Relationship between plasma TNF-α levels and agitation symptoms in first episode patients with schizophrenia.

BACKGROUND: Increasing evidence suggested that immune abnormalities involved in the pathophysiology of schizophrenia. However, the relationship between immunity and clinical features has not been clarified. The aim of this study was to measure the plasma levels of tumor necrosis factor alpha (TNF-α) and soluble TNF-α receptor 1 (sTNF-α R1) and to investigate their association with agitation in first episode patients with schizophrenia (FEPS). METHODS: The plasma TNF-α and sTNF-α R1 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA) in the FEPS with (n = 36) and without agitation (n = 49) symptoms, and healthy controls (HCs, n = 54). The psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS), and the agitation symptoms were evaluated by the PANSS excitatory component (PANSS-EC). RESULTS: The plasma TNF-α levels in patients with and without agitation symptoms were significantly higher than those in HCs. The patients with agitation had significantly higher plasma TNF-α levels compared to the patients without agitation. There were no significant differences in the sTNF-α R1 levels among the three groups. Furthermore, the plasma TNF-α levels were positively correlated with the PANSS total score, Positive and General psychopathological subscores, and PANSS-EC score in the FEPS, but the relationships were not found for the plasma sTNF-α R1 levels. CONCLUSIONS: These results suggested that TNF-α might play an important role in the onset and development of agitation symptoms of schizophrenia.

Electroconvulsive therapy for the acute management of severe agitation in dementia (ECT-AD): A modified study protocol.

OBJECTIVE: This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe treatment-refractory agitation in advanced dementia. The aims are to assess agitation reduction using the Cohen-Mansfield Agitation Inventory (CMAI), evaluate tolerability and safety outcomes, and explore the long-term stability of agitation reduction and global functioning. Due to challenges encountered during implementation, including recruitment obstacles and operational difficulties, the study design was modified to an open-label format and other protocol amendments were implemented. METHODS: Initially, the RCT randomized participants 1:1 to either ECT plus usual care or simulated ECT plus usual care (S-ECT) groups. As patients were enrolled, data were collected from both ECT and simulated ECT (S-ECT) patients. The study now continues in an open-label study design where all patients receive actual ECT, reducing the targeted sample size from 200 to 50 participants. RESULTS: Study is ongoing and open to enrollment. CONCLUSION: The transition of the ECT-AD study design from an RCT to open-label design exemplifies adaptive research methodologies in response to real-world challenges. Data from both the RCT and open-label phases of the study will provide a unique perspective on the role of ECT in managing severe treatment-refractory agitation in dementia, potentially influencing future clinical practices and research approaches.

Effects of Natural Sound Therapy on Pain and Agitation Induced by Endotracheal Suctioning: A Real-World Study.

BACKGROUND: Music therapy has been used as a complementary intervention to provide synergistic analgesia for various procedures. OBJECTIVE: To evaluate the effects of natural sound therapy on pain intensity and agitation scores in intubated adult Chinese patients who received endotracheal suctioning in a critical care unit. METHODS: A prospective, real-world, randomized, double-blind, controlled study was conducted from July 2021 through February 2022 among intubated surgical intensive care unit patients in a Chinese hospital. Patients were randomly assigned to a control group receiving conventional treatment or an intervention group receiving natural sound therapy plus conventional treatment (50 patients in each group). Patients' pain intensity and agitation levels were analyzed before, during, immediately after, 5 minutes after, and 15 minutes after completion of endotracheal suctioning. Pain intensity was assessed with the Critical-Care Pain Observation Tool (CPOT); agitation was assessed with the Richmond Agitation-Sedation Scale (RASS). RESULTS: According to CPOT scores, patients in the intervention group had significant relief of pain intensity during, immediately after, and 5 minutes after endotracheal suctioning compared with patients in the control group (all P < .001). The RASS scores showed that agitation levels were significant lower in the intervention group than in the control group during (P = .002) and immediately after (P < .001) endotracheal suctioning. CONCLUSIONS: In this real-world study, natural sound therapy was part of a holistic bundle of interventions used to reduce pain and agitation in surgical intensive care unit patients during endotracheal suctioning.

Detecting agitation and aggression in persons living with dementia: a systematic review of diagnostic accuracy.

OBJECTIVE: 40-60% of persons living with dementia (PLWD) experience agitation and/or aggression symptoms. There is a need to understand the best method to detect agitation and/or aggression in PLWD. We aimed to identify agitation and/or aggression tools that are validated against a reference standard within the context of PLWD. METHODS: Our study was registered on PROSPERO (CRD42020156708). We searched MEDLINE, Embase, and PsycINFO up to April 22, 2024. There were no language or date restrictions. Studies were included if they used any tools or questionnaires for detecting either agitation or aggression compared to a reference standard among PLWD, or any studies that compared two or more agitation and/or aggression tools in the population. All screening and data extraction were done in duplicates. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Data extraction was completed in duplicates by two independent authors. We extracted demographic information, prevalence of agitation and/or aggression, and diagnostic accuracy measures. We also reported studies comparing the correlation between two or more agitation and/or aggression tools. RESULTS: 6961 articles were screened across databases. Six articles reporting diagnostic accuracy measures compared to a reference standard and 30 articles reporting correlation measurements between tools were included. The agitation domain of the Spanish NPI demonstrated the highest sensitivity (100%) against the agitation subsection of the Spanish CAMDEX. Single-study evidence was found for the diagnostic accuracy of commonly used agitation scales (BEHAVE-AD, NPI and CMAI). CONCLUSIONS: The agitation domain of the Spanish NPI, the NBRS, and the PAS demonstrated high sensitivities, and may be reasonable for clinical implementation. However, a limitation to this finding is that despite an extensive search, few studies with diagnostic accuracy measurements were identified. Ultimately, more research is needed to understand the diagnostic accuracy of agitation and/or aggression detection tools among PLWD.

Clinical Pipelines for Alzheimer's Disease Psychosis and Agitation.

Agitation and psychosis are key behavioral and psychological symptoms of Alzheimer's disease (AD). For family and caregivers of patients, such symptoms are critical factors of distress and increased burden, but medication to treat them is limited. In most cases, drugs for other neuropsychiatric diseases have been used to manage these symptoms in an off-label manner. Due to the complex pathological background of AD and limited clinical data, obtaining proof of concept for the treatment of these symptoms is challenging. However, in 2023, the U.S. Food and Drug Administration approved brexpiprazole as the first and only drug to treat agitation in AD. Several other compounds have been evaluated in clinical situations. This review highlights recent pipelines being developed for agitation and psychosis for patients living with AD.

Is there evidence for using ketamine among individuals with dementia?

The aim of this short narrative review was to evaluate the existing literature regarding the clinical use of ketamine among individuals with dementia, especially those with behavioral disturbances. PubMed, Cochrane, and Ovid (Embase, APA PsycINFO, and MEDLINE) databases were searched for abstracts using the search terms "ketamine" AND "dementia." Only articles describing the use of ketamine in individuals with dementia were included. Articles that did not include individuals with dementia, did not use ketamine, were published in a non-English language, primarily described animal studies, or were reviews were excluded. Three case reports met the inclusion criteria. One described the use of subcutaneous ketamine for depression, one described the use of intramuscular ketamine for acute agitation, and one described the use of S-ketamine as anesthesia during electroconvulsive therapy for depression and catatonia. No significant adverse effects were reported in any of the cases. Although the use of ketamine in the treatment of depression and agitation associated with dementia has potential, the current evidence remains limited. High-quality prospective studies are needed to confirm the observations of these case reports before ketamine can be used to treat behavioral disturbances in individuals with dementia.

Boarding Duration in the Emergency Department and Inpatient Delirium and Severe Agitation.

This cohort study examines the risk factors for developing delirium and/or agitation in patients in the emergency department waiting for an inpatient bed.

Unveiling the Dark Side of Datura in Pediatric Poisoning With Insights From Jordanian Experience : A Retrospective Clinical Study.

OBJECTIVES: Datura stramonium , jimsonweed, is a toxic plant with hallucinogenic properties. Although there are many studies on Datura poisoning, none reported cases in Jordan. This study offers a comprehensive review on D. stramonium ingestion, covering its epidemiology, clinical presentation, and treatment. We aimed to provide better understanding of the factors for Datura ingestion, identify prevention and management strategies, and address research challenges. METHODS: This study adopted a retrospective review design to evaluate the cases of Datura poisoning in Al Karak, province of Jordan during the spring of 2022. Data collected from medical records, toxicology databases, and consultation records were analyzed using descriptive statistics. RESULTS: The common symptoms of Datura poisoning included agitation, mydriasis, and tachycardia. The management approaches comprised supportive care, administration of Diazepam for agitation, and, in some cases, neostigmine to counteract anticholinergic effects. CONCLUSIONS: Understanding the risks associated with D. stramonium poisoning and implementing effective prevention and management strategies are crucial. This study highlights the importance of recognizing Datura poisoning as a potential diagnosis in children presenting with unexplained anticholinergic symptoms or agitation to the emergency room.

Fewer emergency department alarms is associated with reduced use of medications for acute agitation.

BACKGROUND AND OBJECTIVES: Patient monitoring systems provide critical information but often produce loud, frequent alarms that worsen patient agitation and stress. This may increase the use of physical and chemical restraints with implications for patient morbidity and autonomy. This study analyzes how augmenting alarm thresholds affects the proportion of alarm-free time and the frequency of medications administered to treat acute agitation. METHODS: Our emergency department's patient monitoring system was modified on June 28, 2022 to increase the tachycardia alarm threshold from 130 to 150 and to remove alarm sounds for several arrhythmias, including bigeminy and premature ventricular beats. A pre-post study was performed lasting 55 days before and 55 days after this intervention. The primary outcome was change in number of daily patient alarms. The secondary outcomes were alarm-free time per day and median number of antipsychotic and benzodiazepine medications administered per day. The safety outcome was the median number of patients transferred daily to the resuscitation area. We used quantile regression to compare outcomes between the pre- and post-intervention period and linear regression to correlate alarm-free time with the number of sedating medications administered. RESULTS: Between the pre- and post-intervention period, the median number of alarms per day decreased from 1332 to 845 (-37%). This was primarily driven by reduced low-priority arrhythmia alarms from 262 to 21 (-92%), while the median daily census was unchanged (33 vs 32). Median hours per day free from alarms increased from 1.0 to 2.4 (difference 1.4, 95% CI 0.8-2.1). The median number of sedating medications administered per day decreased from 14 to 10 (difference - 4, 95% CI -1 to -7) while the number of escalations in level of care to our resuscitation care area did not change significantly. Multivariable linear regression showed a 60-min increase of alarm-free time per day was associated with 0.8 (95% CI 0.1-1.4) fewer administrations of sedating medication while an additional patient on the behavioral health census was associated with 0.5 (95% CI 0.0-1.1) more administrations of sedating medication. CONCLUSION: A reasonable change in alarm parameter settings may increase the time patients and healthcare workers spend in the emergency department without alarm noise, which in this study was associated with fewer doses of sedating medications administered.

Effect of Dexmedetomidine Combined with Remifentanil on Emergence Agitation During Awakening from Sevoflurane Anesthesia for Pediatric Liver Surgery.

BACKGROUND We aimed to assess the effect of dexmedetomidine (Dex) combined with remifentanil on emergence agitation (EA) during awakening from sevoflurane anesthesia for pediatric liver surgery. MATERIAL AND METHODS Sixty children who underwent liver surgery in our hospital were prospectively selected and randomly allocated into group A (placebo+remifentanil+sevoflurane) or group B (Dex+remifentanil+sevoflurane). Mean arterial pressure (MAP) and heart rate (HR) at different time points, agitation score during awakening, behavioral status, pain level, and the incidence of postoperative adverse effects were compared in both groups. RESULTS Children in group B had lower HR and MAP levels immediately after tracheal extubation and 5 min after tracheal extubation than those in group A. The Aono's scores, PAED agitation scores, and CHIPP scores at 15 min and 30 min of admission to the PACU were lower in group B than in group A. The incidence of agitation during postoperative anesthesia awakening was lower in group B in contrast to group A. There was no significant difference in postoperative adverse reactions between group A and group B. CONCLUSIONS In pediatric liver surgery, the use of Dex+remifentanil+sevoflurane anesthesia can reduce the incidence of EA during the awakening period, stabilize hemodynamic levels, and relieve postoperative pain, and has fewer postoperative adverse effects, which warrants clinical application.

Effects of different doses of intranasal dexmedetomidine on related complications and parents' satisfaction in anesthetized children: a systematic review.

BACKGROUND: Agitation/delirium is commonly seen in children after anesthesia, and a proper dose of dexmedetomidine can prevent this complication. This study aimed to investigate the effects of different doses of Dexmedetomidine (DEX) on agitation/delirium and other complications in anesthetized children, providing clinical evidence for dose recommendations of DEX. METHODS: This study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic search was conducted in the Cochrane Library, PubMed, Web of Science, and EMBASE. Two independent researchers performed literature screening, data extraction, and assessed the methodological quality. Data analysis was conducted using R and STATA 16.0. RESULTS: In the final analysis, 20 randomized controlled trials (RCTs) involving 2521 children were included. The results showed that in comparison to normal saline, 1 µg/kg, 1.5 µg/kg, and 2 µg/kg intranasal DEX significantly reduced the incidence of post-anesthetic emergence agitation in children with the most effective dose being 2 µg/kg (SUCRA = 0.91). Compared with normal saline, 1 µg/kg, 1.5 µg/kg, and 2 µg/kg intranasal DEX reduced patient's need for postoperative analgesia, with the most effective dose being 1.5 µg/kg (SUCRA = 0.78). However, 1 µg/kg DEX performed the best in reducing Pediatric Anaesthesia Emergence Delirium (PAED) Scale score (SUCRA = 0.88). CONCLUSION: Compared with normal saline, intranasal administration of 2 µg/kg DEX and 1.5 µg/kg DEX are the optimal doses to reduce the incidence of agitation and the need for postoperative pain relief in children under general anesthesia. Given effectiveness and safety, intranasal use of 1 µg/kg DEX appears to be the most effective dosage for anesthetized children.

Replacing the Clinical Institute Withdrawal Assessment-Alcohol revised with the modified Richmond Agitation and Sedation Scale for alcohol withdrawal to support management of alcohol withdrawal symptoms: potential impact on length of stay and complications.

PURPOSE: We evaluated impact on length of stay and possible complications of replacing the Clinical Institute Withdrawal Assessment-Alcohol Revised (CIWA-Ar) scale with a slightly modified Richmond Agitation and Sedation Scale (mRASS-AW) to support managing patients admitted with alcohol withdrawal symptoms in a community hospital. Since mRASS-AW is viewed as easier and quicker to use than CIWA-Ar, provided use of mRASS-AW does not worsen outcomes, it could be a safe alternative in a busy ED environment and offer an opportunity to release nursing time to care. METHODS: Retrospective time-series analysis of mean quarterly length of stay. All analyses exclusively used our hospital's administrative discharge diagnoses database. During April 1st 2012 to December 14th 2014, the CIWA-Ar was used in the ED and in-patient units to guide benzodiazepine dosing decisions for alcohol withdrawal symptoms. After this point, CIWA-Ar was replaced with mRASS-AW. Data was evaluated until December 31st 2020. PRIMARY OUTCOME: mean quarterly length of stay. SECONDARY OUTCOMES: delirium, intensive care unit (ICU) admission, other post-admission complications, mortality. RESULTS: N = 1073 patients. No association between length of stay and scale switch (slope change 0.3 (95% CI - 0.03 to 0.6), intercept change, 0.06 (- 0.03 to 0.2). CIWA-Ar (n = 317) mean quarterly length of stay, 5.7 days (95% 4.2-7.1), mRASS-AW (n = 756) 5.0 days (95% CI 4.3-5.6). Incidence of delirium, ICU admission or mortality was not different. However, incidence of other post-admission complications was higher with CIWA-Ar (6.6%) than mRASS-AW (3.4%) (p = 0.020). CONCLUSIONS: This was the first study to compare patient outcomes associated with using mRASS-AW for alcohol withdrawal symptoms outside the ICU. Replacing CIWA-Ar with mRASS-AW did not worsen length of stay or complications. These findings provide some evidence that mRASS-AW could be considered an alternative to CIWA-Ar and potentially may provide an opportunity to release nursing time to care.

ABSTRAIT: BUT: Nous avons évalué l'impact sur la durée du séjour et les complications possibles du remplacement de l'échelle Clinical Institute Withdrawal Assessment- Alcohol Revised (CIWA-Ar) par une échelle d'agitation et de sédation de Richmond légèrement modifiée (mRASS-AW) soutenir la prise en charge des patients admis avec des symptômes de sevrage d'alcool dans un hôpital communautaire. Étant donné que le mRASS-AW est considéré comme plus facile et plus rapide à utiliser que le CIWA-Ar, à condition que l'utilisation du mRASS-AW n'aggrave pas les résultats, il pourrait s'agir d'une solution de rechange sécuritaire dans un environnement de SU occupé et offrir une occasion de libérer du temps pour les soins infirmiers. MéTHODES: Analyse rétrospective de séries chronologiques de la durée moyenne trimestrielle du séjour. Toutes les analyses utilisaient exclusivement la base de données des diagnostics de sortie administrative de notre hôpital. Entre le 1er avril 2012 et le 14 décembre 2014, le CIWA-Ar a été utilisé dans les unités de soins intensifs et de soins aux patients hospitalisés pour guider les décisions de dosage des benzodiazépines pour les symptômes de sevrage de l'alcool. Après ce point, CIWA-Ar a été remplacé par mRASS-AW. Les données ont été évaluées jusqu'au 31 décembre 2020. Résultat principal : durée moyenne trimestrielle du séjour. Résultats secondaires : délire, admission en unité de soins intensifs (USI), autres complications post-admission, mortalité. RéSULTATS: N = 1073 patients. Aucune association entre la durée de séjour et le changement d'échelle (changement de pente 0,3 (IC à 95 % -0,03 à 0,6), changement d'interception, 0,06 (-0,03 à 0,2). CIWA-Ar (n = 317) durée moyenne trimestrielle du séjour, 5,7 jours (95 % 4,2 à 7,1), mRASS-AW (n = 756) 5,0 jours (95 % IC 4,3 à 5,6). L'incidence du délire, de l'admission aux soins intensifs ou de la mortalité n'était pas différente. Cependant, l'incidence d'autres complications post-admission était plus élevée avec CIWA-Ar (6,6%) que mRASS-AW (3,4%) (p = 0,020). CONCLUSIONS: Il s'agissait de la première étude à comparer les résultats des patients associés à l'utilisation du mRASS-AW pour les symptômes de sevrage alcoolique en dehors des soins intensifs. Le remplacement de CIWA-Ar par mRASS-AW n'a pas aggravé la durée du séjour ou les complications. Ces résultats fournissent certaines preuves que le mRASS-AW pourrait être considéré comme une alternative au CIWA-Ar et pourrait potentiellement fournir une occasion de libérer du temps de soins infirmiers.

Use of actigraphy for monitoring agitation and rest-activity cycles in patients with acute traumatic brain injury in the ICU.

BACKGROUND: In traumatic brain injury patients (TBI) admitted to the intensive care unit (ICU), agitation can lead to accidental removal of catheters, devices as well as self-extubation and falls. Actigraphy could be a potential tool to continuously monitor agitation. The objectives of this study were to assess the feasibility of monitoring agitation with actigraphs and to compare activity levels in agitated and non-agitated critically ill TBI patients. METHODS: Actigraphs were placed on patients' wrists; 24-hour monitoring was continued until ICU discharge or limitation of therapeutic efforts. Feasibility was assessed by actigraphy recording duration and missing activity count per day. RESULTS: Data from 25 patients were analyzed. The mean number of completed day of actigraphy per patient was 6.5 ± 5.1. The mean missing activity count was 20.3 minutes (±81.7) per day. The mean level of activity measured by raw actigraphy counts per minute over 24 hours was higher in participants with agitation than without agitation. CONCLUSIONS: This study supports the feasibility of actigraphy use in TBI patients in the ICU. In the acute phase of TBI, agitated patients have higher levels of activity, confirming the potential of actigraphy to monitor agitation.

Assessment and report of individual symptoms in studies of delirium in postoperative populations: a systematic review.

OBJECTIVES: Delirium is most often reported as present or absent. Patients with symptoms falling short of the diagnostic criteria for delirium fall into 'no delirium' or 'control' groups. This binary classification neglects individual symptoms and may be hindering identification of the pathophysiology underlying delirium. This systematic review investigates which individual symptoms of delirium are reported by studies of postoperative delirium in adults. METHODS: Medline, EMBASE and Web of Science databases were searched on 03 June 2021 and 06 April 2023. Two reviewers independently examined titles and abstracts. Each paper was screened in duplicate and conflicting decisions settled by consensus discussion. Data were extracted, qualitatively synthesised and narratively reported. All included studies were quality assessed. RESULTS: These searches yielded 4,367 results. After title and abstract screening, 694 full-text studies were reviewed, and 62 deemed eligible for inclusion. This review details 11,377 patients including 2,049 patients with delirium. In total, 78 differently described delirium symptoms were reported. The most reported symptoms were inattention (N = 29), disorientation (N = 27), psychomotor agitation/retardation (N = 22), hallucination (N = 22) and memory impairment (N = 18). Notably, psychomotor agitation and hallucinations are not listed in the current Diagnostic and Statistical Manual for Mental Disorders-5-Text Revision delirium definition. CONCLUSIONS: The 78 symptoms reported in this systematic review cover domains of attention, awareness, disorientation and other cognitive changes. There is a lack of standardisation of terms, and many recorded symptoms are synonyms of each other. This systematic review provides a library of individual delirium symptoms, which may be used to inform future reporting.

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.

Fixed dose ketamine for prehospital management of hyperactive delirium with severe agitation.

INTRODUCTION: Patients exhibiting signs of hyperactive delirium with severe agitation (HDSA) may require sedating medications for stabilization and safe transport to the hospital. Determining the patient's weight and calculating the correct weight-based dose may be challenging in an emergency. A fixed dose ketamine protocol is an alternative to the traditional weight-based administration, which may also reduce dosing errors. The objective of this study was to evaluate the frequency and characteristics of adverse events following pre-hospital ketamine administration for HDSA. METHODS: Emergency Medical Services (EMS) records from four agencies were searched for prehospital ketamine administration. Cases were included if a 250 mg dose of ketamine was administered on standing order to an adult patient for clinical signs consistent with HDSA. Protocols allowed for a second 250 mg dose of ketamine if the first dose was not effective. Both the 250 mg initial dose and the total prehospital dose were analyzed for weight based dosing and adverse events. RESULTS: Review of 132 cases revealed 60 cases that met inclusion criteria. Patients' median weight was 80 kg (range: 50-176 kg). No patients were intubated by EMS, one only requiring suction, three required respiratory support via bag valve mask (BVM). Six (10%) patients were intubated in the emergency department (ED) including the three (5%) supported by EMS via BVM, three (5%) others who were sedated further in the ED prior to requiring intubation. All six patients who were intubated were discharged from the hospital with a Cerebral Performance Category (CPC) 1 score. The weight-based dosing equivalent for the 250 mg initial dose (OR: 2.62, CI: 0.67-10.22) and the total prehospital dose, inclusive of the 12 patients that were administered a second dose, (OR: 0.74, CI: 0.27, 2.03), were not associated with the need for intubation. CONCLUSION: The 250 mg fixed dose of ketamine was not >5 mg/kg weight-based dose equivalent for all patients in this study. Although a second 250 mg dose of ketamine was permitted under standing orders, only 12 (20%) of the patients were administered a second dose, none experienced an adverse event. This indicates that the 250 mg initial dose was effective for 80% of the patients. Four patients with prehospital adverse events likely related to the administration of ketamine were found. One required suction, three (5%) requiring BVM respiratory support by EMS were subsequently intubated upon arrival in the ED. All 60 patients were discharged from the hospital alive. Further research is needed to determine an optimal single administration dose for ketamine in patients exhibiting signs of HDSA, if employing a standardized fixed dose medication protocol streamlines administration, and if the fixed dose medication reduces the occurrence of dosage errors.

MiR-21 Regulates Growth and Migration of Cervical Cancer Cells by RECK Signaling Pathway.

Expression of miR-21 has been found to be altered in almost all types of cancers, and it has been classified as an oncogenic microRNA. In addition, the expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study, we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells, there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3'-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed, and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.

Effects of cariprazine on reducing symptoms of irritability, hostility, and agitation in patients with manic or mixed episodes of bipolar I disorder.

BACKGROUND: Hostility, irritability, and agitation are common in patients with bipolar I disorder. Post hoc analyses evaluated the effect of cariprazine on these symptoms in patients with bipolar I mania. METHODS: Data were pooled from three randomized, double-blind, placebo-controlled phase 3 cariprazine trials in adults with bipolar I manic/mixed episodes (NCT00488618, NCT01058096, NCT01058668); pooled cariprazine doses (3-12 mg/d) were analyzed. Patients were categorized into hostility/irritability and agitation subgroups by baseline scores: Young Mania Rating Scale (YMRS) irritability and disruptive-aggressive behavior items score ≥ 2; Positive and Negative Syndrome Scale (PANSS) hostility item ≥ 2; PANSS-Excited Component (PANSS-EC) total score ≥ 14 and score ≥ 4 on ≥ 1 individual item. Changes from baseline to week 3 in hostility/irritability- and agitation-related outcomes were evaluated. Adjustments were made for the presence of other manic symptoms, sedation, and akathisia. RESULTS: Most patients met subgroup inclusion criteria (YMRS hostility = 930; PANSS hostility = 841, PANSS-EC agitation = 486). In the YMRS subgroup, least squares mean differences in change from baseline were statistically significant for cariprazine versus placebo on YMRS hostility/irritability-related items (irritability [-0.93], disruptive-aggressive behavior [-0.79], combined [-1.75]; P ≤ 0.001 each), YMRS total score (-5.92, P ≤ 0.0001), and all individual YMRS items (-0.25 to -0.93, P ≤ 0.0001); differences remained significant after adjustment for other manic symptoms, sedation, and akathisia. Differences in PANSS hostility and PANSS-EC subgroups were significant for cariprazine versus placebo (P ≤ 0.001). LIMITATIONS: Post hoc analysis. CONCLUSION: Cariprazine demonstrated specific antihostility/irritability and anti-agitation effects in patients with manic/mixed episodes of bipolar I disorder and baseline hostility, irritability, or agitation.