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.

Intergenerational Impacts of Family Violence - Mothers and Children in a Large Prospective Pregnancy Cohort Study.

BACKGROUND: Violence and other adversities commonly co-occur, yet are usually investigated individually. The primary objectives of this paper are to investigate: (i) the relationship between maternal exposure to violence (including childhood abuse and intimate partner violence) and postpartum mental and physical health; and (ii) the extent to which exposure to violence and poor maternal mental and physical health are associated with children's emotional-behavioral difficulties. METHODS: Prospective pregnancy cohort (n = 1507) followed up to 4 year postpartum. Validated measures used: Composite Abuse Scale; Edinburgh Postnatal Depression Scale, SF-36, Child Maltreatment History Self Report; Strengths and Difficulties Questionnaire. Logistic regression was used to investigate associations between maternal childhood abuse, intimate partner violence (IPV), maternal health and child emotional and behavioral difficulties at age 4. OUTCOMES: Two out of five women (41%) reported abuse in childhood, and almost one in three (29%) reported IPV during the first four years of motherhood. Women reporting both physical and sexual childhood abuse had markedly raised odds of IPV and poor physical and mental health at all time points (pregnancy, first year postpartum and four year postpartum). For the index child, violence exposures (maternal childhood abuse or IPV) and poor maternal physical or mental health were associated with higher odds of emotional/behavioral difficulties at age four. In multivariable models (adjusted for child gender and maternal age), cumulative exposures (multiple violence exposures or poor maternal mental or physical health at multiple time points) each independently added to increased odds of emotional-behavioral difficulties. Children of mothers who reported a history of childhood abuse but were not exposed to IPV had odds of difficulties similar to children of mothers not reporting any violence exposure, suggesting resilient outcomes where violence experiences are not repeated in the next generation. INTERPRETATION: The clustering of risk (child and adult violence experiences) and the accumulation of risk within families (IPV, poor maternal health, child difficulties) highlight the need for effective early intervention to limit or ameliorate the impact of violence across the lifespan, and to break the intergenerational cycle of disadvantage.

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.

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.

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.

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.

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.

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.

Association between sleep and working memory in children with ADHD: a cross-sectional study.

OBJECTIVE/BACKGROUND: This study aimed to examine the relationship between sleep problems and working memory in children aged 5-13 years with attention-deficit/hyperactivity disorder (ADHD). PATIENTS/METHODS: Children with ADHD were recruited into a randomized controlled trial from 21 paediatric practices in VIC, Australia. Cross-sectional data for intervention and control children were pooled at 6 months post randomization for the current analyses (n = 189). Children who met the Diagnostic Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for ADHD and had a parent-reported moderate/severe sleep problem that fulfilled diagnostic criteria for a behavioural sleep disorder were recruited into the study. Sleep was assessed by detailed parent (Children's Sleep Habits Questionnaire) and self-reports (Self-Sleep Report). Working memory was measured using the Working Memory Test Battery for Children (low and very low working memory defined as <25th and <10th percentiles, respectively). Analyses were adjusted for child age and gender, internalizing and externalizing comorbidities, and socio-economic status. RESULTS: Self-reported sleep problem severity was associated with poorer working memory; for each standard deviation increase in self-reported sleep problems, working memory scores decreased by -3.8 points (95% confidence interval (CI): -6.7, -0.8; p = 0.01). There was some evidence that self-reported sleep problems were associated with low (p = 0.06) and very low working memory (p = 0.01). There was minimal evidence that parent-reported sleep problems were associated with poorer working memory with the exception of bedtime resistance problems. CONCLUSIONS: Behavioural sleep problems and working memory are associated in children with ADHD, particularly when sleep is assessed by self-report.

Prevalence of metabolic syndrome in type 2 diabetes mellitus patients.

BACKGROUND: The diabetic condition is influenced by several factors, some of which can accelerate the disease's progression to various complications that aggravate the morbidity. AIMS: This study aimed at determining the prevalence of metabolic syndrome (MetS) and its individual components and the most critical predictive risk factors of MetS in type 2 diabetic patients. MATERIALS AND METHODS: This cross-sectional study involved 150 type 2 diabetes mellitus patients and was conducted at the Diabetes Centre of the Komfo Anokye Teaching Hospital in Kumasi, the Ashanti Region of Ghana, from February, 2013 to April, 2013. The study involved the use of a questionnaire to obtain some information on the diabetics, undertaking anthropometric measurements, as well as collecting blood samples for the measurement of some biochemical parameters; fasting blood glucose and lipid profile. MetS was defined according to the National Cholesterol Education Program/Adult Treatment Panel III criteria. RESULTS: The prevalence of MetS was 58% in the studied Ghanaian population. Hypertension was the commonest risk factor (60%), followed by central obesity (48.67%) and dyslipidemia (37%). Female type 2 diabetics had a higher prevalence of MetS, and carried more components than their male counterparts. Regression analysis showed three factors; femininity, high body mass index and low educational status were the most critical predictive risk factors of MetS, according to this study. CONCLUSION: With hypertension being the commonest component, future cardiovascular disease prevention strategies should focus attention on its management and prevention, through education.

Plasma Levels of Uric Acid, Urea and Creatinine in Diabetics Who Visit the Clinical Analysis Laboratory (CAn-Lab) at Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.

INTRODUCTION: Diabetes mellitus is one of the most common metabolic diseases worldwide. This metabolic disorder contributes greatly to the significant proportion of the burden of renal damage and dysfunction. The aim of the study was to investigate the renal function of the diabetic patients who visit the Clinical Analysis Laboratory (CAn-Lab) at the Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana. MATERIALS AND METHODS: Demographic data as well as medical history were obtained through the administration of a questionnaire. Anthro-pometric measurements were taken and blood samples were analysed for glucose, uric acid, urea and creatinine. Data collected were analysed using SPSS version 16.0. RESULTS: A total of 34 diabetic patients, aged from 40-77 y were recruited, 22 (64.7%) of them were males with mean age of 57.40 ± 11.8 y (±SD), while 12 (35.3%) were females with mean age of 58.17 ± 7.47 y. There was a statistically significant difference between the mean duration of the disease, as the females had longer duration, 12.50 ± 6.95 y, as compared to 7.32 ± 4.48 y in males (p=0.033). The mean plasma creatinine level in the females was 84.17 ± 54.73 µmol/l. In the diabetic population, there was a positive correlation between age and plasma creatinine level, (r=0.375, p=0.029). In the female diabetics, there was a positive correlation between fasting blood sugar (FBS) and the measured metabolic end products (r>0.5, p<0.05), a positive correlation between body mass index (BMI) and uric acid (r=0.576, p=0.005) and a positive correlation between BMI and FBS (r= 0.625, p= 0.030). CONCLUSION: Our results on the parameters measured; show that the diabetic population was experiencing mild kidney dysfunction, compared to non-diabetic controls.

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.

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.

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.

Behavioural sleep problems in children with attention-deficit/hyperactivity disorder (ADHD): protocol for a prospective cohort study.

INTRODUCTION: Children with attention-deficit/hyperactivity disorder (ADHD) commonly experience behavioural sleep problems, yet these difficulties are not routinely assessed and managed in this group. Presenting with similar symptoms to ADHD itself, sleep problems are complex in children with ADHD and their aetiology is likely to be multifactorial. Common internalising and externalising comorbidities have been associated with sleep problems in children with ADHD; however, this relationship is yet to be fully elucidated. Furthermore, limited longitudinal data exist on sleep problems in children with ADHD, thus their persistence and impact remain unknown. In a diverse sample of children with ADHD, this study aims to: (1) quantify the relationship between sleep problems and internalising and externalising comorbidities; (2) examine sleep problem trajectories and risk factors; and (3) examine the longitudinal associations between sleep problems and child and family functioning over a 12-month period. METHODS AND ANALYSIS: A prospective cohort study of 400 children with ADHD (150 with no/mild sleep problems, 250 with moderate/severe sleep problems) recruited from paediatric practices across Victoria, Australia. The children's parents and teacher provide data at baseline and 6-month and 12-month post enrolment. KEY MEASURES: Parent report of child's sleep problem severity (no, mild, moderate, severe); specific sleep domain scores assessed using the Child Sleep Habits Questionnaire; internalising and externalising comorbidities assessed by the Anxiety Disorders Interview Schedule for Children IV/Parent version. ANALYSES: Multiple variable logistic and linear regression models examining the associations between key measures, adjusted for confounders identified a priori. ETHICS AND DISSEMINATION: Ethics approval has been granted. Findings will contribute to our understanding of behavioural sleep problems in children with ADHD. Clinically, they could improve the assessment and management of sleep problems in this group. We will seek to publish in leading paediatric journals, present at conferences and inform Australian paediatricians through the Australian Paediatric Research Network.

Community-based healthcare costs for children born low birthweight, preterm and/or small for gestational age: data from the Longitudinal Study of Australian Children.

AIM: Children born low birthweight, preterm and/or small for gestational age (SGA) sustain substantially increased costs for hospital-based health care and additional educational support in the first few years of life. This is the first study internationally to investigate costs beyond hospital care, to community-based health care and prescription medicines across early and middle childhood with actual cost data, and to examine these costs according to the severity of perinatal risk. METHOD: In the prospective Longitudinal Study of Australian Children, we followed two cohorts of children from age of 0 to 5 years (no increased perinatal risk, n = 3973; mild risk, n = 442; and moderate-to-high risk, n = 297), and from age of 4 to 9 years (no increased perinatal risk, n = 3629; mild risk, n = 465; and moderate-to-high risk, n = 361). Children were defined as mild risk if born 32-36 weeks, with birthweight 1500-2499 g, and/or SGA (<5-9th percentile), and moderate-to-high risk if born <32 weeks, birthweight <1500 g and/or extremely SGA (<5th percentile). Federal government expenditure (2011 $AUD) on healthcare attendances and prescription medication from birth to 9 years were calculated via data linkage to the Australian Medicare records. RESULTS: Mean costs per child were A$362 higher (95% CI $156; 568) from 0 to 5 years and A$306 higher (95% CI $137; 475) from 4 to 9 years, for children with any compared with no increased perinatal risk (P < 0.001). At the population level, an additional A$32m was spent per year for children 0-9 years with any relative to no increased perinatal risk. CONCLUSIONS: Perinatal risk is a major public health issue conferring considerable additional expense to community-based health care, most marked in the first year of life but persisting up to at least 10 years. Even without additionally considering burden, these findings add to the urgency of identifying effective mechanisms to reduce perinatal risk across its full spectrum.

Primary healthcare costs associated with sleep problems up to age 7 years: Australian population-based study.

OBJECTIVES: In Australian 0-7-year olds with and without sleep problems, to compare (1) type and costs to government of non-hospital healthcare services and prescription medication in each year of age and (2) the cumulative costs according to persistence of the sleep problem. DESIGN: Cross-sectional and longitudinal data from a longitudinal population study. SETTING: Data from two cohorts participating in the first two waves of the nationally representative Longitudinal Study of Australian Children. PARTICIPANTS: Baby cohort at ages 0-1 and 2-3 (n=5107, 4606) and Kindergarten cohort at ages 4-5 and 6-7 (n=4983, 4460). MEASUREMENTS: Federal Government expenditure on healthcare attendances and prescription medication from birth to 8 years, calculated via linkage to Australian Medicare data, were compared according to parent report of child sleep problems at each of the surveys. RESULTS: At both waves and in both cohorts, over 92% of children had both sleep and Medicare data. The average additional healthcare costs for children with sleep problems ranged from $141 (age 5) to $43 (age 7), falling to $98 (age 5) to $18 (age 7) per child per annum once family socioeconomic position, child gender, global health and special healthcare needs were taken into account. This equates to an estimated additional $27.5 million (95% CI $9.2 to $46.8 million) cost to the Australian federal government every year for all children aged between 0 and 7 years. In both cohorts, costs were higher for persistent than transient sleep problems. CONCLUSIONS: Higher healthcare costs were sustained by infants and children with sleep problems. This supports ongoing economic evaluations of early prevention and intervention services for sleep problems considering impacts not only on the child and family but also on the healthcare system.

Bidirectional associations between overweight and health-related quality of life from 4-11 years: Longitudinal Study of Australian Children.

BACKGROUND: Temporal pathways of known associations between overweight and poor health-related quality of life (HRQoL) in adolescents remain poorly documented. This study aims to (1) examine timing and strength of the association between HRQoL and body mass index (BMI) in childhood, and (2) investigate directionality and impact of cumulative burden in any observed HRQoL-BMI associations. DESIGN, SETTING AND PARTICIPANTS: Participants were 3898 children in the population-based Longitudinal Study of Australian Children (LSAC) assessed at four biennial waves from ages 4-5 (2004) to 10-11 years (2010). MAIN MEASURES: At every wave, parents completed the Pediatric Quality of Life Inventory, and measured BMI (kg m(-2)) was converted into BMIz and overweight using international norms. ANALYSES: Linear and logistic regressions. RESULTS: Overweight first became cross-sectionally associated with HRQoL at 6-7 years of age, with linear associations between poorer HRQoL (physical and psychosocial health) and higher BMI developing by 8-9 years and strengthening by 10-11 years. Longitudinal analyses revealed cumulative relationships such that the number of times a child was overweight between the ages 4 and 11 years predicted progressively poorer scores on both physical and psychosocial health at 10-11 years (P-values for trend <0.001). In the weaker reverse associations, children with poor (vs persistently good) physical health at any wave had slightly higher mean BMIz at age 10-11 years, but this difference was small (0.14, 95% confidence interval (CI): 0.04, 0.24) and not cumulative; results for psychosocial health were even weaker, with mixed subscale findings. CONCLUSIONS: Middle childhood appears to be the critical period in which HRQoL-BMI comorbidities emerge and strengthen, first among children with clinically relevant conditions, that is, overweight or poor HRQoL, and then more generally across the whole range of BMI. Poorer HRQoL seemed predominantly a consequence of higher BMI, rather than a cause, suggesting that effective promotion of healthy weight could benefit multiple aspects of children's well-being.

Maternal general health and children's cognitive development and behaviour in the early years: findings from the Millennium Cohort Study.

BACKGROUND: Mothers often experience physical and psychological difficulties during the post-natal period and these may continue through the early years of raising children and have negative effects on engagement and caregiving. Pathways between maternal depression, parental engagement and caregiving and children's subsequent development have been described in longitudinal studies; yet, less is known about how other aspects of maternal health may influence children's development. METHODS: A longitudinal analysis within the Millennium Cohort Study was conducted including 7906 families from England. Maternal general health and psychological well-being were assessed when their children were 9 months and 3 years old, socio-demographic characteristics were assessed at 9 months, and engagement and caregiving were assessed at 3 years. These were examined as predictors of children's learning and development and behaviour at age 5. RESULTS: There are clear associations between maternal general health and children's development with regard to both learning and development and behaviour. These effects are reduced if psychological distress is taken into account; yet, maternal general health maintains importance as a predictor for children's subsequent development. There is evidence of an association via engagement and caregiving which links maternal health to children's development and evidence of the influence of underlying socio-demographic disadvantage. CONCLUSION: General maternal health as well as psychological well-being during the early years of raising children may be influential for children's development. This study suggests the need for a broader recognition of maternal health as well as psychological well-being as a foundation for family well-being, and speaks to support for mothers in maintaining engagement and caregiving for their children during periods of ill health.

Simulation and modeling of laser-tissue interactions based on a liposome-dye system.

This work presents an overview of the use of liposomes for targeted delivery of photosensitizers to tumors for Photodynamic Therapy (PDT). It assesses the results of a quantitative model to explain the interaction of short-pulsed lasers (in the nanosecond and picosecond domains) with a liposome-dye complex in terms of a localized photo-induced thermal mechanism. Incorporation of an organic dye (sulforhodamine) within lipid vesicles has been investigated in conjunction with the effect of laser irradiation on the integrity of the liposome-dye complex. The variation of the absorption coefficient as a function of wavelength for dye-encapsulated liposomes before and after laser-induced release of dye was studied and modeled. The commercial software Mathematica was used to develop a Gaussian model for the energy absorption by the liposome-dye complex. Dye release from 3 microm - liposome encapsulating 25 mM aqueous solution of sulforhodamine dye was studied using 8 ns laser pulses at the second harmonic of the Nd:YAG laser (at 532 nm) and compared with dye release employing 25 ps - laser pulses. In addition, the temperature-dependence of the dye release has been included in the photo-thermal model.