Mental health problems in children with intellectual disability

Intellectual disability ranks in the top ten causes of disease burden globally and is the top cause in children younger than 5 years. 2-3% of children have an intellectual disability, and about 15% of children present with differences consistent with an intellectual disability (ie, global developmental delay and borderline intellectual functioning). In this Review, we discuss the prevalence of mental health problems, interventions to address these, and issues of access to treatment and services. Where possible, we take a global perspective, given most children with intellectual disability live in low-income and middle-income countries. Approximately 40% of children with intellectual disability present with a diagnosable mental disorder, a rate that is at least double that in children without intellectual disability. Most risk factors for poor mental health and barriers to accessing support are not unique to people with intellectual disability. With proportionate universalism as the guiding principle for reducing poor mental health at scale, we discuss four directions for addressing the mental health inequity in intellectual disability

Non-pharmacological and pharmacological interventions for the reduction or prevention of topographies of behaviours that challenge in people with intellectual disabilities:a systematic review and meta-analysis of randomised controlled trials

Background: People with intellectual disability show a high prevalence of behaviours that challenge. Clinical guidelines recommend that such behaviour should first be treated with non-pharmacological interventions, but research suggests off-label pharmaceuticals are commonly used. We aimed to evaluate the efficacy of non-pharmacological and pharmacological interventions for topographies of behaviours that challenge drawn from randomised controlled trials (RCTs). Methods: In this systematic review and meta-analysis, we searched PsycINFO, MEDLINE, Embase, CINAHL, and CENTRAL databases for RCT studies assessing an intervention (pharmacological or non-pharmacological) for behaviours that challenge (self-injury behaviour, aggression, destruction of property, irritability, and a composite overall measure) in participants with intellectual disability. The primary aim was to assess the efficacy of non-pharmacological and pharmacological interventions on behaviours that challenge. Secondary aims were to evaluate how effects varied over time and whether intervention, methodological, and participant characteristics moderate efficacy. We extracted standard mean difference (SMD) effect sizes (Cohen's d) from eligible studies and meta-analysed the data using a series of random effects models and subgroup analyses. This study was registered with PROSPERO 2021, CRD4202124997. Findings: Of 11 912 reports identified, 82 studies were included. 42 (51%) studies assessed non-pharmacological interventions and 40 (49%) assessed pharmacological interventions. Across all studies, 4637 people with intellectual disability aged 1–84 years (mean age 17·2 years) were included. 2873 (68·2%) were male, 1339 (28·9%) were female, and for 425 (9·2%) individuals, data on gender were not available. Data on ethnicity were unavailable. Small intervention effects were found for overall behaviours that challenge at post-intervention (SMD –0·422, 95% CI –0·565 to –0·279), overall behaviours that challenge at follow-up (–0·324, –0·551 to –0·097), self-injury behaviour at post-intervention (–0·238, –0·453 to –0·023), aggression at post-intervention (–0·438, –0·566 to –0·309), and irritability at post-intervention (–0·255, –0·484 to –0·026). No significant differences between non-pharmacological and pharmacological interventions were found for any topography of behaviours that challenge (all p&gt;0·05). Interpretation: A broad range of interventions for behaviours that challenge are efficacious with small effect sizes for people with intellectual disability. These findings highlight the importance of precision in the measurement of behaviours that challenge, and when operationalising intervention components and dosages. Funding: Cerebra.</p

IL-33 reduces the development of atherosclerosis

Atherosclerosis is a chronic inflammatory disease of the vasculature commonly leading to myocardial infarction and stroke. We show that IL-33, which is a novel IL-1–like cytokine that signals via ST2, can reduce atherosclerosis development in ApoE−/− mice on a high-fat diet. IL-33 and ST2 are present in the normal and atherosclerotic vasculature of mice and humans. Although control PBS-treated mice developed severe and inflamed atherosclerotic plaques in the aortic sinus, lesion development was profoundly reduced in IL-33–treated animals. IL-33 also markedly increased levels of IL-4, -5, and -13, but decreased levels of IFNγ in serum and lymph node cells. IL-33 treatment also elevated levels of total serum IgA, IgE, and IgG1, but decreased IgG2a, which is consistent with a Th1-to-Th2 switch. IL-33–treated mice also produced significantly elevated antioxidized low-density lipoprotein (ox-LDL) antibodies. Conversely, mice treated with soluble ST2, a decoy receptor that neutralizes IL-33, developed significantly larger atherosclerotic plaques in the aortic sinus of the ApoE−/− mice compared with control IgG-treated mice. Furthermore, coadministration of an anti–IL-5 mAb with IL-33 prevented the reduction in plaque size and reduced the amount of ox-LDL antibodies induced by IL-33. In conclusion, IL-33 may play a protective role in the development of atherosclerosis via the induction of IL-5 and ox-LDL antibodies

Perspectives of people with late age-related macular degeneration on mental health and mental wellbeing programmes: a qualitative study

People with age-related macular degeneration (AMD) experience high rates of depression, but rarely engage in or have access to tailored mental wellbeing programmes. This qualitative study investigated the perspectives of those primarily with late AMD on mental health and mental wellbeing programmes. Twenty-eight people with late AMD in at least one eye, and one person with early AMD in both eyes, aged 56-87 years (mean age 78 years) attending a private eye clinic between December 2019 and January 2020 in Sydney, New South Wales, Australia, participated. Individual semi-structured interviews were conducted and analysed deductively using content analysis, following the individual level factors for health promotion interventions in the behaviour change wheel: Capability (Physical & Psychological), Opportunity (Physical & Social), and Motivation (Reflective & Automatic). Six major themes were identified: Capability: (1) Impact of vision loss on mobility and leisure pursuits; (2) Adjustment to living with vision loss; Opportunity: (3) Program considerations for those with AMD; (4) Stigma and self-perception of vision loss and mental health; Motivation: (5) Accumulation of vision-related issues as a barrier to participation; (6) Examples of others living with vision loss. General personal factors relevant to delivery of a programme in this age group were also identified: Comorbidities; Limitations using technology; Isolation; Financial concerns and Beliefs that undesired effects of aging are inevitable. Complex individual, environmental and social factors influence the perspectives of people with late AMD on mental health, and potential participation in mental wellbeing programmes. These factors should be considered when developing and implementing mental wellbeing programmes to improve the emotional and functional rehabilitation outcomes for people with AMD. [Abstract copyright: © 2020 The Authors Ophthalmic and Physiological Optics © 2020 The College of Optometrists.

Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19

While it is now widely accepted that host inflammatory responses contribute to lung injury, the pathways that drive severity and distinguish coronavirus disease 2019 (COVID-19) from other viral lung diseases remain poorly characterized. We analyzed plasma samples from 471 hospitalized patients recruited through the prospective multicenter ISARIC4C study and 39 outpatients with mild disease, enabling extensive characterization of responses across a full spectrum of COVID-19 severity. Progressive elevation of levels of numerous inflammatory cytokines and chemokines (including IL-6, CXCL10, and GM-CSF) were associated with severity and accompanied by elevated markers of endothelial injury and thrombosis. Principal component and network analyses demonstrated central roles for IL-6 and GM-CSF in COVID-19 pathogenesis. Comparing these profiles to archived samples from patients with fatal influenza, IL-6 was equally elevated in both conditions whereas GM-CSF was prominent only in COVID-19. These findings further identify the key inflammatory, thrombotic, and vascular factors that characterize and distinguish severe and fatal COVID-19

Data quality and autism : issues and potential impacts

Introduction Large healthcare datasets can provide insight that has the potential to improve outcomes for patients. However, it is important to understand the strengths and limitations of such datasets so that the insights they provide are accurate and useful. The aim of this study was to identify data inconsistencies within the Hospital Episodes Statistics (HES) dataset for autistic patients and assess potential biases introduced through these inconsistencies and their impact on patient outcomes. The study can only identify inconsistencies in recording of autism diagnosis and not whether the inclusion or exclusion of the autism diagnosis is the error. Methods Data were extracted from the HES database for the period 1st April 2013 to 31st March 2021 for patients with a diagnosis of autism. First spells in hospital during the study period were identified for each patient and these were linked to any subsequent spell in hospital for the same patient. Data inconsistencies were recorded where autism was not recorded as a diagnosis in a subsequent spell. Features associated with data inconsistencies were identified using a random forest classifiers and regression modelling. Results Data were available for 172,324 unique patients who had been recorded as having an autism diagnosis on first admission. In total, 43.7 % of subsequent spells were found to have inconsistencies. The features most strongly associated with inconsistencies included greater age, greater deprivation, longer time since the first spell, change in provider, shorter length of stay, being female and a change in the main specialty description. The random forest algorithm had an area under the receiver operating characteristic curve of 0.864 (95 % CI [0.862 – 0.866]) in predicting a data inconsistency. For patients who died in hospital, inconsistencies in their final spell were significantly associated with being 80 years and over, being female, greater deprivation and use of a palliative care code in the death spell. Conclusions Data inconsistencies in the HES database were relatively common in autistic patients and were associated a number of patient and hospital admission characteristics. Such inconsistencies have the potential to distort our understanding of service use in key demographic groups

Antipsychotic medication versus psychological intervention versus a combination of both in adolescents with first-episode psychosis (MAPS): a multicentre, three-arm, randomised controlled pilot and feasibility study

Background Evidence for the effectiveness of treatments in early-onset psychosis is sparse. Current guidance for the treatment of early-onset psychosis is mostly extrapolated from trials in adult populations. The UK National Institute for Health and Care Excellence has recommended evaluation of the clinical effectiveness and cost-effectiveness of antipsychotic drugs versus psychological intervention (cognitive behavioural therapy [CBT] and family intervention) versus the combination of these treatments for early-onset psychosis. The aim of this study was to establish the feasibility of a randomised controlled trial of antipsychotic monotherapy, psychological intervention monotherapy, and antipsychotics plus psychological intervention in adolescents with first-episode psychosis. Methods We did a multicentre pilot and feasibility trial according to a randomised, single-blind, three-arm, controlled design. We recruited participants from seven UK National Health Service Trust sites. Participants were aged 14–18 years; help-seeking; had presented with first-episode psychosis in the past year; were under the care of a psychiatrist; were showing current psychotic symptoms; and met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service. Participants were assigned (1:1:1) to antipsychotics, psychological intervention (CBT with optional family intervention), or antipsychotics plus psychological intervention. Randomisation was via a web-based randomisation system, with permuted blocks of random size, stratified by centre and family contact. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions, and family intervention incorporated up to six sessions over 6 months. Choice and dose of antipsychotic were at the discretion of the treating consultant psychiatrist. Participants were followed up for a maximum of 12 months. The primary outcome was feasibility (ie, data on trial referral and recruitment, session attendance or medication adherence, retention, and treatment acceptability) and the proposed primary efficacy outcome was total score on the Positive and Negative Syndrome Scale (PANSS) at 6 months. Primary outcomes were analysed by intention to treat. Safety outcomes were reported according to as-treated status, for all patients who had received at least one session of CBT or family intervention, or at least one dose of antipsychotics. The study was prospectively registered with ISRCTN, ISRCTN80567433. Findings Of 101 patients referred to the study, 61 patients (mean age 16·3 years [SD 1·3]) were recruited from April 10, 2017, to Oct 31, 2018, 18 of whom were randomly assigned to psychological intervention, 22 to antipsychotics, and 21 to antipsychotics plus psychological intervention. The trial recruitment rate was 68% of our target sample size of 90 participants. The study had a low referral to recruitment ratio (around 2:1), a high rate of retention (51 [84%] participants retained at the 6-month primary endpoint), a high rate of adherence to psychological intervention (defined as six or more sessions of CBT; in 32 [82%] of 39 participants in the monotherapy and combined groups), and a moderate rate of adherence to antipsychotic medication (defined as at least 6 consecutive weeks of exposure to antipsychotics; in 28 [65%] of 43 participants in the monotherapy and combined groups). Mean scores for PANSS total at the 6-month primary endpoint were 68·6 (SD 17·3) for antipsychotic monotherapy (6·2 points lower than at randomisation), 59·8 (13·7) for psychological intervention (13·1 points lower than at randomisation), and 62·0 (15·9) for antipsychotics plus psychological intervention (13·9 points lower than at randomisation). A good clinical response at 6 months (defined as ≥50% improvement in PANSS total score) was achieved in four (22%) of 18 patients receiving antipsychotic monotherapy, five (31%) of 16 receiving psychological intervention, and five (29%) of 17 receiving antipsychotics plus psychological intervention. In as-treated groups, serious adverse events occurred in eight [35%] of 23 patients in the combined group, two [13%] of 15 in the antipsychotics group, four [24%] of 17 in the psychological intervention group, and four [80%] of five who did not receive any treatment. No serious adverse events were considered to be related to participation in the trial. Interpretation This trial is the first to show that a head-to-head clinical trial comparing psychological intervention, antipsychotics, and their combination is safe in young people with first-episode psychosis. However, the feasibility of a larger trial is unclear because of site-specific recruitment challenges, and amendments to trial design would be needed for an adequately powered clinical and cost-effectiveness trial that provides robust evidence