Dynamics of somatostatin 4 receptor expression during chronic-stress loading and its potential as a chronic-stress marker.

Chronic stress has been implicated in mental illnesses and depressive behaviors. Somatostatin 4 receptor (SSTR4) has been shown to mediate anxiolytic and depression-like effects. Here, we aimed to explore the potential of SSTR4 as a diagnostic marker for chronic stress in mice. The mice were divided into single stress, chronic restraint stress, and control groups, and Sstr4 mRNA expression in the pituitary, lungs, and thymus, its protein expression in the thymus, were analyzed. Compared to controls, Sstr4 mRNA expression decreased significantly in the pituitary gland of the chronic and single-stress groups (P = 0.0181 and 0.0022, respectively) and lungs of the single-stress group (P = 0.0124), whereas it significantly increased in the thymus of the chronic-stress group (P = 0.0313). Thymic SSTR4 expression did not decrease significantly in stress groups compared to that in the control group (P = 0.0963). These results suggest that SSTR4 expression fluctuates in response to stress. Furthermore, Sstr4 mRNA expression dynamics in each organ differed based on single or chronic restraint stress-loading periods. In conclusion, this study suggests that investigating SSTR4 expression in each organ could allow for its use as a stress marker to estimate the stress-loading period and aid in diagnosing chronic stress.

Coprococcus eutactus screened from healthy adolescent attenuates chronic restraint stress-induced depression-like changes in adolescent mice: Potential roles in the microbiome and neurotransmitter modulation.

The onset of depression commonly occurs in adolescence; therefore, depressive prevention and intervention are pivotal during this period. It is becoming evident that neurotransmitter imbalance and gut microbiota dysbiosis are prominent causes of depression. However, the underlying links and mechanisms remain poorly understood. In this study, with 16S ribosomal RNA gene sequencing, genus Coprococcus markedly differentiated between the healthy and unmedicated depressive adolescents. Based on this, transplantation of Coprococcus eutactus (C.e.) was found to dramatically ameliorate the chronic restraint stress (CRS) induced depression-like changes and prevent synaptic loss and glial-stimulated neuroinflammation in mice. The Ultra-high performance liquid chromatography tandem mass spectrometry analysis (UHPLC-MS/MS) further showed that neurotoxic neurotransmitters in kynurenine pathway (KP) such as 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HAA) decreased in mouse brains, mechanistically deciphering the transfer of the tryptophan metabolic pathway to serotonin metabolic signaling in the brain after C.e. treatment, which was also verified in the colon. Molecularly, blockage of KP activities mediated by C.e. was ascribed to the restraint of the limit-step enzymes responsible for kynurenine, 3-HK, and quinolinic acid generation. In the colon, C.e. treatment significantly recovered goblet cells and mucus secretion in CRS mice which may ascribe to the rebalance of the disordered gut microbiota, especially Akkermansia, Roseburia, Rikenella, Blautia, and Alloprevotella. Taken together, the current study reveals for the first time the beneficial effects and potential mechanisms of C.e. in ameliorating CRS-induced depression, unraveling the direct links between C.e. treatment and neurotransmitter rebalance, which may provide efficacious therapeutic avenues for adolescent depressive intervention.

[Ethics of care: Assessment of the ethical issues in the protocols or consensuses on mechanical restraint in force in Spain]. / Ética de los cuidados: valoración de los contenidos éticos en los protocolos o consensos de contención mecánica vigentes en España.

INTRODUCTION: Mechanical restraints are widely used in health care practice, despite the numerous ethical conflicts they raise. The aim of this study is to evaluate the ethical considerations contemplated in the current protocols on mechanical restraint in Spain. METHOD: Systematic review in PubMed, WOS and Scopus, Google and Google Scholar. An ad hoc list of 30 items was used to evaluate the ethical content of the protocols. The quality of guidelines was assessed with AGREE II. RESULTS: The need for informed consent (IC) is reflected in 72% of the documents, the IC model sheet is included in only 41% of them, the rest of the analyzed characteristics on IC are fulfilled in percentages between 6% (the document includes the need to reevaluate the indication for IC) and 31% (the document contemplates to whom it should be requested). More than 20 ethical contents are reflected in 31% of them and less than 10 in 19% of the guidelines. The quality of the guides, according to AGREE II, ranged from 27 to 116 points (maximum possible 161), with a mean score of 68.7. Only 9% of the documents were classified as high quality. Finally, the correlation between ethical content and quality measured with AGREE II was 0.75. CONCLUSIONS: The variability of ethical contents in guidelines on mechanical restraints is very high. The ethical requirements to be included in protocols, consensus or Clinical Practice Guidelines should be defined.

The Present Legal Status Regarding the Utilization of Mechanical or Pharmacological Restraints in Psychiatric and Social-Health Settings.

No abstract present.

Use of Electronic Health Record-Based Measures to Assess Quality of Care for Pediatric Agitation.

OBJECTIVES: Acute agitation during pediatric mental health emergency department (ED) visits presents safety risks to patients and staff. We previously convened multidisciplinary stakeholders who prioritized 20 proposed quality measures for pediatric acute agitation management. Our objectives were to assess feasibility of evaluating performance on these quality measures using electronic health record (EHR) data and to examine performance variation across 3 EDs. METHODS: At a children's hospital and 2 nonchildren's hospitals, we assessed feasibility of evaluating quality measures for pediatric acute agitation management using structured EHR data elements. We retrospectively evaluated measure performance during ED visits by children 5 to 17 years old who presented for a mental health condition, received medication for agitation, or received physical restraints from July 2020 to June 2021. Bivariate and multivariable regression were used to examine measure performance by patient characteristics and hospital. RESULTS: We identified 2785 mental health ED visits, 275 visits with medication given for agitation, and 35 visits with physical restraints. Performance was feasible to measure using EHR data for 10 measures. Nine measures varied by patient characteristics, including 4.87 times higher adjusted odds (95% confidence interval 1.28-18.54) of physical restraint use among children with versus without autism spectrum disorder. Four measures varied by hospital, with physical restraint use varying from 0.5% to 3.3% of mental health ED visits across hospitals. CONCLUSIONS: Quality of care for pediatric acute agitation management was feasible to evaluate using EHR-derived quality measures. Variation in performance across patient characteristics and hospitals highlights opportunities to improve care quality.

Reducing (Behavioral) Restraint Use Through Simulation at the Bedside.

Hospitals are experiencing an influx of patients in active behavioral crises, leading to restraints as a behavior management strategy. Over 100 staff participated in simulation training designed to manage escalating patient behavior. The training had a direct impact on the reduction of restraint use and increased preparedness and confidence of participants managing escalating patient behavior. Results suggest simulation can be an effective strategy to train medical staff to manage challenging behavior and reduce restraint use.

Pediatric Physical Restraint Coding in US Hospitals: A 2019 Kids Inpatient Database Study.

BACKGROUND: Reduction of physical restraint utilization is a goal of high-quality hospital care, but there is little nationally-representative data about physical restraint utilization in hospitalized children in the United States. This study reports the rate of physical restraint coding among hospitalizations for patients aged 1 to 18 years old in the United States and explores associated demographic and diagnostic factors. METHODS: The Kids' Inpatient Database, an all-payors database of community hospital discharges in the United States, was queried for hospitalizations with a diagnosis of physical restraint status in 2019. Logistic regression using patient sociodemographic characteristics was used to characterize factors associated with physical restraint coding. RESULTS: A coded diagnosis of physical restraint status was present for 8893 (95% confidence interval [CI]: 8227-9560) hospitalizations among individuals aged 1 to 18 years old, or 0.63% of hospitalizations. Diagnoses associated with physical restraint varied by age, with mental health diagnoses overall the most frequent in an adjusted model, male sex (adjusted odds ratio [aOR] 1.56; 95% CI: 1.47-1.65), Black race (aOR 1.43; 95% CI: 1.33-1.55), a primary mental health or substance diagnosis (aOR 7.13; 95% CI: 6.42-7.90), Medicare or Medicaid insurance (aOR 1.33; 95% CI: 1.24-1.43), and more severe illness (aOR 2.83; 95% CI: 2.73-2.94) were associated with higher odds of a hospitalization involving a physical restraint code. CONCLUSIONS: Physical restraint coding varied by age, sex, race, region, and disease severity. These results highlight potential disparities in physical restraint utilization, which may have consequences for equity.

Systemic histone deacetylase inhibition ameliorates the aberrant responses to acute stress in socially isolated male mice.

Adverse experiences in early life can induce maladaptive responses to acute stress in later life. Chronic social isolation during adolescence is an early life adversity that can precipitate stress-related psychiatric disorders. We found that male mice after 8 weeks of adolescent social isolation (SI) have markedly increased aggression after being exposed to 2 h of restraint stress (RS), which was accompanied by a significant increase of AMPA receptor- and NMDA receptor-mediated synaptic transmission in prefrontal cortex (PFC) pyramidal neurons of SIRS males. Compared to group-housed counterparts, SIRS males exhibited a significantly decreased level of histone H3 acetylation in PFC. Systemic administration of class I histone deacetylase inhibitors, romidepsin or MS-275, ameliorated the aggressive behaviour, as well as general social interaction deficits, of SIRS males. Electrophysiological recordings also found normalization of PFC glutamatergic currents by romidepsin treatment of SIRS male mice. These results revealed an epigenetic mechanism and intervention avenue for aggression induced by chronic social isolation. KEY POINTS: Adolescent chronic social isolation can precipitate stress-related psychiatric disorders. A significant increase of glutamatergic transmission is found in the prefrontal cortex (PFC) of socially isolated male mice exposed to an acute stress (SIRS). Treatment with class I histone deacetylase (HDAC) inhibitors ameliorates the aggressive behaviour and social interaction deficits of SIRS males, and normalizes glutamatergic currents in PFC neurons. It provides an epigenetic mechanism and intervention avenue for aberrant stress responses induced by chronic social isolation.

Residual liberty and the detained mental health patient.

Richard Griffith, Senior Lecturer in Health Law at Swansea University, considers the notion of residual liberty and the need for further authorisation when a detained patient is given treatment for a physical disorder under restraint.

The restraint chair: A qualitative study of the patient experience.

Despite initiatives to eliminate restraint from acute psychiatric care, there remain times when violent episodes threaten the safety of patients and/or staff. The restraint chair may be used in these moments and provide an alternative to four-point restraint. The purpose of this study was to examine the patient experience of the restraint chair. Patients who had an episode of restraint in the restraint chair during their hospital stay were interviewed about the experience. Participants described the experience as "unpleasant," with the majority preferring the restraint chair to other methods of restraint they had experienced. Participants indicated they could "understand" why the restraint had occurred and felt staff were "helpful" and "create safety." Finally, participants stated the hospital experience was "positive." Although the goal remains to eliminate restraint, psychiatric settings may want to consider the restraint chair as an alternative to four-point restraint for situations requiring mechanical restraint. Nurses' presence and communication with patients during the restraint process is important to the patient experience. More research is needed to verify these results.

Improving Child Passenger Safety Through Proper Restraint System Use.

Nurses could help close caregivers' knowledge gap.

Staff responses to interventions aiming to reduce mechanical restraint in adult mental health inpatient settings: a questionnaire-based survey.

PURPOSE: To explore mental health staff's responses towards interventions designed to reduce the use of mechanical restraint (MR) in adult mental health inpatient settings. METHODS: We conducted a cross-sectional, questionnaire-based survey. The questionnaire, made available online via REDCap, presented 20 interventions designed to reduce MR use. Participants were asked to rate and rank the interventions based on their viewpoints regarding the relevance and importance of each intervention. RESULTS: A total of 128 mental health staff members from general and forensic mental health inpatient units across the Mental Health Services in the Region of Southern Denmark completed the questionnaire (response rate = 21.3%). A total of 90.8% of the ratings scored either 'agree' (45.2%) or 'strongly agree' (45.6%) concerning the relevance of the interventions in reducing MR use. Overall and in the divided analysis, interventions labelled as 'building relationship' and 'patient-related knowledge' claimed high scores in the staff's rankings of the interventions' importance concerning implementation. Conversely, interventions like 'carers' and 'standardised assessments' received low scores. CONCLUSIONS: The staff generally considered that the interventions were relevant. Importance rankings were consistent across the divisions chosen, with a range of variance and dispersion being recorded among certain groups.

Psychological stress to ovalbumin peptide-specific T-cell receptor transgenic mice impairs the suppressive ability of type 1 regulatory T cell.

Numerous diseases of the immune system can be traced back to the malfunctioning of the regulatory T cells. The aetiology is unclear. Psychological stress can cause disruption to the immune regulation. The synergistic effects of psychological stress and immune response on immune regulation have yet to be fully understood. The intention of this study is to analyse the interaction between psychological stress and immune responses and how it affects the functional status of type 1 regulatory T (Tr1) cells. In this study, ovalbumin peptide T-cell receptor transgenic mice were utilised. Mice were subjected to restraint stress to induce psychological stress. An airway allergy murine model was established, in which a mouse strain with RING finger protein 20 (Rnf20)-deficient CD4+ T cells were used. The results showed that concomitant exposure to restraint stress and immune response could exacerbate endoplasmic reticulum stress in Tr1 cells. Corticosterone was responsible for the elevated expression of X-box protein-1 (XBP1) in mouse Tr1 cells after exposure to both restraint stress and immune response. XBP1 mediated the effects of corticosterone on inducing Rnf20 in Tr1 cells. The reduction of the interleukin-10 expression in Tr1 cells was facilitated by Rnf20. Inhibition of Rnf20 alleviated experimental airway allergy by restoring the immune regulatory ability of Tr1 cells. In conclusion, the functions of Tr1 cells are negatively impacted by simultaneous exposure to psychological stress and immune response. Tr1 cells' immune suppressive functions can be restored by inhibiting Rnf20, which has the translational potential for the treatment of diseases of the immune system.

Approach to acute agitation in the pediatric emergency department.

PURPOSE OF REVIEW: The complexity of pediatric mental and behavioral health (MBH) complaints presenting to emergency departments (EDs) is increasing at an alarming rate. Children may present with agitation or develop agitation during the ED visit. This causes significant distress and may lead to injury of the child, caregivers, or medical staff. This review will focus on providing safe, patient-centered care to children with acute agitation in the ED. RECENT FINDINGS: Approaching a child with acute agitation in the ED requires elucidation on the cause and potential triggers of agitation for optimal management. The first step in a patient-centered approach is to use the least restrictive means with behavioral and environmental strategies. Restraint use (pharmacologic or physical restraint) should be reserved where these modifications do not result in adequate de-escalation. The provider should proceed with medications first, using the child's medication history as a guide. The use of physical restraint is a last resort to assure the safety concerns of the child, family, or staff, with a goal of minimizing restraint time. SUMMARY: Children are increasingly presenting to EDs with acute agitation. By focusing primarily on behavioral de-escalation and medication strategies, clinicians can provide safe, patient-centered care around these events.

Prevalence and variability of restrictive care practice use (physical restraint, seclusion and chemical restraint) in adult mental health inpatient settings: A systematic review and meta-analysis.

BACKGROUND: There is a growing consensus to reduce the use of restrictive care practices in mental health settings to minimise the physical and psychological complications for patients. However, data regarding restrictive care practice use and factors contributing to variations in the proportion estimates has not previously been synthesised. AIMS: This study aimed to synthesise evidence on (1) the pooled proportions of physical restraint, seclusion or chemical restraint in adult mental health inpatients and (2) sources of variability in these proportion estimates. METHODS: Studies were identified from Scopus, MEDLINE, PsycINFO, Web of Science, Embase and CINAHL databases following the PRISMA 2020 guidelines. We conducted a meta-analysis of studies published in English language from 1 January 2010 to 15 August 2022. Binomial data were pooled using a random effect model, with 95% confidence intervals. Meta-regression was also computed to identify factors that may contribute to variations in the proportion estimates. RESULTS: A total of 77 studies were included in this meta-analysis. The pooled prevalence of physical restraint, seclusion and chemical restraint was 14.4%, 15.8% and 25.7%, respectively. Data were heterogeneous across studies (I2 > 99%). Reporting practices and geographical locations contributed to the variability in the reported estimates of restrictive care practices, with studies from Asian countries reporting higher proportions. CONCLUSION: There appear differences between geographical locations in the proportion of restrictive practices in mental health inpatients; however, this is complicated by how these prevalence data have been measured and defined. Consistency in the reporting of restrictive care practices in mental health is required to make valid comparisons between geographical regions, policy settings and practice innovations. RELEVANCE TO CLINICAL PRACTICE: Efforts are needed to develop training programmes and policy changes to ensure consistency in defining and reporting of restrictive care practices in mental health facilities. PATIENT/PUBLIC CONTRIBUTION: This is a systematic review that analysed data from previously published studies, and there was no patient/public contribution in this study. PROTOCOL REGISTRATION: The protocol for this review has been registered to PROSPERO: CRD42022335167.

Reducing Physical Restraint Use in the Medical Behavioral Unit.

OBJECTIVES: Children with behavioral health conditions often experience agitation when admitted to children's hospitals. Physical restraint should be used only as a last resort for patient agitation because it endangers the physical and psychological safety of patients and employees. At the medical behavioral unit (MBU) in our children's hospital, we aimed to decrease the weekly rate of physical restraint events per 100 MBU patient-days, independent of patient race, ethnicity, or language, from a baseline mean of 14.0 to <10 within 12 months. METHODS: Using quality improvement methodology, a multidisciplinary team designed, tested, and implemented interventions including a series of daily deescalation huddles led by a charge behavioral health clinician that facilitated individualized planning for MBU patients with the highest behavioral acuity. We tracked the weekly number of physical restraint events per 100 MBU patient-days as a primary outcome measure, weekly physical restraint event duration as a secondary outcome measure, and MBU employee injuries as a balancing measure. RESULTS: Our cohort included 527 consecutive patients hospitalized in the MBU between January 2021 and January 2023. Our 2021 baseline mean of 14.0 weekly physical restraint events per 100 MBU patient-days decreased to 10.0 during our 2022 intervention period from January through July and 4.1 in August, which was sustained through December. Weekly physical restraint event duration also decreased from 112 to 67 minutes without a change in employee injuries. CONCLUSIONS: Multidisciplinary huddles that facilitated daily deescalation planning safely reduced the frequency and duration of physical restraint events in the MBU.

Sex differences in body temperature and neural power spectra in response to repeated restraint stress.

Repeated stress is associated with an increased risk of developing psychiatric illnesses such as post-traumatic stress disorder (PTSD), which is more common in women, yet the neurobiology behind this sex difference is unknown. Habituation to repeated stress is impaired in PTSD, and recent preclinical studies have shown that female rats do not habituate as fully as male rats to repeated stress, which leads to impairments in cognition and sleep. Further research should examine sex differences after repeated stress in other relevant measures, such as body temperature and neural activity. In this study, we analyzed core body temperature and EEG power spectra in adult male and female rats during restraint, as well as during sleep transitions following stress. We found that core body temperature of male rats habituated to repeated restraint more fully than female rats. Additionally, we found that females had a higher average beta band power than males on both days of restraint, indicating higher levels of arousal. Lastly, we observed that females had lower delta band power than males during sleep transitions on Day 1 of restraint, however, females demonstrated higher delta band power than males by Day 5 of restraint. This suggests that it may take females longer to initiate sleep recovery compared with males. These findings indicate that there are differences in the physiological and neural processes of males and females after repeated stress. Understanding the way that the stress response is regulated in both sexes can provide insight into individualized treatment for stress-related disorders.

Restraint stress-induced effects on learning, memory, cognition, and expression of transcripts in different brain regions of mice.

BACKGROUND: Stress is one of the prevalent factors influencing cognition. Several studies examined the effect of mild or chronic stress on cognition. However, most of these studies are limited to a few behavioral tests or the expression of selected RNA/proteins markers in a selected brain region. METHODS: This study examined the effect of restraint stress on learning, memory, cognition, and expression of transcripts in key learning centers. Male mice were divided into three groups (n = 6/group)-control group, stress group (adult stressed group; S), and F1 group (parental stressed group). Stress group mice were subjected to physical restraint stress for 2 h before light offset for 2 weeks. The F1 group comprised adult male mice born of stressed parents. All animals were subjected to different tests and were sacrificed at the end. Transcription levels of Brain-Derived Neurotrophic Factor (Bdnf), Tyrosine kinase (TrkB), Growth Associated Protein 43 (Gap-43), Neurogranin (Ng), cAMP Response Element-Binding Protein (Creb), Glycogen synthase kinase-3ß (Gsk3ß), Interleukine-1 (IL-1) and Tumour necrosis factor-α (Tnf-α) were studied. RESULTS: Results show that both adult and parental stress negatively affect learning, memory and cognition, as reflected by taking longer time to achieve the task or showing reduced exploratory behavior. Expression of Bdnf, TrkB, Gsk3ß and Ng was downregulated, while IL-1 and Tnf-α were upregulated in the brain's cortex, thalamus, and hippocampus region of stressed mice. These effects seem to be relatively less severe in the offspring of stressed parents. CONCLUSIONS: The findings suggest that physical restraint stress can alter learning, memory, cognition, and expression of transcripts in key learning centers of brain.

Racial and Ethnic Disparities in Patient Restraint in Emergency Departments by Police Transport Status.

Importance: Black patients are more likely than White patients to be restrained during behavioral crises in emergency departments (EDs). Although the perils of policing mental health for Black individuals are recognized, it is unclear whether or to what extent police transport mediates the association between Black race and use of physical restraint in EDs. Objective: To evaluate the degree to which police transport mediates the association between Black race and use of physical restraint in EDs. Design, Setting, and Participants: This retrospective, cross-sectional study used electronic health record data from ED visits by adults (aged ≥18 years) to 3 hospitals in the southeastern US and 10 in the northeastern US between January 1, 2015, and December 31, 2022. Data were analyzed from September 1, 2022, to May 30, 2023. Exposures: Race, ethnicity, and police transport to the hospital. Main Outcomes and Measures: The primary outcome variable was the presence of an order for restraints during an ED visit. Results: A total of 4 263 437 ED visits by 1 257 339 patients (55.5% of visits by female and 44.5% by male patients; 26.1% by patients 65 years or older) were included in the study. Black patients accounted for 27.5% of visits; Hispanic patients, 17.6%; White patients, 50.3%; and other or unknown race or ethnicity, 4.6%. In models adjusted for age, sex, site, previous behavioral or psychiatric history, and visit diagnoses, Black patients were at increased odds of experiencing restraint compared with White patients (adjusted odds ratio [AOR], 1.33 [95% CI, 1.28-1.37]). Within the mediation analysis, Black patients had higher odds of being brought to the hospital by police compared with all other patients (AOR, 1.38 [95% CI, 1.34-1.42]). Patients brought to the ED under police transport had increased odds of experiencing restraint compared with all other modes of transport (AOR, 5.51 [95% CI, 5.21-5.82]). The estimated proportion of use of restraints for Black patients mediated by police transport was 10.70% (95% CI, 9.26%-12.53%). Conclusions and Relevance: In this cross-sectional study of ED visits across 13 hospitals, police transport may have mediated the association between Black race and use of physical restraint. These findings suggest a need to further explore the mechanisms by which transport to emergency care may influence disparate restrictive interventions for patients experiencing behavioral emergencies.