analyses were conducted., Results: Among 874 participants, the median age was 37 years (interquartile range 27-47), with 56% of the sample being female (N=488), 74% white (N=649), and 13% Hispanic (N=113). At baseline, 577 (66%) participants had suicidal ideation only, whereas 297 (34%) had a suicide attempt in the past week. Data sufficient to determine outcomes were available for 782 (90%). In the 12 months after the index ED visit, 195 (25%) had documentation of at least one suicide attempt or suicide. High school education or less, an ED visit in the preceding six months, prior nonsuicidal self-injury, current alcohol misuse, and suicidal intent or plan were predictive of future suicidal behavior., Conclusions: Continuing to build an understanding of the factors associated with future suicidal behaviors for this population will help guide design and implementation of improved suicide screening and interventions in the ED and better allocation of scarce resources., Competing Interests: The authors have no conflicts of interest to report. None of the authors have financial conflicts of interest to disclose.

Background: Psychomotor agitation is associated with different psychiatric conditions and represents an important issue in psychiatry. Current recommendations on agitation in psychiatry are not univocal. Actually, an improper assessment and management may result in unnecessary coercive or sedative treatments. A thorough and balanced review plus an expert consensus can guide assessment and treatment decisions., Methods: An expert task force iteratively developed consensus using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new, re-worded or re-rated items., Results: Out of 2175 papers assessing psychomotor agitation, 124 were included in the review. Each component was assigned a level of evidence. Integrating the evidence and the experience of the task force members, a consensus was reached on 22 statements on this topic., Conclusions: Recommendations on the assessment of agitation emphasise the importance of identifying any possible medical cause. For its management, experts agreed in considering verbal de-escalation and environmental modification techniques as first choice, considering physical restraint as a last resort strategy. Regarding pharmacological treatment, the "ideal" medication should calm without over-sedate. Generally, oral or inhaled formulations should be preferred over i.m. routes in mildly agitated patients. Intravenous treatments should be avoided.

Caspase recruitment family member 14 (CARD14, also known as CARMA2), is a scaffold protein that mediates NF-κB signal transduction in skin keratinocytes. Gain-of-function CARD14 mutations have been documented in familial forms of psoriasis vulgaris (PV) and pityriasis rubra pilaris (PRP). More recent investigations have also implicated CARD14 in the pathogenesis of pustular psoriasis. Follow-up studies, however, have been limited, so that it is not clear to what extent CARD14 alleles account for the above conditions. Here, we sought to address this question by carrying out a systematic CARD14 analysis in an extended patient cohort (n=416). We observed no disease alleles in subjects with familial PV (n=159), erythrodermic psoriasis (n=23), acral pustular psoriasis (n=100), or sporadic PRP (n=29). Conversely, our analysis of 105 individuals with generalized pustular psoriasis (GPP) identified a low-frequency variant (p.Asp176His) that causes constitutive CARD14 oligomerization and shows a significant association with GPP in Asian populations (P=8.4×10(-5); odds ratio=6.4). These data indicate that the analysis of CARD14 mutations could help stratify pustular psoriasis cohorts but would be mostly uninformative in the context of psoriasis and sporadic PRP.

Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genome-wide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype calling and imputation and by the addition of 5,033 cases and 5,707 controls. The combined analysis, consisting of over 15,000 cases and 27,000 controls, identifies five new psoriasis susceptibility loci at genome-wide significance (P<5 × 10(-8)). The newly identified signals include two that reside in intergenic regions (1q31.1 and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3) and CAMK2G (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2-dependent target of IL-17 signalling in human skin keratinocytes, thereby functionally linking two strong candidate genes. These results further integrate the genetics and immunology of psoriasis, suggesting new avenues for functional analysis and improved therapies.

This study evaluated the concurrent validity of a brief suicide risk screener for adults in the emergency department (ED). Two versions of the verbally administered Patient Safety Screener (2-item, 3-item) were compared to a reference standard, the Beck Scale for Suicide Ideation (BSSI). Analyses included measures of agreement (Kappa). Agreement between the Patient Safety Screener-2 and -3 and the BSSI (n = 951) was almost perfect for overall positive screening (K = 0.94-0.95) and past suicide attempts (K = 0.97-0.98). Agreement on ideation ranged from fair (K = 0.34) for the 2-item version to good (K = 0.61) for the 3-item version. The Patient Safety Screener's concurrent validity with the BSSI ranged from fair to almost perfect and warrants additional study.

Bis(diphenylphosphino)alkanes quantitatively react with excess 1-bromododecane to prepare novel phosphonium gemini surfactants with spacer lengths ranging from 2 to 4 methylenes (12-2/3/4-12P). Dodecyltriphenylphosphonium bromide (DTPP), a monomeric surfactant analog, was readily water soluble, however, in sharp contrast, phosphonium gemini surfactants were poorly soluble in water due to two hydrophobic tails and relatively hydrophobic cationic head groups containing phenyl substituents. Isothermal titration calorimetry did not reveal a measurable critical micelle concentration for the 12-2-12P phosphonium gemini surfactant in water at 25 °C. Subsequent studies in 50/50 v/v water-methanol at 25 °C showed a CMC of 1.0 mM for 12-2-12P. All phosphonium gemini surfactants effectively complexed nucleic acids, but failed to deliver nucleic acids in vitro to HeLa cells. The solution behavior of phosphonium gemini surfactants was investigated in chloroform, which is an organic solvent where reverse micellar structures are favored. Solution rheology in chloroform explored the solution behavior of the phosphonium gemini surfactants compared to DTPP. The 12-2-12P and 12-3-12P gemini surfactants were successfully electrospun from chloroform to generate uniform fibers while 12-4-12P gemini surfactant and DTPP only electrosprayed to form droplets.

Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis., (Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)