Some factors affecting rubella seronegative prevalence among pregnant women in a North West England region between April 2011 and March 2013.

BACKGROUND: Rubella is usually a mild viral illness, but during pregnancy, it can have potentially devastating effects causing fetal losses and severe congenital malformations (congenital rubella syndrome). Rubella is now rare in most developed countries following a successful vaccination programme. We aimed to investigate differences in epidemiological profile of pregnant women screened antenatally in Liverpool to identify risk factors for rubella immunity. METHODS: All samples were tested with the Elecsys Rubella IgG immunoassay kit. A result <10 IU/ml was considered to be seronegative. RESULTS: The seronegativity prevalence among pregnant women in Liverpool (6.3%) is higher than average value for the North West region (3.7%). The seronegative rates varied with age (15.4% for <15 years, 18.7% for 15-20 years, compared with 2% for 30-35 years). The areas with the highest seronegative rates correspond with areas of Liverpool with high pockets of socioeconomic deprivation. CONCLUSION: The highest proportion of seronegative women were among the youngest age groups. Local areas with highest level of deprivation should be given priority and additional resources to develop targeted programmes and pathways to implement appropriate interventions such as MMR catch-up programmes and put in place arrangements for offering MMR vaccination in maternity units.

ADHD in children and adolescents: Review of current practice of non-pharmacological and behavioural management.

Attention deficit Hyperactivity Disorder (ADHD) is the commonest childhood neurodevelopmental disorder, affecting 3 to 9% by school age, and often persists into adulthood. ADHD in children and young people (CYP) has wide ranging multi-modal impacts on the affected CYP, their carers and the society. Co-morbidity with other neurodevelopmental, behavioural and emotional disorders is the rule rather than exception. Pharmacological treatment is not recommended as the sole therapeutic intervention, and several other non-pharmacological interventions have been advocated within a framework of Multi-modal strategy as the norm, to address both the core symptoms as well as the behavioural and other related difficulties. All paediatric professionals need to be familiar with the principles of different modalities of non-pharmacological or behavioural interventions for managing ADHD in CYP. Most published up-to-date evidence for behavioural interventions both for the core ADHD symptoms and other outcome measures are summarized in this article, including the peculiar problems related to their research. The most effective evidence-based strategies for controlling ADHD core symptoms are combination of stimulant medications with Behavioural therapy (BT) or Cognitive behaviour therapy (CBT), as well as group-based parental Psychoeducation. Standalone BT, CBT, Mindfulness, Neurocognitive training and Neurofeedback cannot currently be recommended for controlling core symptoms due to limited evidence. Other Behavioural interventions could lead to improvements in ADHD-related outcomes, including parenting skills, CYP's social skills, academic performance and disruptive behaviours. School-based non-pharmacological interventions have been shown to reduce disruptive behaviours. Executive skills are also significantly improved with use of computer-based Neurocognitive training and regular physical Cardio exercises. It is disappointing that combinations of different types of psychosocial interventions have low efficacy on both the core ADHD symptoms and other related outcomes. The readers are welcome to test their knowledge and learning efficacy through an accompanying quiz.

Management of sleep disorders among children and adolescents with neurodevelopmental disorders: A practical guide for clinicians.

There is a complex relationship between sleep disorders and childhood neurodevelopmental, emotional, behavioral and intellectual disorders (NDEBID). NDEBID include several conditions such as attention deficit/hyperactivity disorder, autism spectrum disorder, cerebral palsy, epilepsy and learning (intellectual) disorders. Up to 75% of children and young people (CYP) with NDEBID are known to experience different types of insomnia, compared to 3% to 36% in normally developing population. Sleep disorders affect 15% to 19% of adolescents with no disability, in comparison with 26% to 36% among CYP with moderate learning disability (LD) and 44% among those with severe LD. Chronic sleep deprivation is associated with significant risks of behavioural problems, impaired cognitive development and learning abilities, poor memory, mood disorders and school problems. It also increases the risk of other health outcomes, such as obesity and metabolic consequences, significantly impacting on the wellbeing of other family members. This narrative review of the extant literature provides a brief overview of sleep physiology, aetiology, classification and prevalence of sleep disorders among CYP with NDEBIDs. It outlines various strategies for the management, including parenting training/psychoeducation, use of cognitive-behavioral strategies and pharmacotherapy. Practical management including assessment, investigations, care plan formulation and follow-up are outlined in a flow chart.

Classification, prevalence and integrated care for neurodevelopmental and child mental health disorders: A brief overview for paediatricians.

'Neurodevelopmental disorders' comprise a group of congenital or acquired long-term conditions that are attributed to disturbance of the brain and or neuromuscular system and create functional limitations, including autism spectrum disorder, attention deficit/ hyperactivity disorder, tic disorder/ Tourette's syndrome, developmental language disorders and intellectual disability. Cerebral palsy and epilepsy are often associated with these conditions within the broader framework of paediatric neurodisability. Co-occurrence with each other and with other mental health disorders including anxiety and mood disorders and behavioural disturbance is often the norm. Together these are referred to as neurodevelopmental, emotional, behavioural, and intellectual disorders (NDEBIDs) in this paper. Varying prevalence rates for NDEBID have been reported in developed countries, up to 15%, based on varying methodologies and definitions. NDEBIDs are commonly managed by either child health paediatricians or child/ adolescent mental health (CAMH) professionals, working within multidisciplinary teams alongside social care, education, allied healthcare practitioners and voluntary sector. Fragmented services are common problems for children and young people with multi-morbidity, and often complicated by sub-threshold diagnoses. Despite repeated reviews, limited consensus among clinicians about classification of the various NDEBIDs may hamper service improvement based upon research. The recently developed "Mental, Behavioural and Neurodevelopmental disorder" chapter of the International Classification of Diseases-11 offers a way forward. In this narrative review we search the extant literature and discussed a brief overview of the aetiology and prevalence of NDEBID, enumerate common problems associated with current classification systems and provide recommendations for a more integrated approach to the nosology and clinical care of these related conditions.

The impact of Covid-19 pandemic on services for children and adolescents with ADHD: results from a survey of paediatricians in the United Kingdom.

Background: The Covid-19 pandemic has led to huge disruptions and multi-domain healthcare crisis, with additional impact on children and young people (CYP) affected by Attention Deficit and Hyperactivity Disorder (ADHD). Methods: We conducted an online survey and obtained responses from 62 Paediatricians who provide ADHD services for CYP about their experience of Service disruption and adaptations during the first Covid-19 lockdown in the United Kingdom between March and June 2020. The responses were both quantitative and qualitative. Results: The Paediatricians reported huge service disruptions such that almost half ceased the assessment of new patients with ADHD, and only 5% were able to offer physical monitoring for most patients. However, all respondents had adopted telemedicine, which allowed them to maintain high levels of non-physical service provision for existing patients. The Paediatricians used risk stratification strategies to determine which patients were more likely to benefit from the limited available face to face appointments for physical monitoring. The Paediatricians demonstrated clinical pragmatism to meet the needs of their patients such as starting medication without physical exam especially if the patient's behaviour was so challenging that it was presenting a crisis at home, and setting aside monthly limits for stimulant medications. Some respondents reported helpful cross-service collaborations to support CYP with ADHD and their families. Conclusion: The Covid-19 pandemic has had adverse effect on many CYP with ADHD and caused huge disruption to the ADHD services that support them. As the pandemic continues to cause disruptions to ADHD services, the service adaptations emerging from the literature including some of those identified in this study could be useful to support more stable and sustainable ADHD services, both during and after the pandemic.

Community paediatricians' experience of joint working with child and adolescent mental health services: findings from a British national survey.

OBJECTIVES: Children and young people (CYP) presenting to paediatric or child and adolescent mental health services (CAMHS) often have needs spanning medical and psychiatric diagnoses. However, joint working between paediatrics and CAMHS remains limited. We surveyed community paediatricians in the UK to inform better strategies to improve joint working with CAMHS. METHODS: We conducted an online survey of community paediatricians through the British Association for Community Child Health (BACCH) on how much joint working they experienced with CAMHS, any hindrances to more collaborative working, and the impact on service users and service provision. This paper is based on thematic analysis of 327 free-text comments by paediatricians. RESULTS: A total of 245 community paediatricians responded to the survey (22% of BACCH members). However, some responses were made on behalf of teams rather than for individual paediatricians. The following were the key themes identified: a strong support for joint working between community paediatrics and CAMHS; an acknowledgement that current levels of joint working were limited; the main barriers to joint working were splintered commissioning and service structures (eg, where integrated care systems fund different providers to meet overlapping children's health needs); and the most commonly reported negative impact of non-joint working was severely limited access to CAMHS for CYP judged by paediatricians to require mental health support, particularly those with autism spectrum disorder. CONCLUSION: There is very limited joint working between community paediatrics and CAMHS in the UK, which is associated with many adverse impacts on service users and providers. A prointegration strategy that includes joint commissioning of adequately funded paediatric and CAMHS services that are colocated and within the same health management organisations is crucial to improving joint working between paediatrics and CAMHS.

Involvement of community paediatricians in the care of children and young people with mental health difficulties in the UK: implications for case ascertainment by child and adolescent psychiatric, and paediatric surveillance systems.

Objective: To ascertain the extent to which community paediatricians are involved in the care of children with mental health conditions in order to determine which difficulties are appropriate for single or joint surveillance by the British Paediatric Surveillance Unit (BPSU) and Child and Adolescent Psychiatry Surveillance System (CAPSS). Design: An online survey of the 1120 members of the British Association of Community Child Health (BACCH) working in 169 Community Child Health (CCH) services in the UK. Results: A total of 245 community paediatricians responded to the survey. This represents 22% of members of BACCH but likely to have covered many of the 169 CCH units because participants could respond on behalf of other members in their unit. The survey showed that children and young people (CYP) with neurodevelopmental conditions presented more frequently to paediatrics than to Child and Adolescent Mental Health Services (CAMHS). In addition, a sizeable proportion of CYP with emotional difficulties presented to paediatricians (eg, 29.5% for anxiety/obsessive compulsive disorder (OCD), and 12.8% for depression)-mainly due to difficulty with accessing CAMHS. More than half of the community paediatricians are involved in the care of CYP with anxiety and OCD, while 32.3% are involved in the care of those with depression. Conclusion: There is significant involvement of community paediatricians in the care of CYP with mental health conditions. Involvement is highest for neurodevelopmental conditions, but also significant for CYP with emotional difficulties. The implication of the findings for surveillance case ascertainment is that joint BPSU and CAPSS is recommended for surveillance studies of neurodevelopmental conditions. However, for emotional disorders, single or joint surveillance should be made based on the specific research question and the relative trade-offs between case ascertainment, and the additional cost and reporting burden of joint surveillance. Single CAPSS studies remain appropriate for psychosis and bipolar disorder.

Validation of Chemokine Biomarkers in Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive muscle disease involving complex skeletal muscle pathogenesis. The pathogenesis is triggered by sarcolemma instability due to the lack of dystrophin protein expression, leading to Ca2+ influx, muscle fiber apoptosis, inflammation, muscle necrosis, and fibrosis. Our lab recently used two high-throughput multiplexing techniques (e.g., SomaScan® aptamer assay and tandem mass tag-(TMT) approach) and identified a series of serum protein biomarkers tied to different pathobiochemical pathways. In this study, we focused on validating the circulating levels of three proinflammatory chemokines (CCL2, CXCL10, and CCL18) that are believed to be involved in an early stage of muscle pathogenesis. We used highly specific and reproducible MSD ELISA assays and examined the association of these chemokines with DMD pathogenesis, age, disease severity, and response to glucocorticoid treatment. As expected, we confirmed that these three chemokines were significantly elevated in serum and muscle samples of DMD patients relative to age-matched healthy controls (p-value < 0.05, CCL18 was not significantly altered in muscle samples). These three chemokines were not significantly elevated in Becker muscular dystrophy (BMD) patients, a milder form of dystrophinopathy, when compared in a one-way ANOVA to a control group but remained significantly elevated in the age-matched DMD group (p < 0.05). CCL2 and CCL18 but not CXCL10 declined with age in DMD patients, whereas all three chemokines remained unchanged with age in BMD and controls. Only CCL2 showed significant association with time to climb four steps in the DMD group (r = 0.48, p = 0.038) and neared significant association with patients' reported outcome in the BMD group (r = 0.39, p = 0.058). Furthermore, CCL2 was found to be elevated in a serum of the mdx mouse model of DMD, relative to wild-type mouse model. This study suggests that CCL2 might be a suitable candidate biomarker for follow-up studies to demonstrate its physiological significance and clinical utility in DMD.

Tandem Mass Tag-Based Serum Proteome Profiling for Biomarker Discovery in Young Duchenne Muscular Dystrophy Boys.

Blood-accessible molecular biomarkers are becoming highly attractive tools to assess disease progression and response to therapies in Duchenne muscular dystrophy (DMD) especially in very young patients for whom other outcome measures remain subjective and challenging. In this study, we have standardized a highly specific and reproducible multiplexing mass spectrometry method using the tandem mass tag (TMT) strategy in combination with depletion of abundant proteins from serum and high-pH reversed-phase peptide fractionation. Differential proteome profiling of 4 year-old DMD boys (n = 9) and age-matched healthy controls (n = 9) identified 38 elevated and 50 decreased serum proteins (adjusted P < 0.05, FDR <0.05) in the DMD group relative to the healthy control group. As expected, we confirmed previously reported biomarkers but also identified novel biomarkers. These included novel muscle injury-associated biomarkers such as telethonin, smoothelin-like protein 1, cofilin-1, and plectin, additional muscle-specific enzymes such as UTP-glucose-1-phosphate uridylyltransferase, aspartate aminotransferase, pyruvate kinase PKM, lactotransferrin, tissue alpha-l-fucosidase, pantetheinase, and ficolin-1, and some pro-inflammatory and cell adhesion-associated biomarkers such as leukosialin, macrophage receptor MARCO, vitronectin, galectin-3-binding protein, and ProSAAS. The workflow including serum depletion, sample processing, and mass spectrometry analysis was found to be reproducible and stable over time with CV < 20%. Furthermore, the method was found to be superior in terms of specificity compared to other multiplexing affinity-based methods. These findings demonstrate the specificity and reliability of TMT-based mass spectrometry methods in detection and identification of serum biomarkers in presymptomatic young DMD patients.

Disease-specific and glucocorticoid-responsive serum biomarkers for Duchenne Muscular Dystrophy.

Extensive biomarker discoveries for DMD have occurred in the past 7 years, and a vast array of these biomarkers were confirmed in independent cohorts and across different laboratories. In these previous studies, glucocorticoids and age were two major confounding variables. In this new study, using SomaScan technology and focusing on a subset of young DMD patients who were not yet treated with glucocorticoids, we identified 108 elevated and 70 decreased proteins in DMD relative to age matched healthy controls (p value < 0.05 after adjusting for multiple testing). The majority of the elevated proteins were muscle centric followed by cell adhesion, extracellular matrix proteins and a few pro-inflammatory proteins. The majority of decreased proteins were of cell adhesion, however, some had to do with cell differentiation and growth factors. Subsequent treatment of this group of DMD patients with glucocorticoids affected two major groups of pharmacodynamic biomarkers. The first group consisted of 80 serum proteins that were not associated with DMD and either decreased or increased following treatment with glucocorticoids, and therefore were reflective of a broader effect of glucocorticoids. The second group consisted of 17 serum proteins that were associated with DMD and these tended to normalize under treatment, thus reflecting physiologic effects of glucocorticoid treatment in DMD. In summary, we have identified a variety of circulating protein biomarkers that reflect the complex nature of DMD pathogenesis and response to glucocorticoids.

Behavioural and emotional disorders in childhood: A brief overview for paediatricians.

Mental health problems in children and adolescents include several types of emotional and behavioural disorders, including disruptive, depression, anxiety and pervasive developmental (autism) disorders, characterized as either internalizing or externalizing problems. Disruptive behavioural problems such as temper tantrums, attention deficit hyperactivity disorder, oppositional, defiant or conduct disorders are the commonest behavioural problems in preschool and school age children. The routine Paediatric clinic or Family Medicine/General Practitioner surgery presents with several desirable characteristics that make them ideal for providing effective mental health services to children and adolescents. DSM-5 and ICD-10 are the universally accepted standard criteria for the classification of mental and behaviour disorders in childhood and adults. The age and gender prevalence estimation of various childhood behavioural disorders are variable and difficult to compare worldwide. A review of relevant published literature was conducted, including published meta-analyses and national guidelines. We searched for articles indexed by Ovid, PubMed, PubMed Medical Central, CINAHL, EMBASE, Database of Abstracts and Reviews, and the Cochrane Database of Systematic reviews and other online sources. The searches were conducted using a combination of search expressions including "childhood", "behaviour", "disorders" or "problems". Childhood behaviour and emotional problems with their related disorders have significant negative impacts on the individual, the family and the society. They are commonly associated with poor academic, occupational, and psychosocial functioning. It is important for all healthcare professionals, especially the Paediatricians to be aware of the range of presentation, prevention and management of the common mental health problems in children and adolescents.

Review of the evidence for the management of co-morbid Tic disorders in children and adolescents with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children and adolescents, with prevalence ranging between 5% and 12% in the developed countries. Tic disorders (TD) are common co-morbidities in paediatric ADHD patients with or without pharmacotherapy treatment. There has been conflicting evidence of the role of psychostimulants in either precipitating or exacerbating TDs in ADHD patients. We carried out a literature review relating to the management of TDs in children and adolescents with ADHD through a comprehensive search of MEDLINE, EMBASE, CINAHL and Cochrane databases. No quantitative synthesis (meta-analysis) was deemed appropriate. Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and normal doses of psychostimulant use. Supratherapeutic doses of dextroamphetamine have been shown to exacerbate TD. Most tics are mild or moderate and respond to psychoeducation and behavioural management. Level A evidence support the use of alpha adrenergic agonists, including Clonidine and Guanfacine, reuptake noradrenenaline inhibitors (Atomoxetine) and stimulants (Methylphenidate and Dexamphetamines) for the treatment of Tics and comorbid ADHD. Priority should be given to the management of co-morbid Tourette's syndrome (TS) or severely disabling tics in children and adolescents with ADHD. Severe TDs may require antipsychotic treatment. Antipsychotics, especially Aripiprazole, are safe and effective treatment for TS or severe Tics, but they only moderately control the co-occurring ADHD symptomatology. Short vignettes of different common clinical scenarios are presented to help clinicians determine the most appropriate treatment to consider in each patient presenting with ADHD and co-morbid TDs.

Effects of storage on the physicochemical and antibacterial properties of human milk.

Storage of human milk for limited periods of time is unavoidable in neonatal units and also in the home where increasing numbers of mothers go back to work soon after delivery. Many mothers, convinced of the importance of prolonged exclusive or complementary breast-feeding, often express and store human milk for use during the period of separation. This study examines the effects of different storage methods on the pH and some antibacterial activities of human milk. Portions of milk and colostrum samples from healthy lactating mothers were stored at 4 degrees C and -20 degrees C for periods ranging from one day to 12 weeks. The stored milk samples were analysed for pH, bactericidal and bacteria sequestration activities against a serum-sensitive Escherichia coli, and compared with freshly collected samples, with and without EDTA. Milk became progressively more acidic during storage. While the bactericidal activities of refrigerated samples diminished rapidly, up to two-thirds of the original activity level was maintained by freezing for up to three months. The ability of milk fat globule membrane to adhere to suspended bacteria was gradually lost in frozen milk samples, while it was greatly enhanced during the first few days in refrigerated samples, before declining sharply. This study shows that loss of bactericidal activity in refrigerated milk is well compensated for by enhanced bacteria sequestration activity, and allays any fears that might arise concerning the suitability of stored human milk for infant consumption.

When should we be conducting thyroid function tests in newborns and young infants?

An audit of local practice was undertaken as regards requests for thyroid function tests (TFT) in children aged between birth and 3 months at two local hospitals in South West England between 2005 and 2008. A total of 406 tests were performed (2.6 tests per week) over a 2-year period at a teaching hospital (70 tests per 1000 live births yearly), with 233 tests (1.5 tests per week) performed over a 3-year period at a local district hospital (39 tests per 1000 live births yearly). The highest proportion of all the tests was performed as routine investigation of prolonged neonatal jaundice (64% and 55%, respectively). Other common indications were maternal thyroid disorders (5.4% vs 4.7%) and suspected neonatal thyroid disorders (3% vs 9%). There was no confirmed diagnosis of infantile thyroid disease. Available evidence and this audit suggest that too many thyroid function tests are unnecessarily performed in young infants.