Enhancing patient safety in psychiatric settings

OBJECTIVE: There is growing national consensus that use of institutional measures of control, such as seclusion, restraint, enforced medications, and hand-cuffed transport, within psychiatric hospitals is all too common and is potentially counter-therapeutic. Unfortunately, little is known about how to reduce such measures of last resort. This article reviews the available literature and describes a proposed research agenda involving a behavioral effort, the Engagement Model, for reducing seclusion and restraint procedures and enhancing patient safety in psychiatric settings. METHODS: Using Medline and PsychInfo, we reviewed studies that specifically evaluated efforts to reduce seclusion and restraint on psychiatric units. Key search terms included seclusion, restraint, reduc*, psychiatric patient safety, psychiatric safety, psychiatric sanctuary, and quality of care psychiatry. RESULTS: Only very limited data are available on reducing measures of last resort and improving the safety of psychiatric settings, and virtually no controlled data are available concerning the effectiveness of specific behavioral efforts on subsequent reduction of seclusion and restraint events. In light of the paucity of data, we describe efforts to incorporate and evaluate such a model in a large academic psychiatric hospital using a multiple baseline times-series design and review principles for and obstacles to implementing this model. CONCLUSIONS: It is hoped this discussion will stimulate research on this understudied topic and provide a framework for improving patient safety in psychiatric settings.     

Identification of citrullinated vimentin peptides as T cell epitopes in HLA–DR4–positive patients with rheumatoid arthritis

Objective

Antibodies directed against citrullinated proteins (ACPAs) are highly specific for rheumatoid arthritis (RA). The production of ACPAs is most likely dependent on the presence of T cells, since ACPAs undergo isotype switching and are associated with the shared epitope (SE)–containing HLA–DRB1 alleles. Vimentin is a likely candidate protein for T cell recognition, since >90% of patients positive for ACPAs that are reactive with (peptides derived from) citrullinated vimentin carry SE‐containing HLA–DRB1 alleles. The aim of this study was to identify citrullinated vimentin peptides that are presented to HLA–DRB1*0401–restricted T cells.

Methods

HLA–DR4–transgenic mice were immunized with all possible citrulline‐containing peptides derived from vimentin, and T cell reactivity was analyzed. Peptides recognized in a citrulline‐specific manner by T cells were selected and analyzed for their ability to be processed from the entire vimentin protein. A first inventory of the selected epitopes recognized by T cells was performed using peripheral blood mononuclear cells (PBMCs) from ACPA+, HLA–DR4+ patients with RA.

Results

A citrulline‐specific response was observed for 2 of the peptides analyzed in DR4‐transgenic mice. These peptides were found to be naturally processed from the vimentin protein, since citrullinated vimentin was recognized by peptide‐specific T cells. T cell reactivity against these peptides was also observed in cultures of PBMCs from RA patients.

Conclusion

This study identifies, for the first time, 2 naturally processed peptides from vimentin that are recognized by HLA–DRB1*0401–restricted T cells in a citrulline‐specific manner. These peptides can be recognized by T cells in ACPA+, HLA–DR4+ patients with RA, as shown in a first inventory.

     

Cognitive vulnerability in fear of flying: the role of anxiety sensitivity

Previous research has indicated that more than 50% of air travel passengers experience hypoxia above clinical threshold. This condition produces a number of aversive somatic sensations such as difficulty breathing, elevated heart rate, dizziness, etc. Because these symptoms closely resemble the somatic symptoms of anxiety, it is interesting to look into a possible relationship between hypoxia-related symptoms and fear of flying. More specifically, the aim of this study is to clarify the role of anxiety sensitivity as a cognitive vulnerability marker in this relationship. Anxiety sensitivity is the specific tendency to interpret bodily sensations as threatening or harmful. Our hypothesis is that anxiety sensitivity moderates the relationship between hypoxia-related symptoms and fear of flying. When people with high anxiety sensitivity fly and experience somatic symptoms, they will make threatening interpretations causing fear and as a possible consequence avoidance behaviour leading to flight anxiety. About 160 participants were asked to complete the Flight Anxiety Situations Questionnaire, the Flight Anxiety Modality Questionnaire and the Anxiety Sensitivity Index. Results of a moderator analysis indicated that the relationship between somatic sensations and in-flight anxiety is stronger for people with high anxiety sensitivity than for people with low anxiety sensitivity. So it seems that anxiety sensitivity does indeed function as a moderator between the experience of somatic sensations while flying and in-flight anxiety. Clinical implications are discussed, as well as suggestions for further research.     

The PTSD symptom scale's latent structure: an examination of trauma-exposed medical patients

Several studies have employed confirmatory factor analysis (CFA) to evaluate the latent structure of posttraumatic stress disorder (PTSD) assessment measures among various trauma-exposed populations. Findings have generally failed to support the current three-factor DSM-IV PTSD conceptualization, demonstrating the need to consider alternative models. The present study used CFA to evaluate seven models, including intercorrelated and hierarchical versions of two models with the most empirical support. Data were utilized from a heterogeneous trauma-exposed sample of general medical patients (n=252). Based on several indices, the three-factor DSM-IV PTSD model was shown to be inferior to alternative models. The strongest support was found for an intercorrelated four-factor model, separating avoidance and numbing symptoms into distinct factors. Validity for this model was partially supported by divergent relations between factors and external variables. Implications of the results are discussed, and a framework is proposed for resolving discrepant findings in the PTSD CFA literature.     

Self-referred paediatric patients with abnormal vital signs only seen by an emergency physician,are we missing severe ill patients?

Tijdschrift voor Kindergeneeskunde -     

EORTC 26083 phase I/II trial of dasatinib in combination with CCNU in patients with recurrent glioblastoma

The treatment of patients with recurrent glioblastoma remains a major oncologic problem, with median survival after progression of 7–9 months. To determine the maximum tolerated dose and dose-limiting toxicity (DLT), the combination of dasatinib and cyclonexyl-chloroethyl-nitrosourea (CCNU) was investigated in this setting. The study was designed as multicenter, randomized phase II trial, preceded by a lead-in safety phase. The safety component reported here, which also investigated pharmacokinetics and preliminary clinical activity, required expansion and is therefore considered a phase I part to establish a recommended dosing regimen of the combination of CCNU (90–110 mg/m²) and dasatinib (100–200 mg daily). Overall, 28 patients were screened, and 26 patients were enrolled. Five dose levels were explored. DLTs, mainly myelosuppression, occurred in 10 patients. Grade 3 or 4 neutropenia was recorded in 7 patients (26.9%) and thrombocytopenia in 11 patients (42.3%). No significant effect of CCNU coadministration on dasatinib pharmacokinetics was found. Median progression-free survival (PFS) was 1.35 months (95% confidence interval: 1.2–1.4) and 6-month PFS was 7.7%. In this phase I study of recurrent glioblastoma patients, the combination of CCNU and dasatinib showed significant hematological toxicities and led to suboptimal exposure to both agents.     

Aging affects the ability to use optic flow in the control of heading during locomotion

Perceived self-motion from optic flow is implicated in the control of locomotion. Aging, which affects visual perception and sensorimotor integration, may result in an inability to use optic flow to guide heading while walking. The purpose of this study was to examine whether advanced age could impact on the steering of locomotion, when changing optic flow directions were presented in an immersive virtual environment (VE). Nine young adults (21.56 ± 3.20 years) and nine older adults (66.11 ± 3.95 years) participated in the study. Subjects were asked to walk while viewing a VE through a head-mounted display unit (Kaiser). The VE viewed by the subjects was a large room displayed as an expanding translational optic flow, with the focus of expansion (FOE) located at neutral, 20° or 40° to the right or left. Their task was to walk straight with respect to the VE. Kinematic data in 3D were collected, from which the body’s centre of mass (CoM) position and heading direction were calculated. Young subjects were able to make proper heading adjustments in the VE, with respect to FOE shifts, but not older individuals. Young subjects altered their CoM trajectory so that it was oriented in the direction opposite to the FOE in the physical environment and resulted in small deviation in the VE. The older adults did not adjust their locomotor patterns in response to the different flows presented and maintained similar walking trajectories across all trials. Advanced age results in an altered control of steering of locomotion in response to changing directions of optic flow. This may be related to an impaired perception and/or use of the optic flow, or due to inherent problems in sensorimotor integration.