Sustained impact of a sleep intervention and moderators of treatment outcome for children with ADHD: a randomised controlled trial.

BACKGROUND: We aim to (1) determine whether a behavioural sleep intervention for children with attention-deficit/hyperactivity disorder (ADHD) leads to sustained benefits; and (2) examine the factors associated with treatment response. METHODS: This study was a randomised controlled trial of 244 children (5-13 years) with ADHD from Victoria, Australia. All participants had a moderate/severe sleep problem that met American Academy of Sleep Medicine criteria for an eligible sleep disorder by parent report. The two-session intervention covered sleep hygiene and standardised behavioural strategies. The control group received usual care. Parent- and teacher-reported outcomes at 12 months included sleep, ADHD severity, quality of life, daily functioning, behaviour, and parent mental health. Adjusted mixed effects regression analyses examined 12 month outcomes. Interaction analyses were used to determine moderators of intervention outcomes over time. The trial was registered with ISRCTN, http://www.controlled-trials.com (ISRCTN68819261). RESULTS: Intervention children were less likely to have a moderate/severe sleep problem by parent report at 12 months compared to usual care children (28.4% v. 46.5%, p = 0.03). Children in the intervention group fared better than the usual care group in terms of parent-reported ADHD symptoms (Cohen's d: -0.3, p < 0.001), quality of life (d: 0.4, p < 0.001), daily functioning (d: -0.5, p < 0.001), and behaviour (d: -0.3, p = 0.005) 12 months later. The benefits of the intervention over time in terms of sleep were less for children not taking ADHD medication and children with parents experiencing depression. CONCLUSIONS: A behavioural sleep intervention for ADHD is associated with small sustained improvements in child wellbeing. Children who are not taking ADHD medication or have parents with depression may require follow-up booster sleep sessions.

High prevalence of slight and mild hearing loss across mid-life: a cross-sectional national Australian study.

OBJECTIVES: Although presbycusis typically becomes symptomatic only in older age, slight and mild hearing loss may be detectable well before this. We studied current prevalence and characteristics of hearing loss in Australian mid-life adults. STUDY DESIGN: This was a population-derived national cross-sectional study nested within the Longitudinal Study of Australian Children. METHODS: A total of 1485 parents/guardians (87.3% female) aged 30-59 years underwent air-conduction audiometry. Hearing loss was defined in three ways to maximize cross-study comparability: high Fletcher index (mean of 1, 2 and 4 kHz; primary outcome relevant to speech perception), lower frequency (mean of 1 and 2 kHz) and higher frequency (mean of 4 and 8 kHz). Multivariable logistic regression examined how losses vary by age, sex and neighbourhood disadvantage. RESULTS: On high Fletcher index, 27.3% had bilateral and 23.8% unilateral thresholds >15 dB hearing level (HL) (slight or worse), and 4.9% had bilateral and 6.3% unilateral thresholds >25 dB HL (mild or worse). Bilateral higher frequency losses were more common than lower frequency losses for thresholds >15 dB HL (30.9% vs. 26.4%) and >25 dB HL (11.0% vs. 4.6%). Age increased the risk of bilateral speech and higher frequency losses (all P for trend < 0.05), but not lower frequency losses >25 dB HL. Although sex was not associated with speech and lower frequency losses, men were more likely to have bilateral higher frequency losses (e.g. >15 dB HL: odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.5-3.2, P < 0.001). CONCLUSIONS: Both slight and mild hearing loss show high and rising prevalence across mid-life. This offers opportunities to prevent progression to reduce the profound later burden of age-related hearing loss.

Mild-moderate congenital hearing loss: secular trends in outcomes across four systems of detection.

BACKGROUND: Universal newborn hearing screening (UNHS) targets moderate or greater hearing loss. However, UNHS also frequently detects children with mild loss that results in many receiving early treatment. The benefits of this approach are not yet established. We aimed to (i) compare language and psychosocial outcomes between four hearing loss detection systems for children aged 5-8 years with congenital mild-moderate hearing loss; (ii) determine whether age of detection predicts outcomes; and (iii) compare outcomes between children identified via well-established UNHS and the general population. METHODS: Linear regression adjusted for potential confounding factors was used throughout. Via a quasi-experimental design, language and psychosocial outcomes were compared across four population-based Australian systems of hearing loss detection: opportunistic detection, born 1991-1993, n = 50; universal risk factor referral, born 2003-2005, n = 34; newly established UNHS, born 2003-2005, n = 41; and well-established UNHS, born 2007-2010, n = 21. In pooled analyses, we examined whether age of detection predicted outcomes. Outcomes were similarly compared between the current well-established UNHS system and typically developing children in the Early Language in Victoria Study, born 2003, n = 1217. RESULTS: Age at diagnosis and hearing aid fitting fell steadily across the four systems. For moderate losses, mean expressive language (P for trend .05) and receptive vocabulary (P for trend .06) improved across the four systems, but benefit was not obvious for mild losses. In pooled analyses, diagnosis before age six months predicted better language outcomes for moderate losses. Children with mild-moderate losses exposed to well-established UNHS continue to experience expressive language scores well below children in the general population (adjusted mean difference -8.9 points, 95% CI -14.7 to -3.1). CONCLUSIONS: Treatment arising from UNHS appears to be clearly benefitting children with moderate hearing losses. However, rigorous trials are needed to quantify benefits, versus costs and potential harms, of early aiding of children with mild losses.

Changes in verbal and visuospatial working memory from Grade 1 to Grade 3 of primary school: Population longitudinal study.

BACKGROUND: Adaptive working memory training is being implemented without an adequate understanding of developmental trajectories of working memory. We aimed to quantify from Grade 1 to Grade 3 of primary school (1) changes in verbal and visuospatial working memory and (2) whether low verbal and visuospatial working memory in Grade 1 predicts low working memory in Grade 3. METHOD: The study design includes a population-based longitudinal study of 1,802 children (66% uptake from all 2,747 Grade 1 students) at 44 randomly selected primary schools in Melbourne, Australia. Backwards Digit Recall (verbal working memory) and Mister X (visuospatial working memory) screening measures from the Automated Working Memory Assessment (M = 100; SD = 15) were used to assess Grades 1 and 3 (ages 6-7 and 8-9 years) students. Low working memory was defined as ≥1 standard deviation below the standard score mean. Descriptive statistics addressed Aim 1, and predictive parameters addressed Aim 2. RESULTS: One thousand seventy (59%) of 1802 Grade 1 participants were reassessed in Grade 3. As expected for typically developing children, group mean standard scores were similar in Grades 1 and 3 for verbal, visuospatial, and overall working memory, but group mean raw scores increased markedly. Compared to "not low" children, those classified as having low working memory in Grade 1 showed much larger increases in both standard and raw scores across verbal, visuospatial, and overall working memory. Sensitivity was very low for Grade 1 low working memory predicting Grade 3 low classifications. CONCLUSION: Although mean changes in working memory standard scores between Grades 1 and 3 were minimal, we found that individual development varied widely, with marked natural resolution by Grade 3 in children who initially had low working memory. This may render brain-training interventions ineffective in the early school year ages, particularly if (as population-based programmes usually mandate) selection occurs within a screening paradigm.

The role of joint engagement in the development of language in a community-derived sample of slow-to-talk children.

We explored whether supported (SJE) or coordinated joint engagement (CJE) between mothers recruited from the community and their 24-month-old children who were slow-to-talk at 18 months old were associated with child language scores at ages 24, 36, and 48 months (n = 197). We further explored whether SJE or CJE modified the concurrent positive associations between maternal responsive behaviours and language scores. Previous research has shown that SJE, maternal expansions, imitations, and responsive questions were associated with better language scores. Our main finding was that SJE but not CJE was consistently positively associated with 24- and 36-month-old expressive and receptive language scores, but not with 48-month-old language scores. SJE modified how expansions and imitations, but not responsive questions, were associated with language scores; the associations were evident in all but the highest levels of SJE. Further research is necessary to test these findings in other samples before clinical recommendations can be made.

Extended B cell phenotype in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional study.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous condition of unknown aetiology characterized by multiple symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months. Recently, two clinical trials of B cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms. A possible but undefined role for B cells has therefore been proposed. Studies of the relative percentages of B cell subsets in patients with ME/CFS have not revealed any reproducible differences from healthy controls (HC). In order to explore whether more subtle alterations in B cell subsets related to B cell differentiation exist in ME/CFS patients we used flow cytometry to immunophenotype CD19⁺ B cells. The panel utilized immunoglobulin (Ig)D, CD27 and CD38 (classical B cell subsets) together with additional markers. A total of 38 patients fulfilling Canadian, Centre for Disease Control and Fukuda ME/CFS criteria and 32 age- and sex-matched HC were included. We found no difference in percentages of classical subsets between ME/CFS patients and HC. However, we observed an increase in frequency (P < 0·01) and expression (MFI; P = 0·03) of CD24 on total B cells, confined to IgD⁺ subsets. Within memory subsets, a higher frequency of CD21⁺ CD38⁻ B cells (> 20%) was associated with the presence of ME/CFS [odds ratio: 3·47 (1·15-10·46); P = 0·03] compared with HC, and there was a negative correlation with disease duration. In conclusion, we identified possible changes in B cell phenotype in patients with ME/CFS. These may reflect altered B cell function and, if confirmed in other patient cohorts, could provide a platform for studies based on clinical course or responsiveness to rituximab therapy.

Human adipose tissue-derived mesenchymal stem cells abrogate plasmablast formation and induce regulatory B cells independently of T helper cells.

Mesenchymal or stromal stem cells (MSC) interact with cells of the immune system in multiple ways. Modulation of the immune system by MSC is believed to be a therapeutic option for autoimmune disease and transplant rejection. In recent years, B cells have moved into the focus of the attention as targets for the treatment of immune disorders. Current B-cell targeting treatment is based on the indiscriminate depletion of B cells. The aim of this study was to examine whether human adipose tissue-derived MSC (ASC) interact with B cells to affect their proliferation, differentiation, and immune function. ASC supported the survival of quiescent B cells predominantly via contact-dependent mechanisms. Coculture of B cells with activated T helper cells led to proliferation and differentiation of B cells into CD19(+) CD27(high) CD38(high) antibody-producing plasmablasts. ASC inhibited the proliferation of B cells and this effect was dependent on the presence of T cells. In contrast, ASC directly targeted B-cell differentiation, independently of T cells. In the presence of ASC, plasmablast formation was reduced and IL-10-producing CD19(+) CD24(high) CD38(high) B cells, known as regulatory B cells, were induced. These results demonstrate that ASC affect B cell biology in vitro, suggesting that they can be a tool for the modulation of the B-cell response in immune disease.

Vulnerability to intimate partner violence and poor mental health in the first 4-year postpartum among mothers reporting childhood abuse: an Australian pregnancy cohort study.

The purpose of this study was to investigate intergenerational patterns of abuse and trauma and the health consequences for women in the early childbearing years. A prospective pregnancy cohort of 1507 nulliparous women (≦24 weeks gestation) were recruited in Melbourne, Australia, 2003-2005. Follow-up was scheduled in late pregnancy, 3-, 6- and 12-month and 4-year postpartum. Childhood abuse was retrospectively reported at 4-year postpartum using the Child Maltreatment History Self Report. Intimate partner violence (IPV) was assessed at 1- and 4-year postpartum with the Composite Abuse Scale. Maternal depressive symptoms were assessed in all follow-ups using the Edinburgh Postnatal Depression Scale. Multivariable logistic regression was used to examine associations between childhood abuse, maternal mental health and IPV. Childhood abuse was reported by 41.1 % of women. In the 4 years after having their first child, 28.2 % of women reported IPV, 25.2 % depression and 31.6 % anxiety. Childhood abuse was associated with odds of depression or anxiety 1.5-2.6 times greater and 1.8-3.2 times greater for IPV. Childhood physical abuse remained significantly associated with depression and anxiety in pregnancy and postpartum after adjusting for IPV and stressful life events, while sexual abuse remained significantly associated only with anxiety. Women who begin childbearing with a history of childhood abuse are more vulnerable to IPV and poor mental health. All health care services and agencies in contact with children, young people and families should have adequate training to identify trauma associated with abuse and IPV and provide first line supportive care and referral.

Maternal depression from early pregnancy to 4 years postpartum in a prospective pregnancy cohort study: implications for primary health care.

OBJECTIVE: To describe the prevalence of maternal depression from pregnancy to 4 years postpartum, and the risk factors for depressive symptoms at 4 years postpartum. DESIGN: Prospective pregnancy cohort study of nulliparous women. SETTING: Melbourne, Australia. SAMPLE: In all, 1507 women completed baseline data in pregnancy (mean gestation 15 weeks). METHODS: Women were recruited from six public hospitals. Questionnaires were completed at recruitment and 3, 6, 12 and 18 months postpartum, and 4 years postpartum. MAIN OUTCOME MEASURES: Scores ≥13 on the Edinburgh Postnatal Depression Scale were used to indicate depressive symptoms. RESULTS: Almost one in three women reported depressive symptoms at least once in the first 4 years after birth. The prevalence of depressive symptoms at 4 years postpartum was 14.5%, and was higher than at any time-point in the first 12 months postpartum. Women with one child at 4 years postpartum were more likely to report depressive symptoms at this time compared with women with subsequent children (22.9 versus 11.3%), and this association remained significant in adjusted models (Adjusted odds ratio 1.71, 95% confidence interval 1.12-2.63). CONCLUSIONS: Maternal depression is more common at 4 years postpartum than at any time in the first 12 months postpartum, and women with one child at 4 years postpartum report significantly higher levels of depressive symptoms than women with subsequent children. There is a need for scaling up of current services to extend surveillance of maternal mental health to cover the early years of parenting.

Developmental vulnerability--don't investigate without a model in mind.

Children who are developmentally vulnerable are at risk of a difficult start to school, and ongoing educational challenges which may adversely impact on long term health outcomes. Clinicians, researchers and service providers need a thorough understanding of both risk and protective factors and their complex interplay to understand their impact on early childhood development, in order to plan effective and comprehensive prevention and interventions strategies. In this opinion piece we recommend that investigation of developmental vulnerability should only proceed if underpinned by both a theoretical model through which the interaction between risk and protective factors may be investigated, and analytical models that are appropriate to assess these impacts.