Mapping respiratory syncytial virus fusion protein interactions with the receptor IGF1R and the impact of alanine-scanning mutagenesis on viral infection.

Respiratory syncytial virus (RSV) has two main surface glycoproteins, the attachment glycoprotein (G) and the fusion (F) protein, which together mediate viral entry. Attachment is mediated by the RSV-G protein, while the RSV-F protein makes specific contact with the cellular insulin-like growth factor 1 receptor (IGF1R). This interaction leads to IGF1R activation and initiates a signalling cascade that calls the co-receptor, nucleolin, from the nucleus to the cell surface, where it can trigger viral fusion. We performed molecular docking analysis, which provided a potential set of 35 residues in IGF1R that may be important for interactions with RSV-F. We used alanine-scanning mutagenesis to generate IGF1R mutants and assessed their abundance and maturation, as well as the effect of mutation on RSV infection. We identified several mutations that appear to inhibit IGF1R maturation; but surprisingly, these mutations had no significant effect on RSV infection. This suggests that maturation of IGF1R may not be required for RSV infection. Additionally, we identified one residue, S788, that, when mutated, significantly reduced RSV infection. Further analysis revealed that this mutation disrupted a hydrogen bonding network that may be important for both IGF1R maturation and RSV infection.

Estimating the Lifetime Costs and Benefits of the Incredible Years Teacher Classroom Management Intervention Using Data From 30 Months Follow-Up of the Supporting Teachers and childRen in Schools Trial.

OBJECTIVES: The Incredible Years Teacher® Classroom Management (IY-TCM) intervention is associated with short-term improvements in mental health difficulties in young people. The aim was to estimate the long-term impact and cost-effectiveness of the IY-TCM intervention compared with no intervention. METHODS: An existing health economic model (LifeSim 1.0) was used to translate short-term changes in the Strength and Difficulties Questionnaire (SDQ), based on the Supporting Teachers and childRen in Schools cluster randomized controlled trial of the IY-TCM intervention in schools, into estimated medium- and long-term effects using multiple longitudinal data sets. LifeSim 1.0 was adapted to incorporate teacher-reported SDQ and account for individual heterogeneity. Cost-effectiveness analyses were conducted using the trial-based intervention cost with subgroup analyses on deprivation, conduct scores and parental depression in the simulated baseline population. RESULTS: Regression analyses show significant predictor variables for intervention effectiveness, including deprivation and baseline SDQ. LifeSim results indicate small gains in long-term outcomes, and cost-effective analyses estimated that the IY-TCM intervention could be cost-effective, but there was a large amount of uncertainty (net monetary benefit = £10, Estimated CI = -£134, £156). Benefits and certainty of cost-effectiveness were greater for some subgroups, such as those with high conduct scores at baseline (net monetary benefit = £206, Estimated CI = £26, £318). CONCLUSIONS: IY-TCM could be cost-effective, but there was a large amount of uncertainty around costs and benefits. Greater benefits for pupils with difficulties at baseline suggest that the intervention may be more cost-effective for schools in more deprived areas with high levels of conduct problems.

Is neighbourhood deprivation in primary school-aged children associated with their mental health and does this association change over 30 months?

As both socioeconomic deprivation and the prevalence of childhood mental health difficulties continue to increase, exploring the relationship between them is important to guide policy. We aimed to replicate the finding of a mental health gap that widened with age between those living in the most and least deprived areas among primary school pupils. We used data from 2075 children aged 4-9 years in the South West of England recruited to the STARS (Supporting Teachers and childRen in Schools) trial, which collected teacher- and parent-reported Strength and Difficulties Questionnaire (SDQ) at baseline, 18-month and 30-month follow-up. We fitted multilevel regression models to explore the relationship between Index of Multiple Deprivation (IMD) quintile and SDQ total difficulties score and an algorithm-generated "probable disorder" variable that combined SDQ data from teachers and parents. Teacher- and parent-reported SDQ total difficulties scores indicated worse mental health in children living in more deprived neighbourhoods, which was attenuated by controlling for special educational needs and disabilities but remained significant by parent report, and there was no interaction year group status (age) at baseline. We did not detect an association between probable disorder and IMD although an interaction with time was evident (p = 0.003). Analysis by study wave revealed associations at baseline (odds ratio 1.94, 95% confidence interval 0.97-3.89) and 18 months (1.96, 1.07-3.59) but not 30 months (0.94, 0.54-1.57). These findings augment the existing, highly compelling evidence demonstrating worse mental health in children exposed to socioeconomic deprivation.

The UK stand together trial: protocol for a multicentre cluster randomised controlled trial to evaluate the effectiveness and cost-effectiveness of KiVa to reduce bullying in primary schools.

BACKGROUND: Reducing bullying is a public health priority. KiVa, a school-based anti-bullying programme, is effective in reducing bullying in Finland and requires rigorous testing in other countries, including the UK. This trial aims to test the effectiveness and cost-effectiveness of KiVa in reducing child reported bullying in UK schools compared to usual practice. The trial is currently on-going. Recruitment commenced in October 2019, however due to COVID-19 pandemic and resulting school closures was re-started in October 2020. METHODS: Design: Two-arm pragmatic multicentre cluster randomised controlled trial with an embedded process and cost-effectiveness evaluation. PARTICIPANTS: 116 primary schools from four areas; North Wales, West Midlands, South East and South West England. Outcomes will be assessed at student level (ages 7-11 years; n = approximately 13,000 students). INTERVENTION: KiVa is a whole school programme with universal actions that places a strong emphasis on changing bystander behaviour alongside indicated actions that provide consistent strategies for dealing with incidents of bullying. KiVa will be implemented over one academic year. COMPARATOR: Usual practice. PRIMARY OUTCOME: Student-level bullying-victimisation assessed through self-report using the extensively used and validated Olweus Bully/Victim questionnaire at baseline and 12-month follow-up. SECONDARY OUTCOMES: student-level bullying-perpetration; student mental health and emotional well-being; student level of, and roles in, bullying; school related well-being; school attendance and academic attainment; and teachers' self-efficacy in dealing with bullying, mental well-being, and burnout. SAMPLE SIZE: 116 schools (58 per arm) with an assumed ICC of 0.02 will provide 90% power to identify a relative reduction of 22% with a 5% significance level. RANDOMISATION: recruited schools will be randomised on 1:1 basis stratified by Key-Stage 2 size and free school meal status. Process evaluation: assess implementation fidelity, identify influences on KiVa implementation, and examine intervention mechanisms. Economic evaluation: Self-reported victimisation, Child Health Utility 9D, Client Service Receipt Inventory, frequency of services used, and intervention costs. The health economic analysis will be conducted from a schools and societal perspective. DISCUSSION: This two-arm pragmatic multicentre cluster randomised controlled trial will evaluate the KiVa anti-bullying intervention to generate evidence of the effectiveness, cost-effectiveness and scalability of the programme in the UK. Our integrated process evaluation will assess implementation fidelity, identify influences on KiVa implementation across England and Wales and examine intervention mechanisms. The integrated health economic analysis will be conducted from a schools and societal perspective. Our trial will also provide evidence regarding the programme impact on inequalities by testing whether KiVa is effective across the socio-economic gradient. TRIAL REGISTRATION: Trials ISRCTN 12300853 Date assigned 11/02/2020.

Teachers' concerns about pupils' mental health in a cross-sectional survey of a population sample of British schoolchildren.

BACKGROUND: Schools are becoming central to the identification and referral of children and young people with poor mental health. Understanding how well a teacher concern predicts mental disorder in a child or young person is important for mental health teams who need to respond to referrals. METHOD: This secondary analysis of the 2004 British Child and Adolescent Mental Health Survey used the first item of the Strengths and Difficulties Questionnaire (SDQ) Impact subscale to indicate concern about a child or young person's mental health. Mental disorder according to DSM IVR criteria was assessed using the multi-informant Development and Well-Being Assessment. We compared the proportion with and without mental disorder according to the presence or absence of teacher concern. RESULTS: Teacher concern was moderately predictive (49% with teacher concern had a disorder) and sensitive (teacher concern present among 56% with disorder), while lack of teacher concern was highly predictive (only 5% had disorder) and specific (94% no disorder). Teacher concern was associated with significantly poorer mental health (mean teacher SDQ total difficulty score 19.6, SD 5.6 with disorder, mean 15.0; SD 5.1 if no disorder) compared to children without teacher concern (mean 9.6, SD 5.5 with disorder, and 4.9; SD 4.3 if no disorder; F (3, 5,931) = 1527.228, p = .001). If both teacher and parents were concerned, the child or young person was much more likely to have a disorder. CONCLUSION: A lack of teacher concern can reassure mental health practitioners in the vast majority of cases. While teacher concern does identify those with poorer mental health, it is only moderately predictive of a disorder. When concerned about a child or young person, discussions with parents or others who know them may help teachers identify those who most need support. KEY PRACTITIONER MESSAGE: The emphasis on schools as a major setting to provide support and identify the need for referral to specialist mental health services means service commissioners, providers and practitioners could benefit from insight into how predictive a teacher's concern is of childhood mental health conditions and how this may vary with the type of disorder If teachers are not concerned about a child, practitioners can be reassured that there is unlikely to be a significant problem with their mental health, although this will be less certain in schools whose pupils are likely to have a higher than average levels of difficulty Teacher concerns do not necessarily differentiate between clinically impairing and mild/ moderate mental health difficulties, but do identify children in poorer mental health Asking for corroboration of concern from other sources increases the strength of the association to severe mental health disorders.

The effectiveness and cost-effectiveness of the Incredible Years® Teacher Classroom Management programme in primary school children: results of the STARS cluster randomised controlled trial.

BACKGROUND: We evaluated the effectiveness and cost-effectiveness of the Incredible Years® Teacher Classroom Management (TCM) programme as a universal intervention, given schools' important influence on child mental health. METHODS: A two-arm, pragmatic, parallel group, superiority, cluster randomised controlled trial recruited three cohorts of schools (clusters) between 2012 and 2014, randomising them to TCM (intervention) or Teaching As Usual (TAU-control). TCM was delivered to teachers in six whole-day sessions, spread over 6 months. Schools and teachers were not masked to allocation. The primary outcome was teacher-reported Strengths and Difficulties Questionnaire (SDQ) Total Difficulties score. Random effects linear regression and marginal logistic regression models using Generalised Estimating Equations were used to analyse the outcomes. TRIAL REGISTRATION: ISRCTN84130388. RESULTS: Eighty schools (2075 children) were enrolled; 40 (1037 children) to TCM and 40 (1038 children) to TAU. Outcome data were collected at 9, 18, and 30-months for 96, 89, and 85% of children, respectively. The intervention reduced the SDQ-Total Difficulties score at 9 months (mean (s.d.):5.5 (5.4) in TCM v. 6.2 (6.2) in TAU; adjusted mean difference = -1.0; 95% CI-1.9 to -0.1; p = 0.03) but this did not persist at 18 or 30 months. Cost-effectiveness analysis suggested that TCM may be cost-effective compared with TAU at 30-months, but this result was associated with uncertainty so no firm conclusions can be drawn. A priori subgroup analyses suggested TCM is more effective for children with poor mental health. CONCLUSIONS: TCM provided a small, short-term improvement to children's mental health particularly for children who are already struggling.

Young infants' visual fixation patterns in addition and subtraction tasks support an object tracking account.

Investigating infants' numerical ability is crucial to identifying the developmental origins of numeracy. Wynn (1992) claimed that 5-month-old infants understand addition and subtraction as indicated by longer looking at outcomes that violate numerical operations (i.e., 1+1=1 and 2-1=2). However, Wynn's claim was contentious, with others suggesting that her results might reflect a familiarity preference for the initial array or that they could be explained in terms of object tracking. To cast light on this controversy, Wynn's conditions were replicated with conventional looking time supplemented with eye-tracker data. In the incorrect outcome of 2 in a subtraction event (2-1=2), infants looked selectively at the incorrectly present object, a finding that is not predicted by an initial array preference account or a symbolic numerical account but that is consistent with a perceptual object tracking account. It appears that young infants can track at least one object over occlusion, and this may form the precursor of numerical ability.

Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trial.

BACKGROUND: Individuals with a history of recurrent depression have a high risk of repeated depressive relapse or recurrence. Maintenance antidepressants for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to medication. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce risk of relapse or recurrence compared with usual care, but has not yet been compared with maintenance antidepressant treatment in a definitive trial. We aimed to see whether MBCT with support to taper or discontinue antidepressant treatment (MBCT-TS) was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months. METHODS: In this single-blind, parallel, group randomised controlled trial (PREVENT), we recruited adult patients with three or more previous major depressive episodes and on a therapeutic dose of maintenance antidepressants, from primary care general practices in urban and rural settings in the UK. Participants were randomly assigned to either MBCT-TS or maintenance antidepressants (in a 1:1 ratio) with a computer-generated random number sequence with stratification by centre and symptomatic status. Participants were aware of treatment allocation and research assessors were masked to treatment allocation. The primary outcome was time to relapse or recurrence of depression, with patients followed up at five separate intervals during the 24-month study period. The primary analysis was based on the principle of intention to treat. The trial is registered with Current Controlled Trials, ISRCTN26666654. FINDINGS: Between March 23, 2010, and Oct 21, 2011, we assessed 2188 participants for eligibility and recruited 424 patients from 95 general practices. 212 patients were randomly assigned to MBCT-TS and 212 to maintenance antidepressants. The time to relapse or recurrence of depression did not differ between MBCT-TS and maintenance antidepressants over 24 months (hazard ratio 0·89, 95% CI 0·67-1·18; p=0·43), nor did the number of serious adverse events. Five adverse events were reported, including two deaths, in each of the MBCT-TS and maintenance antidepressants groups. No adverse events were attributable to the interventions or the trial. INTERPRETATION: We found no evidence that MBCT-TS is superior to maintenance antidepressant treatment for the prevention of depressive relapse in individuals at risk for depressive relapse or recurrence. Both treatments were associated with enduring positive outcomes in terms of relapse or recurrence, residual depressive symptoms, and quality of life. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula.

Nondepolarizing Neuromuscular Blocking Agents, Reversal, and Risk of Postoperative Pneumonia.

BACKGROUND: Residual postoperative paralysis from nondepolarizing neuromuscular blocking agents (NMBAs) is a known problem. This paralysis has been associated with impaired respiratory function, but the clinical significance remains unclear. The aims of this analysis were two-fold: (1) to investigate if intermediate-acting NMBA use during surgery is associated with postoperative pneumonia and (2) to investigate if nonreversal of NMBAs is associated with postoperative pneumonia. METHODS: Surgical cases (n = 13,100) from the Vanderbilt University Medical Center National Surgical Quality Improvement Program database who received general anesthesia were included. The authors compared 1,455 surgical cases who received an intermediate-acting nondepolarizing NMBA to 1,455 propensity score-matched cases who did not and 1,320 surgical cases who received an NMBA and reversal with neostigmine to 1,320 propensity score-matched cases who did not receive reversal. Postoperative pneumonia incidence rate ratios (IRRs) and bootstrapped 95% CIs were calculated. RESULTS: Patients receiving an NMBA had a higher absolute incidence rate of postoperative pneumonia (9.00 vs. 5.22 per 10,000 person-days at risk), and the IRR was statistically significant (1.79; 95% bootstrapped CI, 1.08 to 3.07). Among surgical cases who received an NMBA, cases who were not reversed were 2.26 times as likely to develop pneumonia after surgery compared to cases who received reversal with neostigmine (IRR, 2.26; 95% bootstrapped CI, 1.65 to 3.03). CONCLUSIONS: Intraoperative use of intermediate nondepolarizing NMBAs is associated with developing pneumonia after surgery. Among patients who receive these agents, nonreversal is associated with an increased risk of postoperative pneumonia.

Insurance status influences emergent designation in surgical transfers.

BACKGROUND: There is a perception among surgeons that hospitals disproportionately transfer unfavorably insured patients for emergency surgical care. Emergency medical condition (EMC) designation mandates referral center acceptance of patients for whom transfer is requested. We sought to understand whether unfavorably insured patients are more likely to be designated as EMCs. MATERIALS AND METHODS: A retrospective cohort study was performed on patient transfers from a large network of acute care facilities to emergency surgery services at a tertiary referral center from 2009-2013. Insurance was categorized as favorable (commercial or Medicare) or unfavorable (Medicaid or uninsured). The primary outcome, transfer designation as EMC or non-EMC, was evaluated using multivariable logistic regression. A secondary analysis evaluated uninsured patients only. RESULTS: There were 1295 patient transfers in the study period. Twenty percent had unfavorable insurance. Favorably insured patients were older with fewer nonwhite, more comorbidities, greater illness severity, and more likely transferred for care continuity. More unfavorably insured patients were designated as EMCs (90% versus 84%, P < 0.01). In adjusted models, there was no association between unfavorable insurance and EMC transfer (odds ratio [OR], 1.61; 95% confidence interval [CI], 0.98-2.69). Uninsured patients were more likely to be designated as EMCs (OR, 2.27; CI, 1.08-4.77). CONCLUSIONS: The finding that uninsured patients were more likely to be designated as EMCs suggests nonclinical variation that may be mitigated by clearer definitions and increased interfacility coordination to identify patients requiring transfer for EMCs.

The effect of regulatory advisories on maternal antidepressant prescribing, 1995-2007: an interrupted time series study of 228,876 pregnancies.

The purpose of this study was to assess whether antidepressant prescribing during pregnancy decreased following release of U.S. and Canadian public health advisory warnings about the risk of perinatal complications with antidepressants. We analyzed data from 228,876 singleton pregnancies among women (aged 15-44 years) continuously enrolled in Tennessee Medicaid with full pharmacy benefits (1995-2007). Antidepressant prescribing was determined through outpatient pharmacy dispensing files. Information on sociodemographic and clinical factors was obtained from enrollment files and linked birth certificates. An interrupted time series design with segmented regression analysis was used to quantify the impact of the advisory warnings (2002-2005). Antidepressant prescribing rates increased steadily from 1995 to 2001, followed by sharper increases from 2002 to late 2004. Overall antidepressant prescribing prevalence was 34.51 prescriptions [95 % confidence interval (CI) 33.37-35.65] per 1,000 women in January 2002, and increased at a rate of 0.46 (95 % CI 0.41-0.52) prescriptions per 1,000 women per month until the end of the pre-warning period (May 2004). During the post-warning period (October 2004-June 2005), antidepressant prescribing decreased by 1.48 (95 % CI 1.62-1.35) prescriptions per 1,000 women per month. These trends were observed for both selective serotonin reuptake inhibitors (SSRI) and non-SSRI antidepressants, although SSRI prescribing decreased at a greater rate. We conclude that antidepressant prescribing to pregnant women in Tennessee Medicaid increased from 1995 to late 2004. U.S. and Canadian public health advisories about antidepressant-associated perinatal complications were associated with steady decreases in antidepressant prescribing from late 2004 until the end of the study period, suggesting that the advisory warnings were impactful on antidepressant prescribing in pregnancy.

The Mental Wellbeing of Child and Adolescent Mental Health Service (CAMHS) Workers in England: A Cross-Sectional Descriptive Study Reporting Levels of Burnout, Wellbeing and Job Satisfaction.

In the UK, there has been a notable increase in referrals to specialist children's mental health services. This, coupled with shortages of qualified staff, has raised concerns about the escalating occupational stress experienced by staff in this sector. In this brief report, we present cross-sectional quantitative data from 97 staff members working in one Child and Adolescent Mental Health Service (CAMHS) in the UK during spring 2023, reporting on their wellbeing, job satisfaction, and burnout. Our findings reveal that over a third of CAMHS staff experienced moderate or high levels of work-related burnout; 39% reported moderate or high levels of personal burnout, but levels of client-related burnout were much lower (13%). Both work- and client-related burnout showed a robust negative relationship with job satisfaction, with higher burnout predicting lower levels of job satisfaction. Only a small proportion of respondents reported high levels of wellbeing, with about a quarter experiencing levels of wellbeing that can be considered indicative of mild or clinical depressive symptoms. Whilst these results are from a small sample in one area of the UK, they present an important snapshot of CAMHS staff wellbeing and are discussed in the context of similar trends reported in the wider NHS sector.

Increased healthcare resource utilization for acute respiratory illness among Latino infants.

OBJECTIVE: To examine healthcare resource utilization for acute respiratory illness in Latino infants compared with other racial/ethnic groups. STUDY DESIGN: We studied 674 term-born, previously healthy infants brought in for an unscheduled healthcare visit for an acute respiratory illness. The predictor variable was infant race/ethnicity, and the primary outcome was healthcare resource utilization, adjusted for age and disease severity. RESULTS: The cohort was 14% Latino, 52% white, 22% African American, and 12% other race/ethnicity. More than one-third (37%) of the mothers of Latino infants were Spanish-speaking. The bronchiolitis severity score was higher (indicating more severe disease) in white infants (median, 6.0; IQR, 3.0-9.0 on a scale of 0-12) compared with Latino (median, 3.0; IQR, 1.0-6.0) and African American (median, 3.5; IQR, 1.0-6.0) infants (P < .001 for the comparison of all groups). Disease severity was similar in Latino and African American infants (P = .96). Latino infants were the most likely to receive antibiotics (58%, compared with 47% of whites and 34% of African Americans; P = .005) and to have body fluid cultures drawn. Latino infants also were more likely than African American infants to undergo chest radiography and respiratory virus rapid antigen testing (P ≤ .01). Latino infants from Spanish-speaking families had a higher rate of respiratory syncytial virus testing compared with those from English-speaking families (76% vs 51%; P = .016). CONCLUSION: Providers caring for Latino infants with acute respiratory illness ordered more antibiotics and diagnostic testing for this group, particularly compared with African Americans, even though the 2 groups had similar disease severity and socioeconomic disparities. Language barrier may be a possible explanation for these differences.

Investigation of the feasibility and acceptability of a school-based intervention for children with traits of ADHD: protocol for an iterative case-series study.

INTRODUCTION: Attention deficit/hyperactivity disorder (ADHD) is a prevalent and impairing cluster of traits affecting 2%-5% of children. These children are at risk of negative health, social and educational outcomes and often experience severe difficulties at school, so effective psychosocial interventions are needed. There is mixed evidence for existing school-based interventions for ADHD, which are complex and resource-intensive, contradicting teachers' preferences for short, flexible strategies that suit a range of ADHD-related classroom-based problems. They are also poorly evaluated. In this study, a prototype intervention comprising a digital 'toolkit' of behavioural strategies will be tested and refined. We aim to refine the prototype so that its use is feasible and acceptable within school settings, and to establish whether a future definitive, appropriately powered, trial of effectiveness is feasible. This novel iterative study aims to pre-emptively address implementation and evaluation challenges that have hampered previous randomised controlled trials of non-pharmacological interventions. METHODS AND ANALYSIS: A randomised iterative mixed-methods case-series design will be used. Schools will be randomised to the time (school term) they implement the toolkit. Eight primary schools and 16-32 children with impairing traits of ADHD will participate, along with school staff and parents. The toolkit will be refined after each term, or more frequently if needed. Small, theory-based and data driven changes hypothesised as relevant across school contexts will be made, as well as reactive changes addressing implementation barriers. Feasibility and acceptability will be assessed through quantitative and qualitative data collection and analyses in relation to study continuation criteria, and ADHD symptoms and classroom functioning will be tracked and visually evaluated to assess whether there are early indications of toolkit utility. ETHICS AND DISSEMINATION: Ethical approval has been obtained. Results will be presented in journal articles, conferences and through varied forms of media to reach policymakers, stakeholders and the public.

Associations between School-Level Disadvantage, Bullying Involvement and Children's Mental Health.

Bullying is a modifiable risk factor for poor mental health across childhood and adolescence. It is also socially patterned, with increased prevalence rates in more disadvantaged settings. The current study aimed to better understand whether school-level disadvantage is associated with different types of bullying roles, and whether it is a moderator in the association between bullying and children's mental health. Cross-sectional data were used from 4727 children aged 6-11 years, from 57 primary schools across England and Wales. The child data included previous bullying involvement and bullying role characteristics (bully, victim, bully-victim, reinforcer, defender, outsider), and the teacher-reported data included each child's mental health (emotional symptoms and externalizing) problems. School-level disadvantage was calculated from the proportion of children in the school eligible to receive free school meals (an indicator of disadvantage). Children in more disadvantaged schools were more likely to report being bully perpetrators, bully-victims, and engage less in defending behaviors during a bullying incident. Children from more disadvantaged schools who reported bullying others showed fewer emotional symptoms than those from less disadvantaged schools. There was no other evidence of moderation by school-level disadvantage between bullying roles and emotional and externalizing problems. The findings highlight the potential for school-based interventions targeting children's emotional and social development, targeting bullying, and promoting defending behaviors, particularly in more disadvantaged settings.

The development and internal evaluation of a predictive model to identify for whom Mindfulness-Based Cognitive Therapy (MBCT) offers superior relapse prevention for recurrent depression versus maintenance antidepressant medication.

Depression is highly recurrent, even following successful pharmacological and/or psychological intervention. We aimed to develop clinical prediction models to inform adults with recurrent depression choosing between antidepressant medication (ADM) maintenance or switching to Mindfulness-Based Cognitive Therapy (MBCT). Using data from the PREVENT trial (N=424), we constructed prognostic models using elastic net regression that combined demographic, clinical and psychological factors to predict relapse at 24 months under ADM or MBCT. Only the ADM model (discrimination performance: AUC=.68) predicted relapse better than baseline depression severity (AUC=.54; one-tailed DeLong's test: z=2.8, p=.003). Individuals with the poorest ADM prognoses who switched to MBCT had better outcomes compared to those who maintained ADM (48% vs. 70% relapse, respectively; superior survival times [z=-2.7, p=.008]). For individuals with moderate-to-good ADM prognosis, both treatments resulted in similar likelihood of relapse. If replicated, the results suggest that predictive modeling can inform clinical decision-making around relapse prevention in recurrent depression.

Randomized trial of automated, electronic monitoring to facilitate early detection of sepsis in the intensive care unit*.

OBJECTIVE: To determine whether automated identification with physician notification of the systemic inflammatory response syndrome in medical intensive care unit patients expedites early administration of new antibiotics or improvement of other patient outcomes in patients with sepsis. DESIGN: : A prospective randomized, controlled, single center study. SETTING: Medical intensive care unit of an academic, tertiary care medical center. PATIENTS: Four hundred forty-two consecutive patients admitted over a 4-month period who met modified systemic inflammatory response syndrome criteria in a medical intensive care unit. INTERVENTION: Patients were randomized to monitoring by an electronic "Listening Application" to detect modified (systemic inflammatory response syndrome) criteria vs. usual care. The listening application notified physicians in real time when modified systemic inflammatory response syndrome criteria were detected, but did not provide management recommendations. MEASUREMENTS AND MAIN RESULTS: The median time to new antibiotics was similar between the intervention and usual care groups when comparing among all patients (6.0 hr vs. 6.1 hr, p = .95), patients with sepsis (5.3 hr vs. 5.1 hr; p = .90), patients on antibiotics at enrollment (5.2 hr vs. 7.0 hr, p = .27), or patients not on antibiotics at enrollment (5.2 hr vs. 5.1 hr, p = .85). The amount of fluid administered following detection of modified systemic inflammatory response syndrome criteria was similar between groups whether comparing all patients or only patients who were hypotensive at enrollment. Other clinical outcomes including intensive care unit length of stay, hospital length of stay, and mortality were not shown to be different between patients in the intervention and control groups. CONCLUSIONS: Realtime alerts of modified systemic inflammatory response syndrome criteria to physicians in one tertiary care medical intensive care unit were feasible and safe but did not influence measured therapeutic interventions for sepsis or significantly alter clinical outcomes.

Maternal antidepressant use and adverse outcomes: a cohort study of 228,876 pregnancies.

OBJECTIVE: The purpose of this study was to describe antidepressant medication use patterns during pregnancy and pregnancy outcomes. STUDY DESIGN: We evaluated a cohort of 228,876 singleton pregnancies that were covered by Tennessee Medicaid, 1995-2007. RESULTS: Of 23,280 pregnant women with antidepressant prescriptions before pregnancy, 75% of them filled none in the second or third trimesters of pregnancy, and 10.7% of them used antidepressants throughout pregnancy. Filling 1, 2, and ≥3 antidepressant prescriptions during the second trimester was associated with shortened gestational age by 1.7 (95% confidence interval [CI], 1.2-2.3), 3.7 (95% CI, 2.8-4.6), and 4.9 (95% CI, 3.9-5.8) days, when controlled for measured confounders. Third-trimester selective serotonin reuptake inhibitor use was associated with infant convulsions; adjusted odds ratios were 1.4 (95% CI, 0.7-2.8); 2.8 (95% CI, 1.9-5.5); and 4.9 (95% CI, 2.6-9.5) for filling 1, 2, and ≥3 prescriptions, respectively. CONCLUSION: Most women discontinue antidepressant medications before or during the first trimester of pregnancy. Second-trimester antidepressant use is associated with preterm birth, and third-trimester selective serotonin reuptake inhibitor use is associated with infant convulsions.

Synthesising the existing evidence for non-pharmacological interventions targeting outcomes relevant to young people with ADHD in the school setting: systematic review protocol.

BACKGROUND: Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) have impairing levels of difficulty paying attention, impulsive behaviour and/or hyperactivity. ADHD causes extensive difficulties for young people at school, and as a result these children are at high risk for a wide range of poor outcomes. We ultimately aim to develop a flexible, modular 'toolkit' of evidence-based strategies that can be delivered by primary school staff to improve the school environment and experience for children with ADHD; the purpose of this review is to identify and quantify the evidence-base for potential intervention components. This protocol sets out our plans to systematically identify non-pharmacological interventions that target outcomes that have been reported to be of importance to key stakeholders (ADHD symptoms, organisation skills, executive-global- and classroom-functioning, quality of life, self-esteem and conflict with teachers and peers). We plan to link promising individual intervention components to measured outcomes, and synthesise the evidence of effectiveness for each outcome. METHODS: A systematic search for studies published from the year 2000 that target the outcomes of interest in children and young people aged 3-12 will be conducted. Titles and abstracts will be screened using prioritisation software, and then full texts of potentially eligible studies will be screened. Systematic reviews, RCTs, non-randomised and case-series studies are eligible designs. Synthesis will vary by the type of evidence available, potentially including a review of reviews, meta-analysis and narrative synthesis. Heterogeneity of studies meta-analysed will be assessed, along with publication bias. Intervention mapping will be applied to understand potential behaviour change mechanisms for promising intervention components. DISCUSSION: This review will highlight interventions that appear to effectively ameliorate negative outcomes that are of importance for people with ADHD, parents, school staff and experts. Components of intervention design and features that are associated with effective change in the outcome will be delineated and used to inform the development of a 'toolkit' of non-pharmacological strategies that school staff can use to improve the primary school experience for children with ADHD. TRIAL REGISTRATION: PROSPERO number CRD42021233924.

Teachers' views on the acceptability and implementation of the Incredible Years® Teacher Classroom Management programme in English (UK) primary schools from the STARS trial.

BACKGROUND: The Incredible Years® (IY) Teacher Classroom Management (TCM) programme may reduce disruptive behaviour in the classroom and improve child and teacher mental health; however, few studies have considered how acceptable TCM is to teachers or what facilitators and barriers there are to its implementation. AIMS: In this paper we examine the acceptability of the full 6-day TCM programme and teachers' perceived barriers and facilitators to implementation in the English (UK) primary school context. SAMPLE: Forty-four English (UK) primary school teachers who attended the TCM programme as part of the STARS trial. METHODS: We completed focus groups and telephone interviews with participating teachers 2 months after they completed the TCM programme. Thematic analysis was used to examine the data, and a framework approach was applied to organize and summarize themes. RESULTS: Teachers liked the structure of the course, the peer group learning environment, delivery methods, and the opportunity to reflect outside the classroom on their practice. They reported that the video clips used lacked cultural relevance and highlighted the importance of group leadership style. Perceived facilitators to implementation included an understanding of the theory underpinning TCM and adaptability of the TCM strategies. Barriers included perceived gaps in the course content in relation to challenging behaviour, applying strategies with older children and the school context within which teachers were working. CONCLUSION: Our findings suggest high levels of acceptability to TCM overall, but also highlight the need for a whole school approach to combat potential barriers to implementation.