Time-dependent effect of antipsychotic discontinuation and dose reduction on social functioning and subjective quality of life-a multilevel meta-analysis.

Background: Meta-analyses indicate superiority of antipsychotic maintenance treatment over discontinuation within up to 24 months after treatment initiation for patients with schizophrenia-spectrum disorders. In terms of functional recovery, long-term trials show improved functioning after discontinuation, suggesting a time-dependent effect of antipsychotic maintenance. However, these trials were not included in previous meta-analyses. We therefore investigated whether the effect of antipsychotic maintenance treatment vs. discontinuation on social functioning and quality of life varies by trial length. Methods: The study was preregistered with PROSPERO (CRD42021248933). PubMed, PsycINFO, Web of Science, Embase and trial registers were systematically searched on 8th November 2021 and updated on 25th June, 2023 and 10th August, 2023 for studies that compared antipsychotic maintenance to discontinuation and reported data on social functioning or subjective quality of life in patients with schizophrenia-spectrum disorders. Risk of bias was assessed with the RoB 2, the ROBINS-I and the RoB-ME tools. Quality of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Findings: We included k = 35 studies (N = 5924) with follow-ups between one month and 15 years. Overall, maintenance and discontinuation did not differ on social functioning (k = 32; n = 5330; SMD = 0.204; p = 0.65; 95% CI [-0.69, 1.10]) or quality of life (k = 10; n = 943; SMD = -0.004; p = 0.97; 95% CI [-0.22, 0.21]), whilst subgroup analyses of middle- (2-5 years; k = 7; n = 1032; SMD = 0.68; 95% CI [0.06, 1.28]) and long-term follow-ups (>5 years; k = 2; n = 356; SMD = 1.04; 95% CI [0.82, 1.27]) significantly favoured discontinuation. However, the quality of evidence was rated as very low. Interpretation: Although our findings suggest a time-dependent decrease in the effect of maintenance treatment on social functioning, interpretation of these findings is limited by the serious risk of bias in middle- and long-term trials. Therefore, any conclusions regarding the long-term benefits of antipsychotic treatment or discontinuation for functional recovery are premature and more high-quality trials tailored to comparing state of the art maintenance treatment vs. discontinuation are needed. Funding: None.

Reasons police respond in schools: An analysis of narrative data from police incident reports.

BACKGROUND: Communities across the U.S. have acted to eliminate or curb police presence in schools. These efforts have primarily focused on School Resource Officers. However, school staff also call upon local police to respond in their buildings, for example by calling 911. The reasons that police are called upon to respond in schools has rarely been studied. OBJECTIVE: The current study aimed to identify the primary reasons that local police were asked to respond to incidents in one urban school district, and the outcomes of those responses. PARTICIPANTS AND SETTING: We analyzed 882 police incident report narratives, selected from a stratified sample of 57 schools in one urban school district during the 2017-18 school year. Incident reports, which were written by officers responding in schools, included narrative descriptions of officer intervention, the events precipitating police involvement, and outcomes of incidents. METHODS: By coding incident report narratives, we identified categories describing the reasons for police response to events in schools and the outcomes of those events. RESULTS: Most incident reports originating from school addresses (n = 730; 82.8 %) involved students. Among those reports, police most frequently responded to instances of sexual physical violence (17.5 %), physical assault (15.8 %), dysregulated behavior (11.2 %), threatening language (10.8 %), and threat of or actual school violence (4.4 %). Incidents involving students most often resulted in: (1) parents/guardians being contacted (57.3 %), (2) schools engaging in disciplinary actions (39.7 %) or school safety actions (27.0 %), and (3) child maltreatment reports being made to Crimes Against Children (a subdivision of the police department focused on child maltreatment; 26.0 %) or to the Department of Children and Families (26.2 %). CONCLUSIONS: Findings indicate that many events leading to police responses in schools are related to maltreatment and behavioral health. These events rarely result in a criminal justice response, and most often result in action by families and schools (e.g., contacting parents/guardians, school disciplinary/safety actions), and filed reports of maltreatment. Additional supports in these areas may have the potential to reduce the perceived need to call upon police and to provide more direct access to services for students.

Correlation between Clinical Characteristics and Antibody Levels in COVID-19 Convalescent Plasma Donor Candidates.

COVID-19 convalescent plasma (CCP) with high neutralizing antibodies has been suggested in preventing disease progression in COVID-19. In this study, we investigated the relationship between clinical donor characteristics and neutralizing anti-SARS-CoV-2 antibodies in CCP donors. COVID-19 convalescent plasma donors were included into the study. Clinical parameters were recorded and anti-SARS-CoV-2 antibody levels (Spike Trimer, Receptor Binding Domain (RBD), S1, S2 and nucleocapsid protein) as well as ACE2 binding inhibition were measured. An ACE2 binding inhibition < 20% was defined as an inadequate neutralization capacity. Univariate and multivariable logistic regression analysis was used to detect the predictors of inadequate neutralization capacity. Ninety-one CCP donors (56 female; 61%) were analyzed. A robust correlation between all SARS-CoV-2 IgG antibodies and ACE2 binding inhibition, as well as a positive correlation between donor age, body mass index, and a negative correlation between time since symptom onset and antibody levels were found. We identified time since symptom onset, normal body mass index (BMI), and the absence of high fever as independent predictors of inadequate neutralization capacity. Gender, duration of symptoms, and number of symptoms were not associated with SARS-CoV-2 IgG antibody levels or neutralization. Neutralizing capacity was correlated with SARS-CoV-2 IgG antibodies and associated with time since symptom onset, BMI, and fever. These clinical parameters can be easily incorporated into the preselection of CCP donors.

SARS-CoV-2 vaccination of convalescents boosts neutralization capacity against Omicron subvariants BA.1, BA.2 and BA.5 and can be predicted by anti-S antibody concentrations in serological assays.

Background: Recent data on immune evasion of new SARS-CoV-2 variants raise concerns about the efficacy of antibody-based COVID-19 therapies. Therefore, in this study the in-vitro neutralization capacity against SARS-CoV-2 variant B.1 and the Omicron subvariants BA.1, BA.2 and BA.5 of sera from convalescent individuals with and without boost by vaccination was assessed. Methods and findings: The study included 313 serum samples from 155 individuals with a history of SARS-CoV-2 infection, divided into subgroups without (n=25) and with SARS-CoV-2 vaccination (n=130). We measured anti-SARS-CoV-2 antibody concentrations by serological assays (anti-SARS-CoV-2-QuantiVac-ELISA (IgG) and Elecsys Anti-SARS-CoV-2 S) and neutralizing titers against B.1, BA.1, BA.2 and BA.5 in a pseudovirus neutralization assay. Sera of the majority of unvaccinated convalescents did not effectively neutralize Omicron sublineages BA.1, BA.2 and BA.5 (51.7%, 24.1% and 51.7%, resp.). In contrast, 99.3% of the sera of superimmunized individuals (vaccinated convalescents) neutralized the Omicron subvariants BA.1 and BA.5 and 99.6% neutralized BA.2. Neutralizing titers against B.1, BA.1, BA.2 and BA.5 were significantly higher in vaccinated compared to unvaccinated convalescents (p<0.0001) with 52.7-, 210.7-, 141.3- and 105.4-fold higher geometric mean of 50% neutralizing titers (NT50) in vaccinated compared to unvaccinated convalescents. 91.4% of the superimmunized individuals showed neutralization of BA.1, 97.2% of BA.2 and 91.5% of BA.5 with a titer ≥ 640. The increase in neutralizing titers was already achieved by one vaccination dose. Neutralizing titers were highest in the first 3 months after the last immunization event. Concentrations of anti-S antibodies in the anti-SARS-CoV-2-QuantiVac-ELISA (IgG) and Elecsys Anti-SARS-CoV-2 S assays predicted neutralization capacity against B.1 and Omicron subvariants BA.1, BA.2 and BA.5. Conclusions: These findings confirm substantial immune evasion of the Omicron sublineages, which can be overcome by vaccination of convalescents. This informs strategies for choosing of plasma donors in COVID-19 convalescent plasma programs that shall select specifically vaccinated convalescents with very high titers of anti-S antibodies.

Calls from Boston Schools for Police Psychiatric Emergency Response: A Study of 911 Call Record Data from 2014 to 2018.

This study examines patterns and trends in 911 calls from Boston public school addresses related to mental health and physical assaults/fights generated from 2014 to 2018. We analyzed 12,113 Boston Police Department (BPD) 911 call records from 102 Boston Public School addresses during the 2014-2018 school years. In addition, we separately analyzed calls coded by BPD as Emotionally Disturbed Person ("EDP"), indicating a psychiatric crisis was the primary reason for the call, as well as calls coded as "Fight," "Assault," or "Assault and battery." Call frequency ranged from 0 to 277 per school each year. Although the annual average number of calls increased each school year over the 4-year period, this was primarily due to an increase in hang-ups and abandoned calls. Overall, 7.4% calls were coded as EDP and 6.5% were coded as assault/fight. Call volume was highest in the middle of the school day, with a median time of 12 pm. EDP calls were significantly earlier in the day than non-EDP calls, and the percentage of calls labeled as EDP decreased in frequency each day over the course of the week. There were more overall 911 calls, on average, per day in late spring than in other seasons. The frequency with which schools call upon police as emergency service providers for psychiatric crises indicates a need for additional school-based resources. Such resources may be most effective if they are allocated mid-day, responsive to changing student needs over the course of the week, and increased in spring.

One-year follow-up of the CAPSID randomized trial for high-dose convalescent plasma in severe COVID-19 patients.

BACKGROUNDResults of many randomized trials on COVID-19 convalescent plasma (CCP) have been reported, but information on long-term outcome after CCP treatment is limited. The objectives of this extended observation of the randomized CAPSID trial are to assess long-term outcome and disease burden in patients initially treated with or without CCP.METHODSOf 105 randomized patients, 50 participated in the extended observation. Quality of life (QoL) was assessed by questionnaires and a structured interview. CCP donors (n = 113) with asymptomatic to moderate COVID-19 were included as a reference group.RESULTSThe median follow-up of patients was 396 days, and the estimated 1-year survival was 78.7% in the CCP group and 60.2% in the control (P = 0.08). The subgroup treated with a higher cumulative amount of neutralizing antibodies showed a better 1-year survival compared with the control group (91.5% versus 60.2%, P = 0.01). Medical events and QoL assessments showed a consistent trend for better results in the CCP group without reaching statistical significance. There was no difference in the increase in neutralizing antibodies after vaccination between the CCP and control groups.CONCLUSIONThe trial demonstrated a trend toward better outcome in the CCP group without reaching statistical significance. A predefined subgroup analysis showed a significantly better outcome (long-term survival, time to discharge from ICU, and time to hospital discharge) among those who received a higher amount of neutralizing antibodies compared with the control group. A substantial long-term disease burden remains after severe COVID-19.Trial registrationEudraCT 2020-001310-38 and ClinicalTrials.gov NCT04433910.FundingBundesministerium für Gesundheit (German Federal Ministry of Health).

Increased plasma level of soluble P-selectin in non-hospitalized COVID-19 convalescent donors.

BACKGROUND: The coronavirus disease-2019 (COVID-19) is a systemic disease with severe implications on the vascular and coagulation system. A procoagulant platelet phenotype has been reported at least in the acute disease phase. Soluble P-selectin (sP-sel) in the plasma is a surrogate biomarker of platelet activation. Increased plasma levels of sP-sel have been reported in hospitalized COVID-19 patients associated with disease severity. Here, we evaluated in a longitudinal study the sP-sel plasma concentration in blood donors who previously suffered from moderate COVID-19. METHODS: 154 COVID-19 convalescent and 111 non-infected control donors were recruited for plasma donation and for participation in the CORE research trial. First donation (T1) was performed 43-378 days after COVID-19 diagnosis. From most of the donors the second (T2) plasma donation including blood sampling was obtained after a time period of 21-74 days and the third (T3) donation after additional 22-78 days. Baseline characteristics including COVID-19 symptoms of the donors were recorded based on a questionnaire. Platelet function was measured at T1 by flow cytometry and light transmission aggregometry in a representative subgroup of 25 COVID-19 convalescent and 28 control donors. The sP-sel plasma concentration was determined in a total of 704 samples by using a commercial ELISA. RESULTS: In vitro platelet function was comparable in COVID-19 convalescent and control donors at T1. Plasma samples from COVID-19 convalescent donors revealed a significantly higher sP-sel level compared to controls at T1 (1.05 ± 0.42 ng/mL vs. 0.81 ± 0.30 ng/mL; p < 0.0001) and T2 (0.96 ± 0.39 ng/mL vs. 0.83 ± 0.38 ng/mL; p = 0.0098). At T3 the sP-sel plasma level was comparable in both study groups. Most of the COVID-19 convalescent donors showed a continuous decrease of sP-sel from T1 to T3. CONCLUSION: Increased sP-sel plasma concentration as a marker for platelet or endothelial activation could be demonstrated even weeks after moderate COVID-19, whereas, in vitro platelet function was comparable with non-infected controls. We conclude that COVID-19 and additional individual factors could lead to an increase of the sP-sel plasma level.

Donors for SARS-CoV-2 Convalescent Plasma for a Controlled Clinical Trial: Donor Characteristics, Content and Time Course of SARS-CoV-2 Neutralizing Antibodies.

BACKGROUND: Convalescent plasma is one of the treatment options for COVID-19 which is currently being investigated in many clinical trials. Understanding of donor and product characteristics is important for optimization of convalescent plasma. METHODS: Patients who had recovered from CO-VID-19 were recruited as donors for COVID-19 convalescent plasma (CCP) for a randomized clinical trial of CCP for treatment of severe COVID-19 (CAPSID Trial). Titers of neutralizing antibodies were measured by a plaque-reduction neutralization test (PRNT). Correlation of antibody titers with host factors and evolution of neutralizing antibody titers over time in repeat donors were analysed. RESULTS: A series of 144 donors (41% females, 59% males; median age 40 years) underwent 319 plasmapheresis procedures providing a median collection volume of 850 mL and a mean number of 2.7 therapeutic units per plasmapheresis. The majority of donors had a mild or moderate course of COVID-19. The titers of neutralizing antibodies varied greatly between CCP donors (from <1:20 to >1:640). Donor factors (gender, age, ABO type, body weight) did not correlate significantly with the titer of neutralizing antibodies. We observed a significant positive correlation of neutralization titers with the number of reported COVID-19 symptoms and with the time from SARS-CoV-2 diagnosis to plasmapheresis. Neutralizing antibody levels were stable or increased over time in 58% of repeat CCP donors. Mean titers of neutralizing antibodies of first donation and last donation of repeat CCP donors did not differ significantly (1:86 at first compared to 1:87 at the last donation). There was a significant correlation of neutralizing antibodies measured by PRNT and anti-SARS-CoV-2 IgG and IgA antibodies which were measured by ELISA. CCP donations with an anti-SARS-CoV-2 IgG antibody content above the 25th percentile were substantially enriched for CCP donations with higher neutralizing antibody levels. CONCLUSION: We demonstrate the feasibility of collection of a large number of CCP products under a harmonized protocol for a randomized clinical trial. Titers of neutralizing antibodies were stable or increased over time in a subgroup of repeat donors. A history of higher number of COVID-19 symptoms and higher levels of anti-SARS-CoV-2 IgG and IgA antibodies in immunoassays can preselect donations with higher neutralizing capacity.

Police and mental health in elementary and secondary schools: A systematic review of the literature and implications for nursing.

WHAT IS KNOWN ON THIS SUBJECT?: Police are often called on to respond to student mental health needs in schools. School nurses, who are part of interdisciplinary mental health teams, may collaborate with responding police officers. Currently, there are no reviews of the literature describing the use of police to respond to mental health crises in schools. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This systematic review found six articles addressing police response to student mental health needs in elementary and secondary schools. Articles primarily focused on the School Resource Officer programme; however, there was a lack of research on the effectiveness of this and other programmes in addressing the mental health needs of students. This paper highlights a significant gap in knowledge about how police are involved in responding to student mental health crises within schools. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Understanding how police respond to mental health crises on school campuses will help nurses serve in collaborative roles with responding officers. This study highlights gaps in research that need to be addressed for researchers and policymakers to best support students in crisis. ABSTRACT: INTRODUCTION: Response to student mental health crises involves interdisciplinary school-community teams, which can include police officers. This paper presents the first systematic review of literature on how police address mental health in school settings. Results have implications for school nurses interacting with responding police. QUESTION/AIM: How are police involved in responding to student mental health needs in elementary and secondary schools? METHOD: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, six articles met criteria for inclusion in this review. RESULTS: Two themes were identified: (1) descriptions of roles of police in schools and (2) studies presenting programmes or models of police engagement. The most common use of police in schools is through the School Resource Officer model. DISCUSSION: There are very few studies examining police involvement in mental health response in schools and little data available on whether prevailing models are effective. We are therefore unable to ascertain what impact school police have in responding to mental health crises or the extent to which they interact with school nurses. IMPLICATIONS FOR PRACTICE: Understanding mental health crisis responses in schools can inform policy, practice, research and education for police and school providers, including nurses.

Nursing Group Empowerment: Instrument Revision.

BACKGROUND AND PURPOSE: The Sieloff-King Assessment of Group Empowerment with Organizations (SKAGEO) has demonstrated consistent reliability and validity, although past participants reported the need for revisions to further improve its clarity and ease of use in research. The purpose of this research was to use focus groups to revise the SKAGEO. METHODS: Two focus groups were held (seven RNs and one student nurse). Thematic analysis was used to analyze the focus group discussions. RESULTS: Five major themes, and eleven subthemes, were identified as areas for future revisions to further improve the instrument's clarity and use in research. CONCLUSIONS: Revisions in the SKAGEO, based on the areas identified by the focus groups, would result in an instrument that would more easily be understood and incorporated into research.

Moderate exercise promotes human RBC-NOS activity, NO production and deformability through Akt kinase pathway.

BACKGROUND: Nitric oxide (NO) produced by nitric oxide synthase (NOS) in human red blood cells (RBCs) was shown to depend on shear stress and to exhibit important biological functions, such as inhibition of platelet activation. In the present study we hypothesized that exercise-induced shear stress stimulates RBC-NOS activation pathways, NO signaling, and deformability of human RBCs. METHODS/FINDINGS: Fifteen male subjects conducted an exercise test with venous blood sampling before and after running on a treadmill for 1 hour. Immunohistochemical staining as well as western blot analysis were used to determine phosphorylation and thus activation of Akt kinase and RBC-NOS as well as accumulation of cyclic guanylyl monophosphate (cGMP) induced by the intervention. The data revealed that activation of NO upstream located enzyme Akt kinase was significantly increased after the test. Phosphorylation of RBC-NOSSer(1177) was also significantly increased after exercise, indicating activation of RBC-NOS through Akt kinase. Total detectable RBC-NOS content and phosphorylation of RBC-NOSThr(495) were not affected by the intervention. NO production by RBCs, determined by DAF fluorometry, and RBC deformability, measured via laser-assisted-optical-rotational red cell analyzer, were also significantly increased after the exercise test. The content of the NO downstream signaling molecule cGMP increased after the test. Pharmacological inhibition of phosphatidylinositol 3 (PI3)-kinase/Akt kinase pathway led to a decrease in RBC-NOS activation, NO production and RBC deformability. CONCLUSION/SIGNIFICANCE: This human in vivo study first-time provides strong evidence that exercise-induced shear stress stimuli activate RBC-NOS via the PI3-kinase/Akt kinase pathway. Actively RBC-NOS-produced NO in human RBCs is critical to maintain RBC deformability. Our data gain insights into human RBC-NOS regulation by exercise and, therefore, will stimulate new therapeutic exercise-based approaches for patients with microvascular disorders.

The histidine kinase-related domain of Arabidopsis phytochrome a controls the spectral sensitivity and the subcellular distribution of the photoreceptor.

Phytochrome A (phyA) is the primary photoreceptor for sensing extremely low amounts of light and for mediating various far-red light-induced responses in higher plants. Translocation from the cytosol to the nucleus is an essential step in phyA signal transduction. EID1 (for EMPFINDLICHER IM DUNKELROTEN LICHT1) is an F-box protein that functions as a negative regulator in far-red light signaling downstream of the phyA in Arabidopsis (Arabidopsis thaliana). To identify factors involved in EID1-dependent light signal transduction, pools of ethylmethylsulfonate-treated eid1-3 seeds were screened for seedlings that suppress the hypersensitive phenotype of the mutant. The phenotype of the suppressor mutant presented here is caused by a missense mutation in the PHYA gene that leads to an amino acid transition in its histidine kinase-related domain. The novel phyA-402 allele alters the spectral sensitivity and the persistence of far-red light-induced high-irradiance responses. The strong eid1-3 suppressor phenotype of phyA-402 contrasts with the moderate phenotype observed when phyA-402 is introgressed into the wild-type background, which indicates that the mutation mainly alters functions in an EID1-dependent signaling cascade. The mutation specifically inhibits nuclear accumulation of the photoreceptor molecule upon red light irradiation, even though it still interacts with FHY1 (for far-red long hypocotyl 1) and FHL (for FHY1-like protein), two factors that are essential for nuclear accumulation of phyA. Degradation of the mutated phyA is unaltered even under light conditions that inhibit its nuclear accumulation, indicating that phyA degradation may occur mostly in the cytoplasm.

Molecular and functional characterization of Arabidopsis Cullin 3A.

Cullin proteins, which belong to multigenic families in all eukaryotes, associate with other proteins to form ubiquitin protein ligases (E3s) that target substrates for proteolysis by the 26S proteasome. Here, we present the molecular and genetic characterization of a plant Cullin3. In contrast to fungi and animals, the genome of the model plant Arabidopsis thaliana contains two related CUL3 genes, called CUL3A and CUL3B. We found that CUL3A is ubiquitously expressed in plants and is able to interact with the ring-finger protein RBX1. A genomic search revealed the existence of at least 76 BTB-domain proteins in Arabidopsis belonging to 11 major families. Yeast two-hybrid experiments indicate that representative members of certain families are able to physically interact with both CUL3A and CUL3B, suggesting that Arabidopsis CUL3 forms E3 protein complexes with certain BTB domain proteins. In order to determine the function of CUL3A, we used a reverse genetic approach. The cul3a null mutant flowers slightly later than the control plants. Furthermore, this mutant exhibits a reduced sensitivity of the inhibition of hypocotyl growth in far-red light and miss-expresses COP1. The viability of the mutant plants suggests functional redundancy between the two CUL3 genes in Arabidopsis.