Evaluation of Continuous Infusion Vancomycin in a Pediatric Hematology/Oncology Population.

BACKGROUND: Continuous infusion vancomycin (CIV) may benefit children who are unable to achieve therapeutic concentrations with intermittent vancomycin dosing and may facilitate outpatient administration by alleviating the burden of frequent dosing intervals. Previous studies have used variable dosing regimens and steady-state concentration goals. The purpose of this study was to evaluate the total daily dose (TDD) of CIV required to achieve therapeutic steady-state concentrations of 15-25 µg/mL in pediatric hematology/oncology patients. METHODS: A single-center retrospective study was performed for patients treated with CIV from January 2017 to June 2019. The primary outcome was the TDD required to achieve therapeutic steady-state concentrations on CIV. Secondary outcomes included time to reach therapeutic steady-state concentrations, CIV indications and adverse events associated with CIV. RESULTS: Data were collected for 71 courses of CIV in 60 patients. Median patient age was 4 years (range: 0.4-20 years). The median TDD required to achieve initial therapeutic concentrations was 50.3 mg/kg/d (interquartile range: 38.8-59.2) and was further divided into age-based cohorts. TDD in mg/kg was significantly lower in the older cohort ( P < 0.001), but there was no statistically significant difference between age-based cohorts with TDD in mg/m 2 ( P = 0.97). Median time to achieve first therapeutic concentration was 19.3 hours (range: 8.6-72.3 hours). The most common indication for CIV was ease of outpatient administration (69.0%). Acute kidney injury incidence was minimal (4.2%). CONCLUSIONS: CIV is associated with rapid attainment of target concentrations in pediatric hematology/oncology patients and is safe and well tolerated.

Teachers as first responders: classroom experiences and mental health training needs of Australian schoolteachers.

BACKGROUND: Schoolteachers are often the first to respond when a student presents with a mental health issue in the classroom. This places a burden on schools that impacts school staff, healthcare workers and teachers. More broadly, it places a responsibility on the education system to address students' mental health. This study examines Australian teachers' classroom experiences and the training areas identified by teachers as necessary to manage these issues. METHOD: Interviews were undertaken with 18 in-service teachers between 2020 and 2021 from Catholic, Independent and Public schools. Data were gathered via multiple interviews and analysed using thematic content analysis. RESULTS: The major mental health issues identified by teachers related to mental disorders, depression, anxiety, and a complex range of negative emotional states. Teachers requested training in child and adolescent mental health, counselling skills, early detection and intervention, and training skills to manage the complex relationship with parents and external health and community personnel. Teachers also reported the need to access mental health resources, support and training, which were differentially accessed along socioeconomic status and postcodes. CONCLUSION: The data show that teachers are often placed as first responders when a student has a mental health issue but feel inadequately trained to manage these issues in the classroom. We identified mental health issues presenting in Australian classrooms and documented critical features of mental-health training asked for by teachers in order to address those issues. Given the increasing demands on teachers to address the mental health of children and adolescents, we argue that an urgent review of mental health training for teachers is needed.

Prospective External Validation of the Esbenshade Vanderbilt Models Accurately Predicts Bloodstream Infection Risk in Febrile Non-Neutropenic Children With Cancer.

PURPOSE: The optimal management of fever without severe neutropenia (absolute neutrophil count [ANC] ≥500/µL) in pediatric patients with cancer is undefined. The previously proposed Esbenshade Vanderbilt (EsVan) models accurately predict bacterial bloodstream infections (BSIs) in this population and provide risk stratification to aid management, but have lacked prospective external validation. MATERIALS AND METHODS: Episodes of fever with a central venous catheter and ANC ≥500/µL occurring in pediatric patients with cancer were prospectively collected from 18 academic medical centers. Variables included in the EsVan models and 7-day clinical outcomes were collected. Five versions of the EsVan models were applied to the data with calculation of C-statistics for both overall BSI rate and high-risk organism BSI (gram-negative and Staphylococcus aureus BSI), as well as model calibration. RESULTS: In 2,565 evaluable episodes, the BSI rate was 4.7% (N = 120). Complications for the whole cohort were rare, with 1.1% (N = 27) needing intensive care unit (ICU) care by 7 days, and the all-cause mortality rate was 0.2% (N = 5), with only one potential infection-related death. C-statistics ranged from 0.775 to 0.789 for predicting overall BSI, with improved accuracy in predicting high-risk organism BSI (C-statistic 0.800-0.819). Initial empiric antibiotics were withheld in 14.9% of episodes, with no deaths or ICU admissions attributable to not receiving empiric antibiotics. CONCLUSION: The EsVan models, especially EsVan2b, perform very well prospectively across multiple academic medical centers and accurately stratify risk of BSI in episodes of non-neutropenic fever in pediatric patients with cancer. Implementation of routine screening with risk-stratified management for non-neutropenic fever in pediatric patients with cancer could safely reduce unnecessary antibiotic use.

Developing a Theory of Change for a Digital Youth Mental Health Service (Moderated Online Social Therapy): Mixed Methods Knowledge Synthesis Study.

BACKGROUND: Common challenges in the youth mental health system include low access, poor uptake, poor adherence, and limited overall effectiveness. Digital technologies offer promise, yet challenges in real-world integration and uptake persist. Moderated Online Social Therapy (MOST) aims to overcome these problems by integrating a comprehensive digital platform into existing youth mental health services. Theory of change (ToC) frameworks can help articulate how and why complex interventions work and what conditions are required for success. OBJECTIVE: The objective of this study is to create a ToC for MOST to explain how it works, why it works, who benefits and how, and what conditions are required for its success. METHODS: We used a multimethod approach to construct a ToC for MOST. The synthesis aimed to assess the real-world impact of MOST, a digital platform designed to enhance face-to-face youth mental health services, and to guide its iterative refinement. Data were gathered from 2 completed and 4 ongoing randomized controlled trials, 11 pilot studies, and over 1000 co-design sessions using MOST. Additionally, published qualitative findings from diverse clinical contexts and a review of related digital mental health literature were included. The study culminated in an updated ToC framework informed by expert feedback. The final ToC was produced in both narrative and table form and captured components common in program logic and ToC frameworks. RESULTS: The MOST ToC captured several assumptions about digital mental health adoption, including factors such as the readiness of young people and service providers to embrace digital platforms. External considerations included high service demand and a potential lack of infrastructure to support integration. Young people and service providers face several challenges and pain points MOST seeks to address, such as limited accessibility, high demand, poor engagement, and a lack of personalized support. Self-determination theory, transdiagnostic psychological treatment approaches, and evidence-based implementation theories and their associated mechanisms are drawn upon to frame the intervention components that make up the platform. Platform usage data are captured and linked to short-, medium-, and long-term intended outcomes, such as reductions in mental health symptoms, improvements in functioning and quality of life, reductions in hospital visits, and reduced overall mental health care costs. CONCLUSIONS: The MOST ToC serves as a strategic framework for refining MOST over time. The creation of the ToC helped guide the development of therapeutic content personalization, user engagement enhancement, and clinician adoption through specialized implementation frameworks. While powerful, the ToC approach has its limitations, such as a lack of standardized methodology and the amount of resourcing required for its development. Nonetheless, it provides an invaluable roadmap for iterative development, evaluation, and scaling of MOST and offers a replicable model for other digital health interventions aiming for targeted, evidence-based impact.

Cefiderocol Red Wine Urine Syndrome in Pediatric Patients: A Multicenter Case Series.

Cefiderocol is a novel cephalosporin antibiotic with activity against multidrug-resistant gram-negative bacteria and limited pediatric experience. This case series describes 3 immunocompromised children receiving blood transfusion who developed benign red or purple urine with administration of cefiderocol. Interaction with iron from blood products is a possible mechanism. It is important to recognize this phenomenon and distinguish it from hematuria to avoid unnecessary diagnostic testing.

Digital Application of Clinical Staging to Support Stratification in Youth Mental Health Services: Validity and Reliability Study.

BACKGROUND: As the demand for youth mental health care continues to rise, managing wait times and reducing treatment delays are key challenges to delivering timely and quality care. Clinical staging is a heuristic model for youth mental health that can stratify care allocation according to individuals' risk of illness progression. The application of staging has been traditionally limited to trained clinicians yet leveraging digital technologies to apply clinical staging could increase the scalability and usability of this model in services. OBJECTIVE: The aim of this study was to validate a digital algorithm to accurately differentiate young people at lower and higher risk of developing mental disorders. METHODS: We conducted a study with a cohort comprising 131 young people, aged between 16 and 25 years, who presented to youth mental health services in Australia between November 2018 and March 2021. Expert psychiatrists independently assigned clinical stages (either stage 1a or stage 1b+), which were then compared to the digital algorithm's allocation based on a multidimensional self-report questionnaire. RESULTS: Of the 131 participants, the mean age was 20.3 (SD 2.4) years, and 72% (94/131) of them were female. Ninety-one percent of clinical stage ratings were concordant between the digital algorithm and the experts' ratings, with a substantial interrater agreement (κ=0.67; P<.001). The algorithm demonstrated an accuracy of 91% (95% CI 86%-95%; P=.03), a sensitivity of 80%, a specificity of 93%, and an F1-score of 73%. Of the concordant ratings, 16 young people were allocated to stage 1a, while 103 were assigned to stage 1b+. Among the 12 discordant cases, the digital algorithm allocated a lower stage (stage 1a) to 8 participants compared to the experts. These individuals had significantly milder symptoms of depression (P<.001) and anxiety (P<.001) compared to those with concordant stage 1b+ ratings. CONCLUSIONS: This novel digital algorithm is sufficiently robust to be used as an adjunctive decision support tool to stratify care and assist with demand management in youth mental health services. This work could transform care pathways and expedite care allocation for those in the early stages of common anxiety and depressive disorders. Between 11% and 27% of young people seeking care may benefit from low-intensity, self-directed, or brief interventions. Findings from this study suggest the possibility of redirecting clinical capacity to focus on individuals in stage 1b+ for further assessment and intervention.

SARS-CoV-2 infection in high-risk children following tixagevimab-cilgavimab (Evusheld) pre-exposure prophylaxis: a single-center observational study.

From 8 December 2021 to 26 January 2023, tixagevimab-cilgavimab (T-C) was authorized for pre-exposure prophylaxis of COVID-19. During this period, we used a multidisciplinary team to communicate, screen, approach, and administer T-C to eligible patients. Twenty-seven patients were eligible. Of these, 24 (88.9%) received at least one dose of T-C and three patients received two doses. Majority of patients were White, non-Hispanic, and women. Only two patients had COVID-19 prior to receiving T-C. Seventeen (70.8%) had received two or more doses of SARS-CoV-2 vaccine. No serious adverse events were noted. Seven patients developed SARS-CoV-2 infection within 180 days of receiving T-C (median 102 days; range 28-135), and only one patient developed severe COVID-19 requiring intensive mechanical ventilation in the intensive care unit.

An open trial of the feasibility of brief internet-delivered acceptance and aommitment therapy (iACT) for chronic anxiety and depression.

Anxiety and depressive disorders are common, often chronic and result in significant disability and distress. The delivery of psychological interventions via the internet is now recognised to be a safe and effective way to treat these disorders. The predominant therapeutic model in clinical trials and in routine care has been cognitive-behavioural therapy (CBT), which helps patients identify and modify unhelpful thoughts and behaviours. However, other models of treatment for anxiety and depression, such as acceptance and commitment therapy (ACT), which uses the examination of both positive and negative experiences in the service of living a personally meaningful and values-based life, have been developed and tested, although most of these interventions are long and require more clinician support to ensure adherence and achieve positive outcomes. The aim of the present study was to examine the feasibility of a new brief, clinician supported transdiagnostic internet-delivered (iACT) program, designed to treat symptoms of both anxiety and depression and improve social function. A single-group open trial was conducted on 24 adults with long-term symptoms of anxiety and depression. The course is comprised of five online modules delivered over 8 weeks either self-guided or with support from a clinician. There was a high course completion rate (70 %) and a high level of satisfaction with the course (94 % satisfied or very satisfied). Significant clinical improvement in our primary outcome measures (within-group Cohen's d) of anxiety (d ≥ 0.62), depression (d ≥ 0.63), disability (d ≥ 0.43) and quality of life (d ≥ -0.57) were observed at posttreatment. Relatively little clinician time was required per participant (M = 30.6 min, SD = 5.7). The findings of the current study support the feasibility and potential of a transdiagnostic iACT treatment for adults experiencing long-term symptoms of anxiety and depression, including those patients who have not derived benefit from other treatments.

Evaluation of a therapist-guided virtual psychological pain management program when provided as routine care: a prospective pragmatic cohort study.

INTRODUCTION: Numerous randomized controlled trials have evaluated the outcomes of internet-delivered psychological pain management programs (PMPs) as a way of increasing access to care for people with chronic pain. However, there are few reports of the effectiveness of these PMPs when provided as part of routine care. METHODS: The present study sought to report the clinical and demographic characteristics of users (n = 1367) and examine the effectiveness of an established internet-delivered psychological PMP program in improving several pain-related outcomes, when offered at a national digital mental health service over a 5-year period. It also sought to comprehensively explore predictors of treatment commencement, treatment completion, and clinical improvement. RESULTS: Evidence of clinical improvements (% improvement; Hedges g) were found for all outcomes, including pain interference (18.9%; 0.55), depression (26.1%; 0.50), anxiety (23.9%; 0.39), pain intensity (12.8%; 0.41), pain self-efficacy (-23.8%; -0.46) and pain-catastrophizing (26.3%; 0.56). A small proportion of users enrolled but did not commence treatment (13%), however high levels of treatment completion (whole treatment = 63%; majority of the treatment = 75%) and satisfaction (very satisfied = 45%; satisfied = 37%) were observed among those who commenced treatment. There were a number of demographic and clinical factors associated with commencement, completion and improvement, but no decisive or dominant predictors were observed. DISCUSSION: These findings highlight the effectiveness and acceptability of internet-delivered psychological PMPs in routine care and point to the need to consider how best to integrate these interventions into the pathways of care for people with chronic pain.

Efficacy and Effectiveness of Universal School-Based Wellbeing Interventions in Australia: A Systematic Review.

The World Health Organisation defines health in terms of wellbeing, and wellbeing has become both a construct and a measure of impact in early intervention and prevention programs in schools. In Australia, schools report on their wellbeing initiatives and there is a plethora of government-funded wellbeing programs already in place in schools. However, education systems and stakeholders worldwide are facing significant challenges with mixed evaluation results of program impact and intervention effect. To better support students, schools, school-based healthcare workers, and community, it is important to know about the effectiveness of school-based programs; yet in the last decade, there has been no national appraisal of these programs in Australia. This systematic review aims to report on the effectiveness of Australian school-based wellbeing programs through a search of 13 databases. Out of 2888 articles, 29 met inclusion criteria. The results found that seventeen interventions comprising 80% of the total number of participants reported no statistically significant intervention effect on wellbeing outcomes. We argue that supporting wellbeing through robust program intervention is important as wellbeing presents both an indication of later onset of more serious mental health issues, and an opportunity for early intervention to break the trajectory leading to full disorder.

Healthcare-Associated Infections Caused by Mycolicibacterium neoaurum.

Mycolicibacterium neoaurum is a rapidly growing mycobacterium and an emerging cause of human infections. M. neoaurum infections are uncommon but likely underreported, and our understanding of the disease spectrum and optimum management is incomplete. We summarize demographic and clinical characteristics of a case of catheter-related M. neoaurum bacteremia in a child with leukemia and those of 36 previously reported episodes of M. neoaurum infection. Most infections occurred in young to middle-aged adults with serious underlying medical conditions and commonly involved medical devices. Overall, infections were not associated with severe illness or death. In contrast to other mycobacteria species, M. neoaurum was generally susceptible to multiple antimicrobial drugs and responded promptly to treatment, and infections were associated with good outcomes after relatively short therapy duration and device removal. Delays in identification and susceptibility testing were common. We recommend using combination antimicrobial drug therapy and removal of infected devices to eradicate infection.

Circumstances of suicide after registration with a national digital mental health service: an analysis of coroners' reports.

BACKGROUND: Little is known about the safety of mental healthcare provided remotely by digital mental health services (DMHS), which do not offer face-to-face contact. AIMS: To examine the circumstances of suicide by patients registered with a national DMHS. METHOD: Data from 59 033 consenting patients registered with a national DMHS, the MindSpot Clinic, between 1 January 2013 and 31 December 2016 were linked with the Australian National Death Index and documents held by the National Coronial Information System (NCIS). Data extracted included demographic information, the nature of contact, duration between last contact and death, symptom scores and information in police, autopsy, toxicology and coroners' reports. RESULTS: Of the 59 033 patients, 90 (0.15%) died by suicide in a follow-up period of up to 5 years. The mean time between last contact and death was 560 days. Coroners' reports were located for 81/90 patients. Most (87.0%) were receiving face-to-face care around the time of death, 60.9% had a documented previous suicide attempt, 52.2% had been in hospital in the previous 6 months and 22.2% had severe mental illness, mainly schizophrenia or bipolar disorder. Other common findings were current treatment with psychotropic medication (79.2%) and the presence of alcohol (41.6%), benzodiazepines (31.2%), and illegal drugs and non-prescribed opioids (20.8%) at time of death. CONCLUSIONS: Those who died by suicide after contact with the DMHS had more severe illness, were mostly engaged with face-to-face services and often had disinhibiting substances, especially benzodiazepines, present at the time of death.

Integrating digital interventions with clinical practice in youth mental health services.

OBJECTIVE: Integrating digital technologies with clinical practice promises to improve access and enhance care in the context of high service demand and constrained capacity. METHOD: We outline the emerging research in the integration of digital tools in clinical care, known as blended care, and provide case examples of mental health technology platforms currently in use, summarise findings regarding novel technologies such as virtual reality, and outline real-world implementation challenges and potential solutions. RESULTS: Recent evidence shows that blended care approaches are clinically effective and improve service efficiency. Youth-specific technologies such as moderated online social therapy (MOST) are achieving a range of positive clinical and functional outcomes, while emerging technologies like virtual reality have strong evidence in anxiety disorder, and accumulating evidence in psychotic conditions. Implementation science frameworks show promise in helping overcome the common challenges faced in real-world adoption and ongoing use. CONCLUSION: The integrated, blended use of digital mental health technologies with face-to-face clinical care has the potential to improve care quality for young people while helping overcome the growing challenges faced by youth mental health service providers.

An open trial of the Things You Do Questionnaire: Changes in daily actions during internet-delivered treatment for depressive and anxiety symptoms.

Many psychological treatments aim to reduce symptoms of depression and anxiety by modifying maladaptive patterns of cognitions, behavior, and other actions. The Things You Do Questionnaire (TYDQ) was developed to measure the frequency of actions that are associated with psychological health in a reliable and valid manner. The present study examined treatment-related change in the frequency of actions measured by the TYDQ. Using an uncontrolled single-group design, 409 participants with self-reported symptoms of depression, anxiety, or both received access to an 8-week internet-delivered treatment course based on cognitive behavior therapy. Most (77 %) participants completed the treatment, completed questionnaires at post-treatment (83 %), and obtained significant reductions in symptoms of depression (d = 0.88) and anxiety at post-treatment (d = 0.97), as well as improvement in a measure of satisfaction with life (d = 0.36). Factor analyses supported the five-factor structure of the TYDQ, including Realistic Thinking, Meaningful Activities, Goals and Plans, Healthy Habits, and Social Connections. Those participants who, on average, engaged in the identified actions on the TYDQ at least half the days of the week reported lower symptoms of depression and anxiety at post-treatment. The psychometric properties of both a longer 60-item (TYDQ-60) and shorter 21-item (TYDQ-21) version were acceptable. These findings provide further evidence that there are modifiable activities that are strongly associated with psychological health. Future studies will test the replicability to these results in in a broader range of samples, including those seeking psychological treatment.

Predictors of functional impairment at assessment and functional improvement after treatment at a national digital mental health service.

Mental disorders are associated with impairment to daily functioning, which affects both the individual and society. Despite this, most research on treatment outcome only report symptom change. Self-reported days out of role (DOR) is a simple measure of functional impairment used in many population studies. The current study sought to report on the degree of functional impairment measured by DOR in a clinical sample at assessment, the factors associated with this impairment, the predictors of functional improvement after treatment and the relationship between symptomatic and functional change. Using a prospective uncontrolled observational cohort study design with a sample of 17,813 patients accessing a digital mental health service (DMHS), we examined self-reported demographic, psychosocial and clinical data. Using a series of univariate regression models and multivariate classification algorithms, we found that baseline DOR was associated with age, employment and relationship status, symptom severity, symptom chronicity and with the presence of several psychosocial difficulties. Baseline DOR was best predicted by older age, disability payments, higher symptom severity and increasing number of endorsed psychosocial difficulties (R2 = 32.7 %). Forty-one per cent of the sample experienced a >50 % or greater reduction in DOR following treatment. Those who were separated, unemployed or on disability payments, or with severe and chronic depression, experienced the greatest reductions in DOR after treatment. Changes in functioning were independent of changes in symptoms, highlighting the importance of functional impairment as a treatment outcome. This study found that many of the patients who access DMHS have significant levels of functional impairment, a large proportion obtain functional improvement after treatment, and improvement in function after treatment was independent of improvement in symptoms.

Vaccines against SARS-CoV-2 are safe to administer in patients with antibodies to pegaspargase.

OBJECTIVE: Allergic reactions to pegaspargase during ALL therapy are typically due to antibodies against polyethylene glycol (PEG), which is also used as a stabilizing agent in mRNA-based SARS-CoV-2 vaccines. To evaluate the safety of these vaccines in patients with anti-pegaspargase antibodies. METHODS: We retrospectively reviewed the records of patients treated for ALL who had received SARS-CoV-2 vaccinations. All patients had antibodies against pegaspargase assayed during ALL therapy prospectively and in response to clinical allergies. Symptoms of intolerance to vaccination were gathered retrospectively from chart abstraction. RESULTS: SARS-CoV-2 vaccination was well tolerated in all 78 patients with prior exposure to pegaspargase as part of their leukemia therapy. No reactions were observed in the 54 patients without a history of anti-pegaspargase antibodies or in 19 patients with antibodies who received mRNA vaccination. 1 patient who received the polysorbate containing Janssen vaccine experienced mild symptoms after vaccination not meeting the criteria of clinical allergy which spontaneously resolved within 25 minutes. CONCLUSION: SARS-CoV-2 vaccination is safe in this population.

The timing and magnitude of symptom improvements during an Internet-delivered transdiagnostic treatment program for anxiety and depression.

OBJECTIVE: In face-to-face treatments, mental health symptoms improve rapidly across the first few treatment sessions, and the pace of improvement slows with additional sessions. Some individuals also report clinically meaningful symptom improvements after only two or three treatment sessions. As the rate of symptom change has been given limited attention within digital treatments, the present study investigated the timing and magnitude of symptom change during an 8-week online treatment for anxiety and depression. METHOD: Three adult samples were derived from previous randomized controlled trials: generalized anxiety disorder (n = 165), major depression (n = 149), and mixed anxiety/depression (n = 262). Symptom scores were compared between consecutive weeks of treatment, and we examined the proportion of individuals who achieved a ≥ 25% or ≥ 50% improvement in symptoms each week. RESULTS: Across all three samples, symptoms improved more rapidly during the first half of treatment compared to the second half of treatment. Within the first 4 weeks, over half of the participants had experienced a ≥ 25% improvement in symptoms, and approximately a third of participants had experienced a ≥ 50% improvement in symptoms. This pattern of change was found irrespective of diagnostic status or outcome measure. CONCLUSIONS: A substantial number of people who receive internet-delivered treatments appear to experience rapid, large, and clinically significant symptom improvement early in treatment. These findings add to our theoretical understanding of symptom improvements during psychotherapy, and further research investigating the mechanisms of such change will inform the development of more effective treatments. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Clinical staging and the differential risks for clinical and functional outcomes in young people presenting for youth mental health care.

BACKGROUND: Clinical staging proposes that youth-onset mental disorders develop progressively, and that active treatment of earlier stages should prevent progression to more severe disorders. This retrospective cohort study examined the longitudinal relationships between clinical stages and multiple clinical and functional outcomes within the first 12 months of care. METHODS: Demographic and clinical information of 2901 young people who accessed mental health care at age 12-25 years was collected at predetermined timepoints (baseline, 3 months, 6 months, 12 months). Initial clinical stage was used to define three fixed groups for analyses (stage 1a: 'non-specific anxious or depressive symptoms', 1b: 'attenuated mood or psychotic syndromes', 2+: 'full-threshold mood or psychotic syndromes'). Logistic regression models, which controlled for age and follow-up time, were used to compare clinical and functional outcomes (role and social function, suicidal ideation, alcohol and substance misuse, physical health comorbidity, circadian disturbances) between staging groups within the initial 12 months of care. RESULTS: Of the entire cohort, 2093 young people aged 12-25 years were followed up at least once over the first 12 months of care, with 60.4% female and a baseline mean age of 18.16 years. Longitudinally, young people at stage 2+ were more likely to develop circadian disturbances (odds ratio [OR]=2.58; CI 1.60-4.17), compared with individuals at stage 1b. Additionally, stage 1b individuals were more likely to become disengaged from education/employment (OR=2.11, CI 1.36-3.28), develop suicidal ideations (OR=1.92; CI 1.30-2.84) and circadian disturbances (OR=1.94, CI 1.31-2.86), compared to stage 1a. By contrast, we found no relationship between clinical stage and the emergence of alcohol or substance misuse and physical comorbidity. CONCLUSIONS: The differential rates of emergence of poor clinical and functional outcomes between early versus late clinical stages support the clinical staging model's assumptions about illness trajectories for mood and psychotic syndromes. The greater risk of progression to poor outcomes in those who present with more severe syndromes may be used to guide specific intervention packages.