What is the duration of untreated psychosis worldwide? - A meta-analysis of pooled mean and median time and regional trends and other correlates across 369 studies.

Duration of untreated psychosis (DUP) has been associated with poor mental health outcomes. We aimed to meta-analytically estimate the mean and median DUP worldwide, evaluating also the influence of several moderating factors. This PRISMA/MOOSE-compliant meta-analysis searched for non-overlapping individual studies from inception until 9/12/2022, reporting mean ± s.d. or median DUP in patients with first episode psychosis (FEP), without language restrictions. We conducted random-effect meta-analyses, stratified analyses, heterogeneity analyses, meta-regression analyses, and quality assessment (PROSPERO:CRD42020163640). From 12 461 citations, 369 studies were included. The mean DUP was 42.6 weeks (95% confidence interval (CI) 40.6-44.6, k = 283, n = 41 320), varying significantly across continents (p < 0.001). DUP was (in descending order) 70.0 weeks (95% CI 51.6-88.4, k = 11, n = 1508) in Africa; 48.8 weeks (95% CI 43.8-53.9, k = 73, n = 12 223) in Asia; 48.7 weeks (95% CI 43.0-54.4, k = 36, n = 5838) in North America; 38.6 weeks (95% CI 36.0-41.3, k = 145, n = 19 389) in Europe; 34.9 weeks (95% CI 23.0-46.9, k = 11, n = 1159) in South America and 28.0 weeks (95% CI 20.9-35.0, k = 6, n = 1203) in Australasia. There were differences depending on the income of countries: DUP was 48.4 weeks (95% CI 43.0-48.4, k = 58, n = 5635) in middle-low income countries and 41.2 weeks (95% CI 39.0-43.4, k = 222, n = 35 685) in high income countries. Longer DUP was significantly associated with older age (ß = 0.836, p < 0.001), older publication year (ß = 0.404, p = 0.038) and higher proportion of non-White FEP patients (ß = 0.232, p < 0.001). Median DUP was 14 weeks (Interquartile range = 8.8-28.0, k = 206, n = 37 215). In conclusion, DUP is high throughout the world, with marked variation. Efforts to identify and intervene sooner in patients with FEP, and to promote global mental health and access to early intervention services (EIS) are critical, especially in developing countries.

Associations between disturbed sleep and attenuated psychotic experiences in people at clinical high risk for psychosis.

BACKGROUND: Pre-diagnostic stages of psychotic illnesses, including 'clinical high risk' (CHR), are marked by sleep disturbances. These sleep disturbances appear to represent a key aspect in the etiology and maintenance of psychotic disorders. We aimed to examine the relationship between self-reported sleep dysfunction and attenuated psychotic symptoms (APS) on a day-to-day basis. METHODS: Seventy-six CHR young people completed the Experience Sampling Methodology (ESM) component of the European Union Gene-Environment Interaction Study, collected through PsyMate® devices, prompting sleep and symptom questionnaires 10 times daily for 6 days. Bayesian multilevel mixed linear regression analyses were performed on time-variant ESM data using the brms package in R. We investigated the day-to-day associations between sleep and psychotic experiences bidirectionally on an item level. Sleep items included sleep onset latency, fragmentation, and quality. Psychosis items assessed a range of perceptual, cognitive, and bizarre thought content common in the CHR population. RESULTS: Two of the seven psychosis variables were unidirectionally predicted by previous night's number of awakenings: every unit increase in number of nightly awakenings predicted a 0.27 and 0.28 unit increase in feeling unreal or paranoid the next day, respectively. No other sleep variables credibly predicted next-day psychotic symptoms or vice-versa. CONCLUSION: In this study, the relationship between sleep disturbance and APS appears specific to the item in question. However, some APS, including perceptual disturbances, had low levels of endorsement amongst this sample. Nonetheless, these results provide evidence for a unidirectional relationship between sleep and some APS in this population.

Age dependent effects of early intervention in borderline personality disorder in adolescents.

BACKGROUND: Psychological treatments for young people with sub-threshold or full-syndrome borderline personality disorder (BPD) are found to be effective. However, little is known about the age at which adolescents benefit from early intervention. This study investigated whether age affects the effectiveness of early intervention for BPD. METHODS: N = 626 participants (M age = 15 years, 82.7% female) were consecutively recruited from a specialized outpatient service for early intervention in BPD in adolescents aged 12- to 17-years old. DSM-IV BPD criteria were assessed at baseline, one-year (n = 339) and two-year (n = 279) follow-up. RESULTS: Older adolescents presented with more BPD criteria (χ2(1) = 58.23, p < 0.001) and showed a steeper decline of BPD criteria over the 2-year follow-up period compared with younger adolescents (χ2(2) = 13.53, p = 0.001). In an attempt to disentangle effects of early intervention from the natural course of BPD, a parametrized regression model was used. An exponential decrease (b = 0.10, p < 0.001) in BPD criteria was found when starting therapy over the 2-year follow-up. This deviation from the natural course was impacted by age at therapy commencement (b = 0.06, p < 0.001), although significant across all ages: older adolescents showed a clear decrease in BPD criteria, and young adolescents a smaller decrease. CONCLUSIONS: Early intervention appears effective across adolescence, but manifests differently: preventing the normative increase of BPD pathology expected in younger adolescents, and significantly decreasing BPD pathology in older adolescents. The question as to whether developmentally adapted therapeutic interventions could lead to an even increased benefit for younger adolescents, should be explored in future studies.

A randomised double-blind placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at risk Mental States: The NAYAB study.

BACKGROUND: Inflammatory mechanisms are thought to contribute to the onset of psychosis in persons with an at-risk mental state (ARMS). We investigated whether the anti-inflammatory properties of minocycline and omega-3 polyunsaturated fatty acids (omega-3), alone or synergistically, would prevent transition to psychosis in ARMS in a randomised, double-blind, placebo-controlled trial in Pakistan. METHODS: 10,173 help-seeking individuals aged 16-35 years were screened using the Prodromal Questionaire-16. Individuals scoring 6 and over were interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to confirm ARMS. Participants (n = 326) were randomised to minocycline, omega-3, combined minocycline and omega-3 or to double placebo for 6 months. The primary outcome was transition to psychosis at 12 months. FINDINGS: Forty-five (13.8 %) participants transitioned to psychosis. The risk of transition was greater in those randomised to omega-3 alone or in combination with minocycline (17.3.%), compared to 10.4 % in those not exposed to omega-3; a risk-ratio (RR) of 1.67, 95 % CI [0.95, 2.92] p = 0.07. The RR for transitions on minocycline vs. no minocycline was 0.86, 95 % CI [0.50, 1.49] p > 0.10. In participants who did not become psychotic, CAARMS and depression symptom scores were reduced at six and twelve months (mean CAARMS difference = 1.43; 95 % CI [0.33, 1.76] p < 0.01 in those exposed to omega-3. Minocycline did not affect CAARMS or depression scores. INTERPRETATION: In keeping with other studies, omega-3 appears to have beneficial effects on ARMS and mood symptom severity but it increased transition to psychosis, which may reflect metabolic or developmental consequences of chronic poor nutrition in the population. Transition to psychosis was too rare to reveal a preventative effect of minocycline but minocycline did not improve symptom severity. ARMS symptom severity and transition to psychosis appear to have distinct pathogeneses which are differentially modulated by omega-3 supplementation. FUNDING: The study was funded by the Stanley Research Medical Institute.

Plasma complement and coagulation proteins as prognostic factors of negative symptoms: An analysis of the NAPLS 2 and 3 studies.

INTRODUCTION: Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised. METHODS: In the North American Prodrome Longitudinal Studies 2 and 3, negative symptoms in 431 individuals at clinical high-risk for psychosis (mean age: 18.2, SD 3.6; 42.5 % female) were measured at multiple visits over 2 years using the Scale of Psychosis-Risk Symptoms. Plasma proteins were quantified at baseline using mass spectrometry. Four factors were derived to represent levels of proteins involved in the activation or regulation of the complement or coagulation systems. The relationships between standardised protein group factors and serial measurements of negative symptoms over time were modelled using generalised least squares regression. Analyses were adjusted for baseline candidate prognostic factors: negative symptoms, positive symptoms, functioning, depressive symptoms, suicidal ideation, cannabis use, tobacco use, antipsychotic use, antidepressant use, age, and sex. RESULTS: Clinical and demographic prognostic factors of follow-up negative symptoms included negative, positive, and depressive symptoms, functioning, and age. Adjusting for all candidate prognostic factors, the complement regulators group and the coagulation regulators group were identified as prognostic factors of follow-up negative symptoms (ß: 0.501, 95 % CI: 0.160, 0.842; ß: 0.430, 95 % CI: 0.080, 0.780 respectively. The relationship between complement regulator levels and negative symptoms was also observed in NAPLS2 alone (ß: 0.501, 95 % CI: -0.037, 1.039) and NAPLS3 alone, additionally adjusting for BMI (ß: 0.442, 95 % CI: 0.127, 0.757). CONCLUSION: The results indicate that plasma complement and coagulation regulator levels are prognostic factors of negative symptoms, independent of clinical and demographic prognostic factors. These results suggest complement and coagulation regulator levels could have potential utility in informing treatment decisions for negative symptoms in individuals at risk.

Global modified-Delphi consensus on comorbidities and prognosis of SCN8A-related epilepsy and/or neurodevelopmental disorders.

OBJECTIVES: We aimed to develop consensus on comorbidities (frequency, severity, and prognosis) and overall outcomes in epilepsy, development, and cognition for the five phenotypes of SCN8A-related disorders. METHODS: A core panel consisting of 13 clinicians, 1 researcher, and 6 caregivers was formed and split into three workgroups. One group focused on comorbidities and prognosis. All groups performed a literature review and developed questions for use in a modified-Delphi process. Twenty-eight clinicians, one researcher, and 13 caregivers from 16 countries participated in three rounds of the modified-Delphi process. Consensus was defined as follows: strong consensus ≥80% fully agree; moderate consensus ≥80% fully or partially agree, <10% disagree; and modest consensus 67%-79% fully or partially agree, <10% disagree. RESULTS: Consensus was reached on the presence of 14 comorbidities in patients with Severe Developmental and Epileptic Encephalopathy (Severe DEE) spanning non-seizure neurological disorders and other organ systems; impacts were mostly severe and unlikely to improve or resolve. Across Mild/Moderate Developmental and Epileptic Encephalopathy (Mild/Moderate DEE), Neurodevelopmental Delay with Generalized Epilepsy (NDDwGE), and NDD without Epilepsy (NDDwoE) phenotypes, cognitive and sleep-related comorbidities as well as fine and gross motor delays may be present but are less severe and more likely to improve compared to Severe DEE. There was no consensus on comorbidities in the SeL(F)IE phenotype but strong conesensus that seizures would largely resolve. Seizure freedom is rare in patients with Severe DEE but may occur in some with Mild/Moderate DEE and NDDwGE. SIGNIFICANCE: Significant comorbidities are present in most phenotypes of SCN8A-related disorders but are most severe and pervasive in the Severe DEE phenotype. We hope that this work will improve recognition, early intervention, and long-term management for patients with these comorbidities and provide the basis for future evidence-based studies on optimal treatments of SCN8A-related disorders. Identifying the prognosis of patients with SCN8A-related disorders will also improve care and quality-of-life for patients and their caregivers.

Mediation of meaningful outcomes in early intervention: a commentary on Carruthers et al. (2023).

Across the spectrum of behavioral, naturalistic developmental behavioral, and developmental/relational interventions for young children with autism, there has been limited empirical testing of the mechanism of these early intervention approaches. Testing mediation provides insights to the how or why the intervention condition may be preferred in comparison to a control in the population sample (Kraemer, American Journal of Psychiatry, 2016, 173, 672). Combined with an understanding of moderation (for whom or under what conditions), we move toward a better understanding of how to personalize interventions to build on strengths and maximize skill gains for autistic children. Yet, to date there are very few published texts of mechanism in early intervention for young children with autism. This commentary explores a recently published article by Carruthers et al (2023) and examines themes and considerations for measurement of intervention outcomes and mediators.

Annual Research Review: Early intervention viewed through the lens of developmental neuroscience.

The overarching goal of this paper is to examine the efficacy of early intervention when viewed through the lens of developmental neuroscience. We begin by briefly summarizing neural development from conception through the first few postnatal years. We emphasize the role of experience during the postnatal period, and consistent with decades of research on critical periods, we argue that experience can represent both a period of opportunity and a period of vulnerability. Because plasticity is at the heart of early intervention, we next turn our attention to the efficacy of early intervention drawing from two distinct literatures: early intervention services for children growing up in disadvantaged environments, and children at elevated likelihood of developing a neurodevelopmental delay or disorder. In the case of the former, we single out interventions that target caregiving and in the case of the latter, we highlight recent work on autism. A consistent theme throughout our review is a discussion of how early intervention is embedded in the developing brain. We conclude our article by discussing the implications our review has for policy, and we then offer recommendations for future research.

Commentary: A nurturing care perspective on bundling interventions - a reflection on Jeong et al. (2023).

Bundling multiple interventions have been implemented and evaluated in response to global recognition that young children benefit from the multiple components of nurturing care. Engaging Fathers for Effective Child Nutrition and Development in Tanzania Study evaluated the impact of adding a parenting intervention to a nutrition program and involving fathers on children's development. The study found that the bundled nutrition-parenting intervention improved children's short-term cognitive and receptive language scores over the nutrition only intervention, with no difference between involving mother-father couples versus mothers only. This study adds to recommendations for future multiple component interventions, including to investigate the mechanisms driving interventions, to address the potential for both benefits and harms, to involve household and community caregivers, and to incorporate implementation research to transition evidence-based programs to scale. Expanding nurturing care through multiple component interventions has the potential to promote equity by ensuring that all children have opportunities for healthy growth and development.

Mediation of 6-year mid-childhood follow-up outcomes after pre-school social communication (PACT) therapy for autistic children: randomised controlled trial.

BACKGROUND: There are very few mechanistic studies of the long-term impact of psychosocial interventions in childhood. The parent-mediated Paediatric Autism Communication Therapy (PACT) RCT showed sustained effects on autistic child outcomes from pre-school to mid-childhood. We investigated the mechanism by which the PACT intervention achieved these effects. METHODS: Of 152 children randomised to receive PACT or treatment as usual between 2 and 5 years of age, 121 (79.6%) were followed 5-6 years after the endpoint at a mean age of 10.5 years. Assessors, blind to the intervention group, measured Autism Diagnostic Observation Scale Calibrated Severity Score (ADOS CSS) for child autistic behaviours and Teacher Vineland (TVABS) for adaptive behaviour in school. Hypothesised mediators were child communication initiations with caregivers in a standard play observation (Dyadic Communication Measure for Autism, DCMA). Hypothesised moderators of mediation were baseline child non-verbal age equivalent scores (AE), communication and symbolic development (CSBS) and 'insistence on sameness' (IS). Structural equation modelling was used in a repeated measures mediation design. RESULTS: Good model fits were obtained. The treatment effect on child dyadic initiation with the caregiver was sustained through the follow-up period. Increased child initiation at treatment midpoint mediated the majority (73%) of the treatment effect on follow-up ADOS CSS. A combination of partial mediation from midpoint child initiations and the direct effect of treatment also contributed to a near-significant total effect on follow-up TVABS. No moderation of this mediation was found for AE, CSBS or IS. CONCLUSIONS: Early sustained increase in an autistic child's communication initiation with their caregiver is largely responsible for the long-term effects from PACT therapy on autistic and adaptive behaviour outcomes. This supports the theoretical logic model of PACT therapy but also illuminates fundamental causal processes of social and adaptive development in autism over time: early social engagement in autism can be improved and this can have long-term generalised outcome effects.

Effect of maternal prebiotic supplementation on human milk immunological composition: Insights from the SYMBA study.

BACKGROUND: Immunomodulatory proteins in human milk (HM) can shape infant immune development. However, strategies to modulate their levels are currently unknown. This study investigated whether maternal prebiotic supplementation alters the levels of immunomodulatory proteins in HM. METHODS: The study was nested within the SYMBA double-blind randomized controlled trial (ACTRN12615001075572), which investigated the effects of maternal prebiotic (short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides) supplementation from <21 weeks gestation during pregnancy until 6 months postnatal during lactation on child allergic disease risk. Mother-child dyads receiving prebiotics (n = 46) or placebo (n = 54) were included in this study. We measured the levels of 24 immunomodulatory proteins in HM collected at 2, 4, and 6 months. RESULTS: Cluster analysis showed that the overall immunomodulatory protein composition of milk samples from both groups was similar. At 2 months, HM of prebiotic-supplemented women had decreased levels of TGF-ß1 and TSLP (95% CI: -17.4 [-29.68, -2.28] and -57.32 [-94.22, -4.7] respectively) and increased levels of sCD14 (95% CI: 1.81 [0.17, 3.71]), when compared to the placebo group. At 4 months, IgG1 was lower in the prebiotic group (95% CI: -1.55 [-3.55, -0.12]) compared to placebo group. CONCLUSION: This exploratory study shows that prebiotic consumption by lactating mothers selectively alters specific immunomodulatory proteins in HM. This finding is crucial for understanding how prebiotic dietary recommendations for pregnant and lactating women can modify the immune properties of HM and potentially influence infant health outcomes through immune support from breastfeeding.

Psychosis metabolic risk calculator (PsyMetRiC) in early psychosis: External validation study in Finland.

INTRODUCTION: Accurate detection of cardiometabolic risk in early psychosis is crucial to reducing somatic morbidity and mortality in people with psychotic disorders. We conducted an external validation of the psychosis metabolic risk calculator (PsyMetRiC), a cardiometabolic risk prediction tool developed in the UK and tailored for young people with psychosis. We compared the predictive accuracy and clinical usefulness of PsyMetRiC and a general population-based risk prediction tool for type 2 diabetes, the Finnish Diabetes Risk Score (FINDRISC). METHODS: We included first-episode psychosis and ultra-high-risk for psychosis patients without metabolic syndrome aged 18-35 years from the Helsinki Early Psychosis and Turku Early Psychosis Study cohorts. We tested two versions of PsyMetRiC: the full model including age, sex, ethnicity, body-mass index, smoking status, prescription of metabolically-active antipsychotic medication, high-density lipoprotein, and triglyceride concentrations, and the partial-model excluding biochemical predictors, and the simplified FINDRISC including BMI, sex, systolic blood pressure, and fasting glucose. Discrimination, calibration, and decision curve analyses were used to assess the predictive performance and clinical usefulness of both PsyMetRiC and FINDRISC. We performed a site-specific re-calibration of PsyMetRiC (PsyMetRiC-Fi). RESULTS: The study sample consisted of 278 individuals (all White European ethnicity, 58.6% male, mean age 24.8 years, 37.8% smoking, mean BMI 23.5). Discrimination was marginally better in the PsyMetRiC full model (C = 0.72, 95% CI, 0.59-0.82) compared with partial model (C = 0.70, 95% CI 0.59-0.80) or FINDRISC (C = 0.63, 95% CI 0.54-0.71). Calibration plots displayed evidence of minor miscalibration for PsyMetRiC, which corrected following recalibration. Miscalibration was more pronounced for FINDRISC. Decision curve analysis showed that PsyMetRiC offers likely clinical usefulness in improving cardiometabolic risk management in early psychosis compared with giving everyone or no one an intervention. CONCLUSION: PsyMetRiC has utility in predicting cardiometabolic risk in Finnish patients with early psychosis. It has better discriminatory accuracy and offers more accurate risk prediction compared to other available strategies.

Speech based natural language profile before, during and after the onset of psychosis: A cluster analysis.

BACKGROUND AND HYPOTHESIS: Speech markers are digitally acquired, computationally derived, quantifiable set of measures that reflect the state of neurocognitive processes relevant for social functioning. "Oddities" in language and communication have historically been seen as a core feature of schizophrenia. The application of natural language processing (NLP) to speech samples can elucidate even the most subtle deviations in language. We aim to determine if NLP based profiles that are distinctive of schizophrenia can be observed across the various clinical phases of psychosis. DESIGN: Our sample consisted of 147 participants and included 39 healthy controls (HC), 72 with first-episode psychosis (FEP), 18 in a clinical high-risk state (CHR), 18 with schizophrenia (SZ). A structured task elicited 3 minutes of speech, which was then transformed into quantitative measures on 12 linguistic variables (lexical, syntactic, and semantic). Cluster analysis that leveraged healthy variations was then applied to determine language-based subgroups. RESULTS: We observed a three-cluster solution. The largest cluster included most HC and the majority of patients, indicating a 'typical linguistic profile (TLP)'. One of the atypical clusters had notably high semantic similarity in word choices with less perceptual words, lower cohesion and analytical structure; this cluster was almost entirely composed of patients in early stages of psychosis (EPP - early phase profile). The second atypical cluster had more patients with established schizophrenia (SPP - stable phase profile), with more perceptual but less cognitive/emotional word classes, simpler syntactic structure, and a lack of sufficient reference to prior information (reduced givenness). CONCLUSION: The patterns of speech deviations in early and established stages of schizophrenia are distinguishable from each other and detectable when lexical, semantic and syntactic aspects are assessed in the pursuit of 'formal thought disorder'.

Early specialised treatment for bipolar disorder: Long-term follow-up from the early intervention in affective disorders (EIA) randomised controlled trial.

BACKGROUND: It is unclear whether treatment early after onset in bipolar disorder may improve the long-term illness course. The early intervention in affective disorders (EIA) randomised controlled trial found that 2-years treatment in a specialised mood disorder clinic combining evidence-based pharmacological treatment with group psychoeducation improved clinical outcomes compared with standard treatment in patients with bipolar disorder discharged after their 1st, 2nd, or 3rd hospital admission. We aimed to assess the 16 years long-term outcomes after randomisation of the participants in the EIA trial. METHODS: Data were obtained by linking nation-wide Danish population-based registers. All 158 participants of the EIA trial (Trial Registration Number NCT00253071) were followed from time of randomisation (2005-2009) to end of study (31 December 2021). The primary outcome was risk of psychiatric readmission. Secondary outcomes were total admissions and costs, medication use, intentional self-harm or suicide attempt or suicide, and socio-economic measures. RESULTS: The absolute mean risk of psychiatric readmission was 49.3% in the intervention group and 59.8% in the control group, with no statistically significant difference between the groups (b = -0.10, 95% CI: -0.26 to 0.047, p = 0.18). Compared with the control group, patients in the intervention group had numerically fewer total admission days (mean (SD) 44 (77) versus 62 (109)), lower total cost of psychiatric hospital admissions and hospital-based outpatient visits (mean (SD) 22,001 (36793) euros versus 29,822 (52671) euros) and higher use of lithium and antipsychotics, but the differences were not statistically significant. Fewer patients in the intervention group had an event of intentional self-harm or suicide attempt or suicide during follow-up (OR 0.25, 95% CI: 0.15-0.40, p < 0.001) compared with the control group and more patients in the intervention group used antiepileptics (OR 2.21, 95% CI: 1.08-4.60, p = 0.031). CONCLUSION: Analyses of very long-term outcomes of the EIA trial may potentially indicate a beneficial effect of the intervention at the long term but were likely underpowered to detect a more subtle effect and for most outcomes the differences between groups were not statistically significant.

"Everyone screens to some extent": Barriers and facilitators of developmental screening among children with sickle cell disease: A mixed methods study.

BACKGROUND: Developmental delays are common among children with sickle cell disease (SCD). Existing guidelines support consistent screening to increase the identification of deficits and support referral to rehabilitative interventions, yet adherence remains variable. This study sought to assess current practices and identify barriers and facilitators to improve developmental screening for children 0-3 years with SCD. PROCEDURE: A mixed methods approach, guided by the Exploration and Preparation stages of the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework, assessed developmental screening practices among primary care providers and hematologists. Phase 1 included the SCD Developmental Surveillance and Screening Guideline and Practice Survey. Phase 2 included the SCD Developmental Screening Organizational Survey alongside semi-structured interviews. Descriptive and qualitative methods summarized the findings. RESULTS: Thirty-three providers from general pediatrics and hematology completed phase 1. Use of standardized developmental screening measures was variable, with the most frequently used being the Modified Checklist for Autism in Toddlers (77%) and the Ages and Stages Questionnaire (55%). Fifteen providers participated in phase 2, and reported they were most likely to engage in changes to improve their practice (mean = 4.4/5) and least likely to support spiritual health and well-being (mean = 3.5/5). Three themes emerged:(i) developmental screening is not standardized or specific to SCD, (ii) children with SCD benefit from a multidisciplinary team, and (iii) healthcare system limitations are a barrier. CONCLUSIONS: Developmental screening is inconsistent and insufficient for young children with SCD. Providers are interested in supporting children with SCD, but report a lack of standardized measures and consistent guidance as barriers.

"I was very scared when I found out my son had sickle cell": Caregiver knowledge and attitudes toward early intervention for young children with sickle cell disease: Implications for policy and practice from a multi-site study.

OBJECTIVE: This study characterized caregivers' beliefs related to early intervention services for children with sickle cell disease (SCD) to gain an indepth understanding of caregivers' experiences and desires for early intervention services. METHODS: Both qualitative and quantitative data were collected from caregivers of children aged 0-4 years with SCD across two sites in the United States. Caregivers completed the Knowledge of Infant Development Inventory, a custom survey about their experiences with early intervention, and a qualitative interview. RESULTS: A total of 127 caregivers were approached, 47 participated in surveys, and 20 completed interviews. Caregivers expressed varying levels of confidence and understanding of developmental milestones across sites. Interviews highlighted three main themes: fear of SCD-related complications, variable buy-in to early intervention, and the importance of provider-caregiver relationships. While some caregivers appreciated early intervention, others questioned its necessity. Caregivers communicated interest in connecting with other families facing similar challenges, emphasizing the need for increased awareness of available resources. CONCLUSIONS: Fear about their child's well-being was expressed by many caregivers, emphasizing the need for a supportive healthcare team that can help families connect with preventive interventions. While about a quarter of children had been referred to rehabilitation services, caregivers were unaware of the elevated risk for developmental delay, which diminished caregiver interest in participating in programs like early intervention. This study underscores the importance of addressing knowledge gaps and overcoming barriers to enhance care for families affected by SCD.

High consistency of cheating and honesty in early childhood.

Three preregistered studies examined whether 5-year-old children cheat consistently or remain honest across multiple math tests. We observed high consistency in both honesty and cheating. All children who cheated on the first test continued cheating on subsequent tests, with shorter cheating latencies over time. In contrast, 77% of initially honest children maintained honesty despite repeated failure to complete the tests successfully. A brief integrity intervention helped initially honest children remain honest but failed to dissuade initially cheating children from cheating. These findings demonstrate that cheating emerges early and persists strongly in young children, underscoring the importance of early prevention efforts. They also suggest that bolstering honesty from the start may be more effective than attempting to remedy cheating after it has occurred. RESEARCH HIGHLIGHTS: Our research examines whether 5-year-old children, once they have started cheating, will continue to do so consistently. We also investigate whether 5-year-old children who are initially honest will continue to be honest subsequently. We discovered high consistency in both honesty and cheating among 5-year-old children. Almost all the children who initially cheated continued this behavior, while those who were honest stayed honest. A brief integrity-boosting intervention successfully helped 5-year-old children maintain their honesty. However, the same intervention failed to deter cheaters from cheating again. These findings underscore the importance of implementing integrity intervention as early as possible, potentially before children have had their first experience of cheating.

How to Identify and Manage High-Risk Smoldering Multiple Myeloma.

PURPOSE OF REVIEW: It elucidates advancements in identifying and managing high-risk smoldering multiple myeloma (SMM), moving from observation strategies to intervention approaches. It highlights the significance of differentiating high-risk SMM from its less aggressive counterparts to prevent progression to multiple myeloma (MM). RECENT FINDINGS: Recent developments have improved SMM risk-stratification, integrating clinical, molecular and biological markers to identify high-risk individuals accurately. The advent of dynamic risk models that incorporate disease evolution and the application of novel diagnostic technologies are enhancing the understanding of SMM. Clinical trials exploring low to high intensity interventions, have shown promise in delaying MM onset and improving patient prognosis. There is a significant change in high-risk SMM management, leaning towards early intervention and precision medicine. The focus now is on refining these approaches, exploring new treatments, and proving the sustained benefits of early interventions to ultimately improve SMM patient care and outcomes.

Insomnia moderates the association between psychotic-like experiences and suicidal ideation in a non-clinical population: a network analysis.

Psychotic-like experiences (PLEs) have been associated with poor sleep quality and increased suicide risk. However, the association between PLEs, insomnia and suicide risk has not been thoroughly investigated in prior studies. In this study, we aimed to explore as to whether insomnia moderates the association between PLEs and suicidal ideation. The study was performed in 4203 young adults (aged 18-35 years, 63.8% females). Data were collected using self-reports. Moderation analysis demonstrated that PLEs are associated with higher levels of the current suicidal ideation only in participants with greater severity of insomnia (B = 0.003, p < 0.001). This analysis included age, gender, education, occupation and depressive symptoms as covariates. Moreover, the network analysis demonstrated that nodes representing PLEs are connected to the node of current suicidal ideation only in participants with greater severity of insomnia. The nodes of PLEs connected to the current suicidal ideation node captured PLEs representing deja vu experiences, auditory hallucination-like experiences and paranoia (edge weights between 0.011 and 0.083). Furthermore, nodes representing PLEs were the three most central nodes in the network analysis of individuals with higher levels of insomnia (strength centrality between 0.96 and 1.10). In turn, the three most central nodes were represented by depressive symptoms in the network analysis of individuals with lower levels of insomnia (strength centrality between 0.67 and 0.79). Findings from this study indicate that insomnia might be an important risk factor of suicide in people with PLEs, especially those reporting deja vu experiences, auditory hallucination-like experiences and paranoia.

Persistent negative symptoms in young people at clinical high risk of psychosis treated with an Italian early intervention program: a longitudinal study.

Negative symptoms in CHR-P people are generally not responsive to treatments and commonly related to poorer functional outcome. However, less research attention has been dedicated to Persistent Negative Symptoms (PNS), defined as clinically stable negative symptoms of moderate severity evident for at least 6 months. This study aims to (a) determine the prevalence of PNS in a sample of young people at CHR-P; (b) investigate any association of PNS with functioning and clinical features; (c) examine longitudinal course of PNS across 2 years of follow-up and changes in PNS severity levels with specialized treatments. One Hundred Eighty CHR-P participants were recruited and were divided into CHR-P/PNS + and CHR-P/PNS- subgroups. The clinical assessments were based on the PANSS and the GAF and were conducted at baseline and every 12 months during the follow-up. Twenty four participants showed PNS at entry. Of them, 21 concluded the 2-year follow-up period. At baseline, the CHR-P/PNS + participants showed more educational and employment deficits, and more social and functioning impairment. During the follow-up, the CHR-P/PNS + subgroup had a significant longitudinal decrease in negative symptoms, which was specifically related to antidepressant treatment. CHR-P/PNS + subjects also showed a higher incidence of new hospitalization and a lower functional recovery over time. Our findings support that the persistence of negative symptoms in CHR-P people is longitudinally related to worse daily functioning and more severe clinical conditions that are at higher risk of hospitalization and are less responsive to specialized treatments.