Search

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.

Sulfonium macromolecules displayed for the first time nucleic acid binding and transfection in vitro. Conventional and controlled radical polymerization techniques coupled with subsequent alkylation generated a sulfonium homopolymer, poly(DMSEMA), and a sulfonium diblock copolymer, poly(OEG-b-DMSEMA). DNA gel shift assays probed the ability of sulfonium macromolecules to complex nucleic acids, and luciferase assays examined the transfection efficiency and cytotoxicity of both sulfonium macromolecules. Poly(DMSEMA) and poly(OEG-b-DMSEMA) bound pDNA at a charge ratio of 1, and both induced significant luciferase expression in HeLa cells under serum-free conditions. Colloidal stability studies using dynamic light scattering highlighted the excellent colloidal stability of poly(OEG-b-DMSEMA) under salt and serum conditions due to the sterically stabilizing OEG block. Sulfonium macromolecules offer an alternate route to design cationic macromolecules for nonviral nucleic acid delivery, and future work will aim...

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.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.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.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.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.

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).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.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.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.

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.

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.

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.

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

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.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.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.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.

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.

It is estimated that emergency departments (EDs) could prevent 5% of all suicide attempts and 8% of suicide deaths, making EDs a critical setting in which to identify individuals at risk for suicide and to intervene to mitigate the risk. The goal of this review was to detail recent advances in the identification, assessment, and management of suicide risk in emergency medicine and to provide best practice recommendations for these processes. Advances in caring for patients who present to EDs with suicide risk include improved workflows and tools for ED providers to identify, assess, and manage suicide risk, increased patient-centeredness and quality of ED care for patients at risk of suicide, and shifting beliefs of ED providers regarding the feasibility of integrating the assessment and management of suicide risk into emergency care. ED suicide prevention efforts have notably changed in recent years. Strategies for universal screening, secondary screening tools, and evidence-based workflows for the management of suicide risk all show potential for feasibly addressing suicide risk in EDs. Effective implementation of evidence-based practices is necessary as integrating these new practices requires significant change in the clinical practice and culture of many EDs.

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.

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.

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.

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. Acne vulgaris is a chronic inflammation of the skin, the genetic basis of which is incompletely understood. Here, Petridis et al. perform GWAS and meta-analysis for acne in 26,722 individuals and identify 12 novel risk loci that implicate structure and maintenance of the skin in severe acne risk.

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.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.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.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.

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.

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.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.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.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.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.

Novel trialkylphosphonium ionic liquids chain extenders enabled the successful synthesis of poly(ethylene glycol)-based, cationic polyurethanes with pendant phosphoniums in the hard segments (HS). Aqueous size exclusion chromatography (SEC) confirmed the charged polyurethanes, which varied the phosphonium alkyl substituent length (ethyl and butyl) and cationic HS content (25, 50, 75 mol%), achieved high absolute molecular weights. Dynamic mechanical analysis (DMA) demonstrated the triethylphosphonium (TEP) and tributylphosphonium (TBP) polyurethanes displayed similar thermomechanical properties, including increased rubbery plateau moduli and flow temperatures. Fourier transform infrared spectroscopy (FTIR) emphasized the significance of ion–dipole interaction on hydrogen bonding. Atomic force microscopy (AFM), small-angle X-ray scattering (SAXS), and wide-angle X-ray diffraction (WAXD) supported microphase separated morphologies in the trialkylphosphonium polyurethanes, despite the presence of ionic interactions. Sorption isotherm experiments revealed the TEP polyurethane exhibited the highest water vapor sorption profile compared to the TBP, which displayed similar water sorption profiles to the noncharged analogue. The phosphonium polyurethanes displayed significantly improved tensile strain; however, lower tensile stress of the TEP polyurethane was presumably due to absorbed water. In addition to physical characterizations, we also explored the trialkylphosphonium polyurethanes as nucleic acid delivery vectors. The phosphonium polyurethanes bound DNA at low charge ratios, and the polyplexes exhibited enhanced colloidal stability under physiological salt conditions.

Psychomotor agitation is often associated with aggression. It is important to identify agitation early and achieve results quickly in order to prevent aggressive behavior. Strategies may include verbal de-escalation techniques, reduced stimulation, medications, or a combination of approaches. Historically, pharmacological treatments for agitation have been delivered using oral and intramuscular formulations. Although the types of medication available have not changed dramatically, different formulations have been developed recently to aid in treating this difficult condition. This paper will detail some of the newer, more novel formulations used to deliver medications to treat agitation. Formulations to be described include orally disintegrating tablets, sublingual, buccal and intranasal forms, as well as an inhalation form. Each form has a unique purpose and will aid in treatment of different populations at different levels of agitation. Of note, of the medication formulations to be discussed, only inhaled loxapine is FDA approved for acute agitation in schizophrenia and bipolar disorder and no medications are approved for 'agitation' outside of a specific disease state. The orally disintegrating tablets of olanzapine, risperidone, and aripiprazole are swallowed and enter the circulation via the portal system. They do not have a more rapid onset of action than the standard oral tablets but are useful for patients that might otherwise divert the medication. The sublingual, buccal and intranasal formulations include asenapine and midazolam. Absorption by this route is more rapid and avoids first-pass metabolism. Finally, inhaled loxapine enters the alveoli and appears quickly in the arterial circulation. All of these novel formulations require at least some cooperation but have the potential to prevent escalation and improve the experience of patients and could be considered when negotiation is possible.

Conventional free radical polymerization of (hydroxy)alkyl-containing vinylimidazolium ionic liquid monomers generated high molecular weight polymers. A study of these materials was undertaken to relate chemical composition to macromolecular properties. Varying the substituent chain length and functionality of these polymerized ionic liquids (PILs) significantly influenced numerous polymer properties. Incorporation of a hydroxyl group at the terminus of the alkyl substituent lowered the glass transition temperature (Tg) of the PILs ∼50 °C and increased homopolymer thermal stability compared to the respective alkyl analogue. X-ray scattering demonstrated that (hydroxy)alkyl chain length influenced polymer backbone-to-backbone spacing. More importantly, X-ray scattering showed hydroxyl incorporation diminished the local compositional heterogeneity present in the alkyl-functionalized vinylimidazolium homopolymers. Solid-state NMR quantified ratios of locally ordered versus disordered components. Ionic conduc...

Joint Commission National Patient Safety Goal 15 calls for organizations "to identify patients at risk for suicide." Overt suicidal behavior accounts for 0.6% of emergency department (ED) visits, but incidental suicidal ideation is found in 3%-11.6%. This is the first multicenter study of suicide screening in EDs. Of 2,243 patients in six diverse emergency settings, 1,068 (47.7%) were screened with a brief instrument. Depression was endorsed by 369 (34.5%); passive suicidal ideation by 79 (7.3%); and active suicidal ideation by 24 (2.3%). One hundred thirty-seven (12.8%) reported prior attempts, including 35 (3.3%) with current suicidal ideation. Almost half of those with current ideation had a prior attempt (43.8%) versus those without current ideation, 10.3%, χ2 (1) = 75.59, p < .001. Twenty cases (25%) were admitted to medical services, but only 10 (12.5%) received mental health assessment; none were admitted directly to a psychiatry service. The prevalence of suicidal ideation here is similar to previous studies but the frequency of prior attempts has not been reported. The 35 cases with current ideation and prior attempt are at risk. As they did not present psychiatrically, they would likely have gone undetected. Despite reporting these cases to clinical staff, few received risk assessment.

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.

This post hoc analysis evaluated the effect of lurasidone on agitation in acutely ill patients with schizophrenia.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.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; p0.05), Day 7 (-2.3 vs -1.6; p0.05), and at Week 6 endpoint (-5.5 vs -3.8; p0.001; effect size=0.43). In patients with lower agitation at baseline (PANSS-EC score14; n=754), LS mean PANSS-EC score change was significantly greater for lurasidone compared with placebo at Day 7 (-0.8 vs -0.1; p0. 01) through Week 6 endpoint (-1.9 vs -0.9; p0.001; effect size=0.31). Higher doses of lurasidone were notably more effective than lower doses in patients with more severe agitation at study baseline.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.

We examined whether caregivers of bipolar patients reporting current suicidal ideation and/or a history of a suicide attempt reported higher levels of burden and/or poorer health compared to caregivers of patients without these suicidality indices. In a cross-sectional design, caregivers (N = 480) associated with (a) patients with current suicidal ideation or (b) patients with a positive lifetime history of at least one suicide attempt, reported lower general health scores than caregivers associated with patients with neither of these indices. Parents of patients with at least one lifetime attempt reported more burden secondary to role dysfunction than spouses. Levels of depression in caregivers varied with whether the caregiver was a spouse or a parent, and whether patients had a history of suicide attempts, current suicidal ideation, or both.

BACKGROUND: Episodes of depression are the most frequent cause of disability among patients with bipolar disorder. The effectiveness and safety of standard antidepressant agents for depressive episodes associated with bipolar disorder (bipolar depression) have not been well studied. Our study was designed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania. METHODS: In this double-blind, placebo-controlled study, we randomly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo, under conditions generalizable to routine clinical care. A standardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, was used at all follow-up visits. The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery (8 consecutive weeks of euthymia). Secondary effectiveness outcomes and rates of treatment-emergent affective switch (a switch to mania or hypomania early in the course of treatment) were also examined. RESULTS: Forty-two of the 179 subjects (23.5%) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery, as did 51 of the 187 subjects (27.3%) receiving a mood stabilizer plus a matching placebo (P=0.40). Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes. Rates of treatment-emergent affective switch were similar in the two groups. CONCLUSIONS: The use of adjunctive, standard antidepressant medication, as compared with the use of mood stabilizers, was not associated with increased efficacy or with increased risk of treatment-emergent affective switch. Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder. (ClinicalTrials.gov number, NCT00012558 [ClinicalTrials.gov].).

OBJECTIVE: In a naturalistic follow-up of adult bipolar patients, the authors examined the contributions of demographic, phenomenological, and clinical variables, including antidepressant use, to prospectively observed mood episode frequency. METHOD: For 1,742 bipolar I and II patients in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), episodes of mood disorders were evaluated for up to 1 year of treatment. RESULTS: At entry, 32% of the patients met the DSM-IV criteria for rapid cycling in the prestudy year. Of the 1,742 patients, 551 (32%) did not complete 1 year of treatment. Among the 1,191 patients remaining, those with prior rapid cycling (N=356) were more likely to have further recurrences, although not necessarily more than four episodes per year. At the end of 12 months, only 5% (N=58) of the patients could be classified as rapid cyclers; 34% (N=409) had no further mood episodes, 34% (N=402) experienced one episode, and 27% (N=322) had two or three episodes. Patients who entered the study with earlier illness onset and greater severity were more likely to have one or more episodes in the prospective study year. Antidepressant use during follow-up was associated with more frequent mood episodes. CONCLUSIONS: While DSM-IV rapid cycling was prospectively observed in only a small percentage of patients, the majority of these patients had continued recurrences at lower but clinically significant rates. This suggests that cycling is on a continuum and that prevention of recurrences may require early intervention and restricted use of antidepressants.

The pathogenesis of bipolar disorder may involve, at least in part, aberrations in serotonergic neurotransmission. Hence, serotonergic genes are attractive targets for association studies of bipolar disorder. We have reviewed the literature in this field. It is difficult to synthesize results as only one polymorphism per gene was typically investigated in relatively small samples. Nevertheless, suggestive associations are available for the 5HT2A receptor and the serotonin transporter genes. With the availability of extensive polymorphism data and high throughput genotyping techniques, comprehensive evaluation of these genes using adequately powered samples is warranted. We also report on our investigations of the serotonin transporter, SLC6A4 (17q11.1-q12). An insertion/deletion polymorphism (5HTTLPR) in the promoter region of this gene has been investigated intensively. However, the results have been inconsistent. We reasoned that other polymorphism/s may contribute to the associations and the inconsistencies may be due to variations in linkage disequilibrium (LD) patterns between samples. Therefore, we conducted LD analyses, as well as association and linkage using 12 polymorphisms, including 5HTTLPR. We evaluated two samples. The first sample consisted of 135 US Caucasian nuclear families having a proband with bipolar I disorder (BDI, DSM IV criteria) and available parents. For case-control analyses, the patients from these families were compared with cord blood samples from local Caucasian live births (n = 182). Our second, independent sample was recruited through the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD, 545 cases, 548 controls). No significant associations were detected at the individual polymorphism or haplotype level using the case-control or family-based analyses. Our analyses do not support association between SLC6A4 and BDI families. Further studies using sub-groups of BDI are worthwhile.

We previously reported genome-wide significant evidence for linkage between chromosome 6q and bipolar I disorder (BPI) by performing a meta-analysis of original genotype data from 11 genome scan linkage studies. We now present follow-up linkage disequilibrium mapping of the linked region utilizing 3,047 single nucleotide polymorphism (SNP) markers in a case–control sample (N = 530 cases, 534 controls) and family-based sample (N = 256 nuclear families, 1,301 individuals). The strongest single SNP result (rs6938431, P = 6.72 × 10−5) was observed in the case–control sample, near the solute carrier family 22, member 16 gene (SLC22A16). In a replication study, we genotyped 151 SNPs in an independent sample (N = 622 cases, 1,181 controls) and observed further evidence of association between variants at SLC22A16 and BPI. Although consistent evidence of association with any single variant was not seen across samples, SNP-wise and gene-based test results in the three samples provided convergent evidence for association with SLC22A16, a carnitine transporter, implicating this gene as a novel candidate for BPI risk. Further studies in larger samples are warranted to clarify which, if any, genes in the 6q region confer risk for bipolar disorder. © 2009 Wiley-Liss, Inc.

OBJECTIVE: The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) is designed to evaluate the longitudinal outcome of patients with bipolar disorder. The STEP-BD disease-management model is built on evidence-based practices and a collaborative care approach designed to maximize specific and nonspecific treatment mechanisms. This prospective study examined the longitudinal relationships between patients' satisfaction with care, levels of hope, and life functioning in the first 1000 patients to enter STEP-BD. METHODS: The study used scores from the Care Satisfaction Questionnaire, Beck Hopelessness Scale, Range of Impaired Functioning Tool, Young Mania Rating Scale, and Montgomery-Asberg Depression Rating Scale at 5 time points during a 1-year interval. Analyses tested mediational pathways between care satisfaction, hope, and life functioning, depression, and mania using mixed-effects (random and fixed) regression models. RESULTS: Increases in care satisfaction were associated with decreased hopelessness (P < .01) but not related to symptoms of depression or mania. Similarly, decreased hopelessness was associated with better life functioning (P < .01) but not related to symptoms of depression or mania. Depression was independently associated with poorer life functioning (P < .0001). CONCLUSIONS: This study provided support for the hypothesized mediational pathway between care satisfaction, hopelessness, and life functioning. Findings suggest that providing care that maximizes patient hope may be important. By so doing, patients might overcome the learned helplessness/hopelessness that often accompanies a cyclical illness and build a realistic illness-management strategy.

RAFT polymerization successfully controlled the synthesis of phosphonium-based AB diblock copolymers for nonviral gene delivery. A stabilizing block of either oligo(ethylene glycol(9)) methyl ether methacrylate or 2-(methacryloxy)ethyl phosphorylcholine provided colloidal stability, and the phosphonium-containing cationic block of 4-vinylbenzyltributylphosphonium chloride induced electrostatic nucleic acid complexation. RAFT polymerization generated well-defined stabilizing blocks (M(n) = 25000 g/mol) and subsequent chain extension synthesized diblock copolymers with DPs of 25, 50, and 75 for the phosphonium-containing block. All diblock copolymers bound DNA efficiently at ± ratios of 1.0 in H(2)O, and polyplexes generated at ± ratios of 2.0 displayed hydrodynamic diameters between 100 and 200 nm. The resulting polyplexes exhibited excellent colloidal stability under physiological salt or serum conditions, and they maintained constant hydrodynamic diameters over 24 h. Cellular uptake studies using Cy5-labeled DNA confirmed reduced cellular uptake in COS-7 and HeLa cells and, consequently, resulted in low transfection in these cell lines. Serum transfection in HepaRG cells, which are a predictive cell line for in vivo transfection studies, showed successful transfection using all diblock copolymers with luciferase expression on the same order of magnitude as Jet-PEI. All diblock copolymers exhibited low cytotoxicity (>80% cell viability). Promising in vitro transfection and cytotoxicity results suggest future studies involving the in vivo applicability of these phosphonium-based diblock copolymer delivery vehicles.

We report the unprecedented controlled radical polymerization of 4-vinylimidazole (4VIM). Reversible addition–fragmentation chain transfer (RAFT) of 4VIM in glacial acetic acid afforded homopolymers with well-defined molecular weights and narrow polydispersity indices (PDIs). The polymerizations in acetic acid mediated with 4-cyano-4-(ethylsulfanylthiocarbonylsulfanyl)pentanoic acid (CEP) displayed linear pseudo-first-order kinetics and linear molecular weight growth with monomer conversion. Systematic variation of numerous polymerization parameters included solvent composition, initiator concentration, monomer concentration, and the calculated degree of polymerization. Aqueous size exclusion chromatography (SEC) confirmed linear molecular weight growth to number-average molecular weights (Mn) of 65 000 g/mol with low PDIs (

There are twice as many suicides as homicides in the United States, and the suicide rate is rising. Suicides increased 12% between 1999 and 2009. Mental health professionals often treat suicidal patients, and suicide occurs even among patients who are seeking treatment or are currently in treatment. Despite these facts, training of most mental health professionals in the assessment and management of suicidal patients is surprisingly limited. The extant literature regarding the frequency with which mental health professionals encounter suicidal patients is reviewed, as is the prevalence of training in suicide risk assessment and management. Most importantly, six recommendations are made to address the longstanding insufficient training within the mental health professions regarding the assessment and management of suicidal patients.

Kwentus J, Riesenberg RA, Marandi M, Manning RA, Allen MH, Fishman RS, Spyker DA, Kehne JH, Cassella JV. Rapid acute treatment of agitation in patients with bipolar I disorder: a multicenter, randomized, placebo-controlled clinical trial with inhaled loxapine. Bipolar Disord 2012: 14: 31–40. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: The present study evaluated inhaled loxapine for the acute treatment of agitation in patients with bipolar I disorder. Methods: A Phase 3, randomized, double blind, placebo-controlled, parallel group inpatient study was performed at 17 psychiatric research facilities. Agitated patients (N = 314) with bipolar I disorder (manic or mixed episodes) were randomized (1:1:1) to inhaled loxapine 5 mg or 10 mg, or inhaled placebo using the Staccato® system. Following baseline assessments, patients received Dose 1 and were evaluated for 24 hours. If required, up to two additional doses of study drug and/or lorazepam rescue medication were given. The primary efficacy endpoint was change from baseline in the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) score two hours after Dose 1. The key secondary endpoint was the Clinical Global Impression-Improvement score at two hours after Dose 1. Additional endpoints included the changes from baseline in the PANSS-EC from 10 min through 24 hours after Dose 1. Safety was assessed by adverse events, vital signs, physical examinations, and laboratory tests. Results: For the primary and key secondary endpoints, both doses of inhaled loxapine significantly reduced agitation compared with placebo. Reduced agitation, as reflected in PANSS-EC score, was evident 10 min after Dose 1 with both doses. Inhaled loxapine was well tolerated, and the most common adverse events were known effects of loxapine or minor oral effects common with inhaled medications (dysgeusia was reported in 17% of patients receiving active drug versus 6% receiving placebo). Conclusions: Inhaled loxapine provided a rapid, non-injection, well-tolerated acute treatment for agitation in patients with bipolar I disorder.