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ImportanceClinical trials have not established the optimal type, sequence, and duration of interventions for people at ultrahigh risk of psychosis.ObjectiveTo determine the effectiveness of a sequential and adaptive intervention strategy for individuals at ultrahigh risk of psychosis.Design, setting, and participantsThe Staged Treatment in Early Psychosis (STEP) sequential multiple assignment randomized trial took place within the clinical program at Orygen, Melbourne, Australia. Individuals aged 12 to 25 years who were seeking treatment and met criteria for ultrahigh risk of psychosis according to the Comprehensive Assessment of At-Risk Mental States were recruited between April 2016 and January 2019. Of 1343 individuals considered, 342 were recruited.InterventionsStep 1: 6 weeks of support and problem solving (SPS); step 2: 20 weeks of cognitive-behavioral case management (CBCM) vs SPS; and step 3: 26 weeks of CBCM with fluoxetine vs CBCM with placebo with an embedded fast-fail option of ω-3 fatty acids or low-dose antipsychotic medication. Individuals who did not remit progressed through these steps; those who remitted received SPS or monitoring for up to 12 months.Main outcomes and measuresGlobal Functioning: Social and Role scales (primary outcome), Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Montgomery-Åsberg Depression Rating Scale, quality of life, transition to psychosis, and remission and relapse rates.ResultsThe sample comprised 342 participants (198 female; mean [SD] age, 17.7 [3.1] years). Remission rates, reflecting sustained symptomatic and functional improvement, were 8.5%, 10.3%, and 11.4% at steps 1, 2, and 3, respectively. A total of 27.2% met remission criteria at any step. Relapse rates among those who remitted did not significantly differ between SPS and monitoring (step 1: 65.1% vs 58.3%; step 2: 37.7% vs 47.5%). There was no significant difference in functioning, symptoms, and transition rates between SPS and CBCM and between CBCM with fluoxetine and CBCM with placebo. Twelve-month transition rates to psychosis were 13.5% (entire sample), 3.3% (those who ever remitted), and 17.4% (those with no remission).Conclusions and relevanceIn this sequential multiple assignment randomized trial, transition rates to psychosis were moderate, and remission rates were lower than expected, partly reflecting the ambitious criteria set and challenges with real-world treatment fidelity and adherence. While all groups showed mild to moderate functional and symptomatic improvement, this was typically short of remission. While further adaptive trials that address these challenges are needed, findings confirm substantial and sustained morbidity and reveal relatively poor responsiveness to existing treatments.Trial registrationClinicalTrials.gov Identifier: NCT02751632.

ImportanceCerebral palsy (CP) is the most common childhood physical disability. Early intervention for children younger than 2 years with or at risk of CP is critical. Now that an evidence-based guideline for early accurate diagnosis of CP exists, there is a need to summarize effective, CP-specific early intervention and conduct new trials that harness plasticity to improve function and increase participation. Our recommendations apply primarily to children at high risk of CP or with a diagnosis of CP, aged 0 to 2 years.ObjectiveTo systematically review the best available evidence about CP-specific early interventions across 9 domains promoting motor function, cognitive skills, communication, eating and drinking, vision, sleep, managing muscle tone, musculoskeletal health, and parental support.Evidence reviewThe literature was systematically searched for the best available evidence for intervention for children aged 0 to 2 years at high risk of or with CP. Databases included CINAHL, Cochrane, Embase, MEDLINE, PsycInfo, and Scopus. Systematic reviews and randomized clinical trials (RCTs) were appraised by A Measurement Tool to Assess Systematic Reviews (AMSTAR) or Cochrane Risk of Bias tools. Recommendations were formed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and reported according to the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument.FindingsSixteen systematic reviews and 27 RCTs met inclusion criteria. Quality varied. Three best-practice principles were supported for the 9 domains: (1) immediate referral for intervention after a diagnosis of high risk of CP, (2) building parental capacity for attachment, and (3) parental goal-setting at the commencement of intervention. Twenty-eight recommendations (24 for and 4 against) specific to the 9 domains are supported with key evidence: motor function (4 recommendations), cognitive skills (2), communication (7), eating and drinking (2), vision (4), sleep (7), tone (1), musculoskeletal health (2), and parent support (5).Conclusions and relevanceWhen a child meets the criteria of high risk of CP, intervention should start as soon as possible. Parents want an early diagnosis and treatment and support implementation as soon as possible. Early intervention builds on a critical developmental time for plasticity of developing systems. Referrals for intervention across the 9 domains should be specific as per recommendations in this guideline.

To explore the characteristics and associated factors of oromotor dysfunction in minimally verbal children with cerebral palsy (CP) aged five to six years, recruited from a population-based registry. Twenty children with CP who were minimally verbal completed a standardised, observational oromotor assessment. Linear regression analyses examined the relationship between oromotor dysfunction and potential associated factors (e.g., fine and gross motor function, communication, and feeding). Oromotor dysfunction affected every participant and was identified in all structures examined (i.e., face, jaw, lips, and tongue). Oromotor movements showed little dissociation among jaw, lip, and tongue movements. Oromotor dysfunction was univariately associated with the Manual Ability Classification System levels IV–V (p = 0.001), reduced communication skills (p = 0.002), and a prolonged eating duration (>45 min) (p = 0.006), even when non-verbal cognition served as a covariate. Oromotor dysfunction was highly prevalent in our sample of minimally verbal children with CP, having significant functional impacts on feeding and communication. Findings suggest that fine motor function (i.e., Manual Ability Classification System levels IV–V) is a stronger predictor than gross motor function for identifying children with CP who are minimally verbal and at risk of oromotor dysfunction. Oromotor dysfunction was highly prevalent in our sample of minimally verbal children with cerebral palsy. Severe fine motor impairment strongly predicted oromotor dysfunction, indicating that fine motor function may provide an early indicator of impaired oromotor function for this clinical population. Robust, standardised measures of motor speech-related oromotor development suitable for children with cerebral palsy who are minimally verbal are lacking. Until such a measure is developed, formal evaluation may be achieved via oral motor assessments standardised for typically developing children, with the caveat one must interpret the results with caution. [ABSTRACT FROM AUTHOR]

Aim: To compare language, speech, and voice of children born preterm and at term, and determine relevant predictors of outcome.Method: Three hundred infants (150 males, 150 females; 149 born at <30wks' gestation, 151 term-born) were prospectively recruited at birth from the Royal Women's Hospital. We administered the Preschool Language Scales, Fifth Edition, Diagnostic Evaluation of Articulation and Phonology, Grade Roughness Breathiness Asthenia Strain Scale, and Pediatric Voice Handicap Index at 3 years, and compared groups. We examined hypothesized predictors in children born preterm: gestational age at birth, birthweight, sex, chronic lung disease, high social risk, multilingualism, neurodevelopmental diagnosis, and oromotor feeding.Results: Children born preterm had poorer language than children born at term (coefficient -5.43). Speech and voice were similar between groups (coefficients -0.70 to 1.63). Chronic lung disease predicted voice (coefficient 6.05); male sex (coefficients 4.54-6.18), high social risk (coefficient -6.02 to -9.30), and neurodevelopmental diagnosis (coefficients -16.42 to -20.61) predicted language.Interpretation: Children born before 30 weeks' gestation had poorer language than children born at term. Children born preterm with neurodevelopmental disabilities or high social risk experience poorer language outcomes, and would benefit from enrichment of their language environment.What This Paper Adds: Speech and voice outcomes were similar between children born preterm and at term. Male sex, high social risk, and neurodevelopmental diagnosis predicted language outcomes. [ABSTRACT FROM AUTHOR]

Competing Interests: Declaration of interests PDM is a founding director, patron, and former founding board member of headspace. He is the executive director of Orygen, Australia's National Centre of Excellence in Youth Mental Health and lead agency for five headspace centres across northwest Melbourne. He is a past President of the International Association for Youth Mental Health, and a past President of the IEPA; Early Intervention in Mental Health and of the Schizophrenia International Research Society. S-JB has provided paid expert witness work for UK charities and legal organisations. She is the author of two books related to the brain, education, and learning, for which she receives royalties. She gives talks in schools in the state and private sector, at education conferences, for education organisations, and for other public, private, and third sector organisations (some talks are remunerated). She is a member of the Rethinking Assessment group, the Steering Committee of the Cambridge Centre of Science Policy, the Technical Advisory Group for the UK Government Department of Education's Education and Outcomes Panel-C Study, the Singapore Government National Research Foundation Scientific Advisory Board, and the Singapore Government Human Potential Scientific Advisory Board. She was a member of the Times Education Commission (2021–22). IBH has received honoraria for consultancy and educational activities from Janssen Cilag. He was a member of the Clinical Advisory Group for the evaluation of the Better Access to Psychiatrists, Psychologists and General Practitioners through the Medicare Benefits Schedule initiative, and is a member of Mental Health Reform Advisory Committee (Department of Health). He is the Chief Scientific Advisor to and a 3·2% equity shareholder in InnoWell, which aims to transform mental health services through the use of innovative technologies. FAEA has received honoraria for consultancy from Grand Challenges Canada and is a past member of the World Economic Forum's Global Future Council on Mental Health. AMC is a director of headspace, Australia's National Youth Mental Health Foundation, and the National Education Alliance for Borderline Personality Disorder. AD is the Academic Secretary for the Royal College of Psychiatrists’ Faculty of Child and Adolescent Psychiatry, a research advisory group member of the UK National Society for the Prevention of Cruelty to Children, a member of the UK Trauma Council, and an evidence panel member of the Early Intervention Foundation. TF's research group receives funding for consultancy to Place2Be, a third sector organisation that provides mental health training, support, and interventions to schools across the UK. JH is executive director of Youth Wellness Hubs Ontario and receives funding from Graham Boeckh Foundation and other donors through the Centre for Addiction and Mental Health Foundation. AJ is a trustee of the Samaritans and MQ. She has received fees for lecturing from the Scottish Association of Mental Health. She is an advisory board member of Our Future Health, UK. FK-L's work is the subject of publishing contracts with multiple companies in the EU, Magellan, Cobalt Therapeutics in the USA, and the National Health Service in the UK. Although she has received no remuneration to date, she might receive royalties in the future. She is a non-executive director of Orygen. CK is the founder of Wida, a digital mental health platform. He has received consulting fees from the UN Children's Fund. He has received grants from MQ: Transforming Mental Health in the UK, the Royal Academy of Engineering in the UK, the National Institutes of Health in the USA, the Medical Research Council in the UK, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul in Brazil. DR is a Chief Scientific Advisor to headspace, Australia's National Youth Mental Health Foundation. JT receives book royalties from Simon and Schuster, legal consulting fees from Bergman and Little and the Attorney General's office of the State of Tennessee, and honoraria for speaking engagements. EK is the immediate past President of the IEPA: Early Intervention in Mental Health, and during the period of the Commission was the President elect and President. All other authors declare no competing interests.