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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.

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]

Mental Health First Aid (MHFA) is a potentially valuable first response in mental healthcare. MHFA is formulated as an extension of Psychological First Aid, the latter being a more focal response to crises and disasters. MHFA is a broader strategy which aims to improve the general public's immediate response to mental ill health and mental health crisis. While its effect on those trained in MHFA has been promising, recent meta-analyses have failed to detect any significant benefit to individuals who receive support from an MHFA trainee. Such outcomes highlight the need to revisit the content and implementation of MHFA to optimise and realise the full potential of the concept. Possible solutions are discussed, including developing new MHFA content using methodologies that foster innovation and creativity, in addition to improving the quality and effectiveness of MHFA training., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Within the embryonic early psychosis field in the early 1990s, the conceptualisation and definition of an at-risk or ultra-high-risk (UHR) mental state for psychosis was a breakthrough which transformed the clinical and research landscape in psychiatry. Twenty-five years later, we have a new evidence base that has illuminated the neurobiology of the onset phase of psychotic disorder, delivered Cochrane level 1 evidence showing that the onset of full-threshold sustained psychotic disorder can be at least delayed, and is paving the way to a new generation of transdiagnostic research. Here, we document the contribution of the UHR approach to understanding the underlying mechanisms of psychosis onset as well as the long-term outcomes. Particularly, we highlight that psychosis onset can be delayed in those meeting UHR criteria and that these criteria have a higher valence for subsequent psychotic disorders and some valence for persistent non-psychotic syndromes. Critiques have helped to identify some of the limitations of this paradigm, which are acknowledged. These include evidence that psychotic disorders can emerge more acutely and from other, as yet undefined, precursor states. Rather than defending, or alternatively questioning the value of, the UHR approach, we propose a broader, transdiagnostic staging model that is consistent with the pluripotent and variably comorbid trajectories for mental disorders. This approach moves beyond psychosis to capture a wider range of subthreshold symptoms and full-threshold disorders, thus enhancing prediction for the emergence and progression of a range of mental disorders, as well as providing new avenues for early intervention and prevention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Early intervention is a fundamental principle in health care and the past two decades have seen it belatedly introduced into the field of mental health. This began in psychotic disorders, arguably the least promising place to start. The steady accumulation of scientific evidence for early intervention has eventually overwhelmed the sceptics, transformed thinking in psychotic disorders and created an international wave of service reform. This paradigm shift has paved the way to a more substantial one: early intervention across the full diagnostic spectrum. 75% of mental illnesses emerge before the age of 25 years, and young people bear the major burden for those disorders that threaten the many decades of productive adult life. The paradox is that young people aged between 12 and 25 years have had by far the worst levels of access to mental health care across the whole lifespan. Health services are poorly designed, grossly under-resourced and typically unfriendly to, and untrusted by, young people. Furthermore, until recently there has been a quite striking lack of interest in this transitional age group from clinicians and researchers alike, who had unthinkingly accepted the paediatric-adult split of mainstream medicine without questioning its utility and validity for our field and our young patients. Over the past decade, however, a major shift in momentum has occurred to take early intervention in youth mental health more seriously. Here we discuss the recent advances and evidence supporting an innovative integrated model of youth mental health care and look to the future., Competing Interests: Competing interests: PDM is a Director of headspace., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)