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.

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.

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.

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.

Childhood deprivation, health and development: associations with adult health in the 1958 and 1970 British prospective birth cohort studies.

OBJECTIVE: To examine the associations between childhood socioeconomic and family circumstances, health and behavioural and cognitive development, and health and mental well-being outcomes in adulthood; exploring whether associations are different for cohorts born in 1958 and 1970, or for men and women. DESIGN: Pooled analysis of two prospective, population-based, British birth cohort studies. PARTICIPANTS: 11 327 men and women born in 1958 and 11 177 men and women born in 1970 who responded in the adult follow-up investigations at ages 33 and 30 respectively. MAIN OUTCOME MEASURES: Self-rated general health, Rutter malaise scale indicating mental well-being, and presence of a long-standing illness limiting daily activities; assessed at ages 33 and 30 for the 1958 and 1970 birth cohorts respectively. RESULTS: A diversity of family background (socioeconomic deprivation, housing tenure, family disruption and parental interest), health and development (cognition and behaviour) measures each provided powerful independent indications for general health and mental well-being. Indications for limiting long-standing illness in adulthood were focused most strongly upon health difficulties in childhood. Few interactions between either birth cohort or gender and childhood measures were observed, and excepting these interactions consistency in associations between the childhood measures and the outcomes by gender and cohort was observable. CONCLUSIONS: This study emphasises the importance of cognitive and behavioural development in childhood, as well as deprivation, family background and childhood health in indicating future adult health and mental well-being, emphasising time-persistent effects and important indications for men and women.

Birth order and sibship size: evaluation of the role of selection bias in a case-control study of non-Hodgkin's lymphoma.

Substantial heterogeneity has been observed among case-control studies investigating associations between non-Hodgkin's lymphoma and familial characteristics, such as birth order and sibship size. The potential role of selection bias in explaining such heterogeneity is considered within this study. Selection bias according to familial characteristics and socioeconomic status is investigated within a United Kingdom-based case-control study of non-Hodgkin's lymphoma diagnosed during 1998-2001. Reported distributions of birth order and maternal age are each compared with expected reference distributions derived using national birth statistics from the United Kingdom. A method is detailed in which yearly data are used to derive expected distributions, taking account of variability in birth statistics over time. Census data are used to reweight both the case and control study populations such that they are comparable with the general population with regard to socioeconomic status. The authors found little support for an association between non-Hodgkin's lymphoma and birth order or family size and little evidence for an influence of selection bias. However, the findings suggest that between-study heterogeneity could be explained by selection biases that influence the demographic characteristics of participants.

Haplotype uncertainty in association studies.

Inferring haplotypes from genotype data is commonly undertaken in population genetic association studies. Within such studies the importance of accounting for uncertainty in the inference of haplotypes is well recognised. We investigate the effectiveness of correcting for uncertainty using simple methods based on the output provided by the PHASE haplotype inference methodology. In case-control analyses investigating non-Hodgkin lymphoma and haplotypes associated with immune regulation we find little effect of making adjustment for uncertainty in inferred haplotypes. Using simulation we introduce a higher degree of haplotype uncertainty than was present in our study data. The simulation represents two genetic loci, physically close on a chromosome, forming haplotypes. Considering a range of allele frequencies, degrees of linkage between the loci, and frequency of missing genotype data, we detail the characteristics of genetic regions which may be susceptible to the influence of haplotype uncertainty. Within our evaluation we find that bias is avoided by considering haplotype probabilities or using multiple imputation, provided that for each of these methods haplotypes are inferred separately for case and control populations; furthermore using multiple imputation provides the facility to incorporate haplotype uncertainty in the estimation of confidence intervals. We discuss the implications of our findings within the context of the complexity of haplotype inference for larger marker rich regions as would typically be encountered in genetic analyses.

Non-Hodgkin's lymphoma and family history of hematologic malignancy.

Familial aggregation of non-Hodgkin's lymphoma, and the co-occurrence of non-Hodgkin's lymphoma and other hematologic malignancies within families, provide evidence for genetic or common environmental etiologies for these conditions. The authors analyzed the association between non-Hodgkin's lymphoma risk and family history of hematologic malignancy using a case-control study based in the United Kingdom. The study recruited patients diagnosed with lymphoma during 1998-2001. Results indicated an increased risk of non-Hodgkin's lymphoma for persons with a positive family history of any hematologic malignancy (odds ratio = 1.70, 95% confidence interval: 1.08, 2.69) and particularly of any lymphoma (odds ratio = 2.43, 95% confidence interval: 1.14, 5.19). The authors compared the number of hematologic malignancies among relatives reported by the cases and controls with that expected from the national rates of hematologic malignancy registered in the United Kingdom. Through these comparisons, the authors raise questions about the validity of self-reported family history of hematologic malignancy, especially regarding identification of specific types of hematologic malignancies. Given these reservations, they consider how future epidemiologic studies may contribute to further understanding the role of familial susceptibility in non-Hodgkin's lymphoma.