Electrodiagnostic findings in patients with non-COVID-19- and COVID-19-related acute respiratory distress syndrome.

BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) is a frequent neurological manifestation in patients with acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19) infection. CIPNM diagnosis is usually limited to clinical evaluation. We compared patients with ARDS from COVID-19 and other aetiologies, in whom a neurophysiological evaluation for the detection of CIPNM was performed. The aim was to determine if there were any differences between these two groups in frequency of CINPM and outcome at discharge from the intensive care unit (ICU). MATERIALS AND METHODS: This was a single-centre retrospective study performed on mechanically ventilated patients consecutively admitted (January 2016-June 2020) to the ICU of Careggi Hospital, Florence, Italy, with ARDS of different aetiologies. Neurophysiological evaluation was performed on patients with stable ventilation parameters, but marked widespread hyposthenia (Medical Research Council score <48). Creatine phosphokinase (CPK), lactic dehydrogenase (LDH) and mean morning glycaemic values were collected. RESULTS: From a total of 148 patients, 23 with COVID-19 infection and 21 with ARDS due to other aetiologies, underwent electroneurography/electromyography (ENG/EMG) recording. Incidence of CIPNM was similar in the two groups, 65% (15 of 23) in COVID-19 patients and 71% (15 of 21) in patients affected by ARDS of other aetiologies. At ICU discharge, subjects with CIPNM more frequently required ventilatory support, regardless the aetiology of ARDS. CONCLUSION: ENG/EMG represents a useful tool in the identification of the neuromuscular causes underlying ventilator wean failure and patient stratification. A high incidence of CIPNM, with a similar percentage, has been observed in ARDS patients of all aetiologies.

Severe speech impairment is a distinguishing feature of FOXP1-related disorder.

AIM: To delineate the speech and language phenotype of a cohort of individuals with FOXP1-related disorder. METHOD: We administered a standardized test battery to examine speech and oral motor function, receptive and expressive language, non-verbal cognition, and adaptive behaviour. Clinical history and cognitive assessments were analysed together with speech and language findings. RESULTS: Twenty-nine patients (17 females, 12 males; mean age 9y 6mo; median age 8y [range 2y 7mo-33y]; SD 6y 5mo) with pathogenic FOXP1 variants (14 truncating, three missense, three splice site, one in-frame deletion, eight cytogenic deletions; 28 out of 29 were de novo variants) were studied. All had atypical speech, with 21 being verbal and eight minimally verbal. All verbal patients had dysarthric and apraxic features, with phonological deficits in most (14 out of 16). Language scores were low overall. In the 21 individuals who carried truncating or splice site variants and small deletions, expressive abilities were relatively preserved compared with comprehension. INTERPRETATION: FOXP1-related disorder is characterized by a complex speech and language phenotype with prominent dysarthria, broader motor planning and programming deficits, and linguistic-based phonological errors. Diagnosis of the speech phenotype associated with FOXP1-related dysfunction will inform early targeted therapy. What this paper adds Individuals with FOXP1-related disorder have a complex speech and language phenotype. Dysarthria, which impairs intelligibility, is the dominant feature of the speech profile. No participants were receiving speech therapy for dysarthria, but were good candidates for therapy Features of speech apraxia occur alongside persistent phonological errors. Language abilities are low overall; however, expressive language is a relative strength.

Speech in children with cerebral palsy.

AIM: To examine the frequency, characteristics, and factors associated with speech delay and disorder in a community sample of children with cerebral palsy (CP). METHOD: Participants were 84 children (37 females, 47 males; aged between 4y 11mo-6y 6mo) with CP identified through a population-based registry. Speech and oromotor function were systematically evaluated to provide a differential diagnosis of articulation, phonological, and motor speech disorders. RESULTS: In total, 82% (69/84) of participants had delayed or disordered speech production, including minimally verbal presentations (n=20). Verbal participants (n=64) presented with dysarthria (78%), articulation delay or disorder (54%), phonological delay or disorder (43%), features of childhood apraxia of speech (CAS) (17%), or mixed presentations across these conditions. Speech intelligibility was poorest in those with dysarthria and features of CAS. Speech delay or disorder in verbal participants was associated with language impairment (p=0.002) and reduced health-related quality of life (p=0.04) (Fisher's exact test). Poorer speech accuracy (i.e. lower percentage consonants correct) correlated with greater impairments in both language (p<0.001) and oromotor function (p<0.001) (Spearman's test). INTERPRETATION: The speech profile of children with CP is characterized by impairment at multiple levels of speech production (phonetic, cognitive-linguistic, neuromuscular execution, and high-level planning/programming), highlighting the importance of a personalized differential diagnosis informing targeted treatment.

Communication in children born very preterm: a prospective cohort study.

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.

Communication behaviours of children with cerebral palsy who are minimally verbal.

BACKGROUND: There is a lack of population-based studies exploring the communicative behaviours of minimally verbal children with cerebral palsy (CP), with factors associated with superior and poorer communication outcomes unknown. This study aimed to examine the communication behaviours of minimally verbal children with CP recruited from a representative community sample and to identify factors associated with communication outcomes. METHODS: Twenty minimally verbal children aged 5-6 years, recruited through the Victorian Cerebral Palsy Register, completed the Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS-DP). Linear regressions examined child-related and environmental factors associated with communication outcomes. RESULTS: CSBS-DP total raw scores ranged from 0 to 113. Strengths were the use of conventional gestures and understanding of language. Challenges were noted in using sequential action schemes during play. Communication typically served to regulate the behaviour of others. All participants demonstrated reduced functional communication (Communication Function Classification System levels III-IV). In the multivariable regression model adjusted for cognition, poorer communication skills were associated with Manual Ability Classification System levels IV-V (P = 0.004). CONCLUSIONS: Although some children with CP who are minimally verbal use a variety of communication functions, significant functional limitations may be apparent. Severe upper limb impairment may provide an early indication of greater communication difficulties.

Why do psychiatrists doubt the value of early intervention? The power of illusion.

OBJECTIVE: Face validity and the best available evidence strongly support the value of early intervention (EI) for psychotic disorders, and increasingly for other mental illnesses. Yet its value continues to be intensely criticised by some academics and doubted by many psychiatrists. This disconnect is examined through the lens of the 'clinician's illusion'. CONCLUSIONS: A number of sources fuel resistance to EI; however, the cumulative exposure to persistent and disabling illness that dominates the day-to-day experience of psychiatrists may be a key influence. This experience forms the basis of the clinician's illusion, a hidden bias health professionals develop as a natural consequence of their clinical experiences, which shapes belief and perception of prognosis, and breeds therapeutic nihilism. This bias has been reinforced by grossly under-resourced systems of mental health care, undermining morale and adding a sense of learned helplessness to our mindset.

Evidence- and Consensus-Based Guidelines for the Management of Communication and Swallowing Disorders Following Pediatric Traumatic Brain Injury.

OBJECTIVE: Evidence-based management guidelines for communication and swallowing disorders following pediatric traumatic brain injury (TBI) are scarcely available, potentially resulting in suboptimal outcomes. To improve clinical care of this population, a multidisciplinary guideline development committee was formed to develop evidence-based recommendation (EBR) and consensus-based recommendation (CBR) for the management of speech, language, and swallowing disorders during the first year of recovery. METHODS: A 3-round Delphi survey was completed by the committee to reach agreement (80% consensus) for the CBRs. Systematic review evidence guided development of EBRs, devised using the National Health and Medical Research Council statement form. RESULTS: Altogether, 30 recommendations (5 EBRs and 25 CBRs) were developed to guide management of speech, language, and swallowing disorders, including prediction of these disorders; health team required, optimal timing of assessment; assessment tools; intervention strategies and commencement of treatment; and key information to support parents. CONCLUSION: The developed recommendations provide a basis for the systematic management of communication and swallowing disorders to be refined as new evidence emerges. Key recommendations include screening of children with moderate/severe TBI for these disorders acutely using specified measures. Patients with severe TBI and prolonged ventilation are a particular at-risk group and should be considered for early referral to speech-language pathology to support timely diagnosis and management. No evidence was identified to support an EBR for treatment, highlighting a key area for research.

Who to Refer for Speech Therapy at 4 Years of Age Versus Who to "Watch and Wait"?

OBJECTIVE: To examine predictors of speech disorder resolution versus persistence at age 7 years in children with speech errors at age 4 years. STUDY DESIGN: Participants were drawn from a longitudinal, community cohort. Assessment at age 4 years (N?=?1494) identified children with speech errors. Reassessment at age 7 years allowed categorization into resolved or persistent categories. Logistic regression examined predictors of speech outcome, including family history, sex, socioeconomic status, nonverbal intelligence, and speech error type (delay vs disorder). RESULTS: At age 7 years, persistent errors were seen in over 40% of children who had errors at age 4 years. Speech symptomatology was the only significant predictor of outcome (P?=?.02). Children with disordered errors at age 4 years were twice as likely to have poor speech outcomes at age 7 years compared with those with delayed errors. CONCLUSIONS: Children with speech delay at age 4 years seem more likely to resolve, and this might justify a "watch and wait" approach. In contrast, those with speech disorder at age 4 years appear to be at greater risk for persistent difficulties, and could be prioritized for therapy to offset long-term impacts.

Language outcomes of children with cerebral palsy aged 5 years and 6 years: a population-based study.

AIM: To examine the frequency, range, and features of language impairment in a community sample of children with cerebral palsy (CP) aged 5 to 6 years. METHOD: Children with CP born between 2005 and 2007 were identified through the Victorian Cerebral Palsy Register. Eighty-four participants were recruited, representing 48% of the contacted families. The recruited sample was representative of non-participants. Participants completed standardized measures of receptive and expressive language, and non-verbal cognition. RESULTS: Language impairment was identified in 61% (51/84) of participants. Twenty-four per cent (20/84) were non-verbal. Co-occurring receptive and expressive language impairment was common (37/84, 44%). Isolated receptive (6/84, 7%) and expressive (4/84, 5%) impairments occurred relatively infrequently. At a group level, verbal and non-verbal participants demonstrated deficits across language subdomains (i.e. semantics, syntax, morphology), rather than in single domains. Cognitive impairment and Gross Motor Function Classification System levels IV and V were associated with higher rates of language impairment (odds ratio [OR] 15.2, 95% confidence interval [CI] 3.2-71.8 and OR 8.5, 95% CI 1.8-40.3 respectively). Only cognition was independently associated with language impairment when both of these factors were considered within a multivariable model. INTERPRETATION: Language impairment was common in 5-year-old and 6-year-old children with CP, affecting three out of five children. Participants were impaired across linguistic subdomains indicating a generalized language deficit. Findings suggest most children would benefit from a clinical language assessment. To target services effectively, subgroups of individuals with CP at greatest risk for language impairment need to be identified.

Speech and language in a genotyped cohort of individuals with Kabuki syndrome.

Speech and language deficits are commonly associated with Kabuki syndrome. Yet little is known regarding the specific symptomatology of these disorders, preventing use of targeted treatment programs. Here we detail speech and language in 16 individuals with Kabuki syndrome (thirteen with KMT2D mutations, one with a KDM6A mutation, and two mutation-negative cases), aged 4-21 years. The most striking speech deficit was dysarthria, characterised by imprecise consonants, harsh vocal quality, hypernasality, reduced rate and stress, and distorted pitch. Oromotor functioning was also impaired. Delayed, rather than disordered, articulation and phonology was common. Both receptive and expressive language abilities were reduced in the majority and deficits were noted across all language sub-domains (i.e., semantics, syntax, morphology, and pragmatics) with no clear differentiation or specific language profile. Individuals with Kabuki syndrome present with a heterogenous pattern of oromotor, speech, and language deficits. This variability fits with the multisystem nature of the disorder, which may encompass neurological, orofacial structural, hearing, and cognitive deficits, any or all of which may contribute to speech or language impairment. Our results suggest that all individuals with Kabuki syndrome have some level of communication deficit, warranting speech pathology involvement in all cases.

Erythrocyte membrane fatty acid concentrations and myelin integrity in young people at ultra-high risk of psychosis.

Decreased white matter (WM) integrity and disturbance in fatty acid composition have been reported in individuals at ultra-high risk of psychosis (UHR). The current study is the first to investigate both WM integrity and erythrocyte membrane polyunsaturated fatty acid (PUFA) levels as potential risk biomarkers for persistent UHR status, and global functioning in UHR individuals. Forty UHR individuals were analysed at baseline for erythrocyte membrane PUFA concentrates. Tract-based spatial statistics (TBSS) was used to analyse fractional anisotropy (FA) and diffusivity measures. Measures of global functioning and psychiatric symptoms were evaluated at baseline and at 12-months. Fatty acids and WM indices did not predict functional outcomes at baseline or 12-months. Significant differences were found in FA between UHR remitters and non-remitters (individuals who no longer met UHR criteria versus those who continued to meet criteria at 12-months). Docosahexaenoic acid (DHA) was found to be a significant predictor of UHR status at 12-months, as was the interaction between the sum of ώ-3 and whole brain FA, and the interaction between the right anterior limb of the internal capsule and the sum of ώ-3. The results confirm that certain fatty acids have a unique relationship with WM integrity in UHR individuals.

A Sequential Adaptive Intervention Strategy Targeting Remission and Functional Recovery in Young People at Ultrahigh Risk of Psychosis: The Staged Treatment in Early Psychosis (STEP) Sequential Multiple Assignment Randomized Trial.

Importance: Clinical trials have not established the optimal type, sequence, and duration of interventions for people at ultrahigh risk of psychosis. Objective: To determine the effectiveness of a sequential and adaptive intervention strategy for individuals at ultrahigh risk of psychosis. Design, Setting, and Participants: The 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. Interventions: Step 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 Measures: Global 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. Results: The 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 Relevance: In 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 Registration: ClinicalTrials.gov Identifier: NCT02751632.

Designing and scaling up integrated youth mental health care.

Mental ill-health represents the main threat to the health, survival and future potential of young people around the world. There are indications that this is a rising tide of vulnerability and need for care, a trend that has been augmented by the COVID-19 pandemic. It represents a global public health crisis, which not only demands a deep and sophisticated understanding of possible targets for prevention, but also urgent reform and investment in the provision of developmentally appropriate clinical care. Despite having the greatest level of need, and potential to benefit, adolescents and emerging adults have the worst access to timely and quality mental health care. How is this global crisis to be addressed? Since the start of the century, a range of co-designed youth mental health strategies and innovations have emerged. These range from digital platforms, through to new models of primary care to new services for potentially severe mental illness, which must be locally adapted according to the availability of resources, workforce, cultural factors and health financing patterns. The fulcrum of this progress is the advent of broad-spectrum, integrated primary youth mental health care services. They represent a blueprint and beach-head for an overdue global system reform. While resources will vary across settings, the mental health needs of young people are largely universal, and underpin a set of fundamental principles and design features. These include establishing an accessible, "soft entry" youth primary care platform with digital support, where young people are valued and essential partners in the design, operation, management and evaluation of the service. Global progress achieved to date in implementing integrated youth mental health care has highlighted that these services are being accessed by young people with genuine and substantial mental health needs, that they are benefiting from them, and that both these young people and their families are highly satisfied with the services they receive. However, we are still at base camp and these primary care platforms need to be scaled up across the globe, complemented by prevention, digital platforms and, crucially, more specialized care for complex and persistent conditions, aligned to this transitional age range (from approximately 12 to 25 years). The rising tide of mental ill-health in young people globally demands that this focus be elevated to a top priority in global health.

Oromotor dysfunction in minimally verbal children with cerebral palsy: characteristics and associated factors.

AIM: 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. METHODS: 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). RESULTS: 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. INTERPRETATION: 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. IMPLICATIONS FOR REHABILITATIONOromotor 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.

Incidence of mutism, dysarthria and dysphagia associated with childhood posterior fossa tumour.

PURPOSE: Dysarthria and dysphagia are known complications following posterior fossa tumour (PFT) surgery. Outcome studies for these disorders, however, have focused on a select sub-group of children with mutism. Little is known regarding the incidence or features of these impairments in a consecutively admitted sample of children with PFT. This study describes the incidence and features of mutism, dysarthria and dysphagia during the acute post-surgical phase in a consecutive sample of children with PFT, unselected for the presence of mutism. METHODS: A retrospective medical chart review of children aged 2 to 18 years consecutively admitted with PFT between January 2003 and January 2008 was conducted. RESULTS: Twenty-seven children with PFT were identified. Post-surgical mutism, dysarthria and dysphagia were recorded in 9/27 (33%), 8/27 (30%) and 9/27 (33%) cases, respectively. Dysarthria most commonly involved deficits in articulation; however, impairments in respiration, phonation and prosody were also reported. Dysphagia involved all stages of swallowing (i.e., pre-oral anticipatory, oral preparatory, oral and pharyngeal). Eighty-nine percent of children (8/9) presented with dysphagia at hospital discharge. CONCLUSIONS: The incidence of acute presentation of mutism, dysarthria and dysphagia post-surgery was relatively high, affecting around one in three cases. This incidence rate, considered together with the fact that over half of all cases had co-morbid communication or swallowing impairments, suggests that health professionals should be aware of the likelihood of dysarthria and dysphagia presentation in the acute period and consider speech pathology referral where necessary.

Intervention strategies for ultra-high risk for psychosis: Progress in delaying the onset and reducing the impact of first-episode psychosis.

Over a quarter of a century ago, the formulation of the "at risk mental state" and operational criteria to prospectively identify individuals at "clinical" or "ultra-high risk" (UHR) for psychosis created a global wave of research momentum aimed at predicting and preventing first-episode psychosis. A substantial number of randomized controlled trials (RCTs) were conducted to determine if transition to psychosis could be delayed or even prevented. The efficacy of a range of interventions was examined, with standard meta-analyses clearly indicating that these could at least delay transition for 1-2 years and that outcomes improve. Recently, network meta-analyses have attempted to identify the most effective intervention. These highlighted the fact that no one form of intervention is superior to the rest, a finding interpreted in such a way as to create doubts concerning the value of intervening. These doubts have been reinforced by a subsequent Cochrane review which judged the quality of the evidence as low or very low. Here, we report a narrative review of findings from RCTs and meta-analyses on the efficacy of interventions in UHR. We also critique the network meta-analyses and the Cochrane review, and indicate that many of the trials were of the highest possible quality for such research, and were published in top ranked psychiatry journals, which demand such quality. Although outcomes vary, and the UHR group is clearly heterogeneous, we highlight the clinical benefits of psychosocial treatment. The next generation of clinical trials seek to elucidate the optimal type, duration and sequence of interventions.

Comparison of Sympathetic Skin Response (SSR) between Electrical and Acoustic Stimuli in a Healthy Pediatric Population.

Data in the literature report that latency and morphology in the cutaneous sympathetic skin response (SSR) do not change according to the type of stimulus delivered, unlike the amplitude which shows greater values in relation to the intensity of the physical impact caused in patient. Since the acoustic stimulus represents a method better tolerated by the pediatric patient, the aim of this study is to evaluate the presence or absence of significant differences in SSR between electrical and acoustic stimuli. The SSR was performed for each child of 18 recruited in this study, deriving from the palm of the hand and the sole of the foot and initially delivering an electrical stimulus at the level of the median nerve at the wrist. Two acoustic stimuli were subsequently delivered with the aid of audiometric headphones. Our results show no significant differences for the amplitude values obtained (p values > 0.05). For the latency there was a statistically significant difference (p-value = 0.001) for the left hand, subsequently not confirmed by the comparison performed between the two sides (p-values = 0.28 and 0.56). If these preliminary data are confirmed by a larger sample, the acoustic stimulus could be introduced in a standardized protocol for performing SSR in pediatric patients.

Preventive interventions for individuals at ultra high risk for psychosis: An updated and extended meta-analysis.

Intervention at the earliest illness stage, in ultra or clinical high-risk individuals, or indicated prevention, currently represents the most promising strategy to ameliorate, delay or prevent psychosis. We review the current state of evidence and conduct a broad-spectrum meta-analysis of various outcomes: transition to psychosis, attenuated positive and negative psychotic symptoms, mania, depression, anxiety, general psychopathology, symptom-related distress, functioning, quality of life, and treatment acceptability. 26 randomized controlled trials were included. Meta-analytically pooled interventions reduced transition rate (risk ratio [RR] = 0.57, 95%CI 0.41-0.81) and attenuated positive psychotic symptoms at 12-months (standardized mean difference = -0.15, 95%CI = -0.28--0.01). When stratified by intervention type (pharmacological, psychological), only the pooled effect of psychological interventions on transition rate was significant. Cognitive behavioral therapy (CBT) was associated with a reduction in incidence at 12-months (RR = 0.52, 95%CI = 0.33-0.82) and 18-48-months (RR = 0.60, 95%CI = 0.42-0.84), but not 6-months. Findings at 12-months and 18-48-months were robust in sensitivity and subgroup analyses. All other outcomes were non-significant. To date, effects of trialed treatments are specific to transition and, a lesser extent, attenuated positive symptoms, highlighting the future need to target other symptom domains and functional outcomes. Sound evidence supports CBT in reducing transition and the value of intervening at this illness stage. STUDY REGISTRATION: Research Registry ID: reviewregistry907.

Early Intervention for Children Aged 0 to 2 Years With or at High Risk of Cerebral Palsy: International Clinical Practice Guideline Based on Systematic Reviews.

Importance: Cerebral 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. Objective: To 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 Review: The 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. Findings: Sixteen 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 Relevance: When 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.