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1.  Paediatric clinical pharmacology in the UK 
Archives of Disease in Childhood  2014;99(12):1143-1146.
Paediatric clinical pharmacology is the scientific study of medicines in children and is a relatively new subspecialty in paediatrics in the UK. Training encompasses both the study of the effectiveness of drugs in children (clinical trials) and aspects of drug toxicity (pharmacovigilance). Ethical issues in relation to clinical trials and also studies of the pharmacokinetics and drug metabolism in children are crucial. Paediatric patients require formulations that young children in particular are able to take. The scientific evidence generated from clinical trials, pharmacokinetic studies and studies of drug toxicity all need to be applied in order to ensure that medicines are used rationally in children.
PMCID: PMC4251165  PMID: 25202131
Pharmacology; Toxicology; Evidence Based Medicine
2.  Marketing breast milk substitutes: problems and perils throughout the world 
Archives of Disease in Childhood  2012;97(6):529-532.
On 21 May 1981 the WHO International Code of Marketing Breast Milk Substitutes (hereafter referred to as the Code) was passed by 118 votes to 1, the US casting the sole negative vote. The Code arose out of concern that the dramatic increase in mortality, malnutrition and diarrhoea in very young infants in the developing world was associated with aggressive marketing of formula. The Code prohibited any advertising of baby formula, bottles or teats and gifts to mothers or ‘bribery’ of health workers. Despite successes, it has been weakened over the years by the seemingly inexhaustible resources of the global pharmaceutical industry. This article reviews the long and tortuous history of the Code through the Convention on the Rights of the Child, the HIV pandemic and the rare instances when substitute feeding is clearly essential. Currently, suboptimal breastfeeding is associated with over a million deaths each year and 10% of the global disease burden in children. All health workers need to recognise inappropriate advertising of formula, to report violations of the Code and to support efforts to promote breastfeeding: the most effective way of preventing child mortality throughout the world.
PMCID: PMC3371222  PMID: 22419779
3.  Management of Crohn's disease 
Archives of Disease in Childhood  2015;101(5):475-480.
Crohn's disease (CD) is rapidly increasing in children so an up to date knowledge of diagnosis, investigation and management is essential. Exclusive enteral nutrition is the first line treatment for active disease. The vast majority of children will need immunosuppressant treatment and around 20% will need treatment with biologics. Recent guidelines have helped make best use of available therapies.
PMCID: PMC4853609  PMID: 26553907
Gastroenterology; Therapeutics
4.  What clinical signs best identify severe illness in young infants aged 0–59 days in developing countries? A systematic review 
Archives of disease in childhood  2011;96(11):1052-1059.
Despite recent overall improvement in the survival of under-five children worldwide, mortality among young infants remains high, and accounts for an increasing proportion of child deaths in resource-poor settings. In such settings, clinical decisions for appropriate management of severely ill infants have to be made on the basis of presenting clinical signs, and with limited or no laboratory facilities. This review summarises the evidence from observational studies of clinical signs of severe illnesses in young infants aged 0–59 days, with a particular focus on defining a minimum set of best predictors of the need for hospital-level care. Available moderate to high quality evidence suggests that, among sick infants aged 0–59 days brought to a health facility, the following clinical signs—alone or in combination—are likely to be the most valuable in identifying infants at risk of severe illness warranting hospital-level care: history of feeding difficulty, history of convulsions, temperature (axillary) ≥37.5°C or <35.5°C, change in level of activity, fast breathing/respiratory rate ≥60 breaths per minute, severe chest indrawing, grunting and cyanosis.
PMCID: PMC3081806  PMID: 21220263
5.  Common visual problems in children with disability 
Archives of Disease in Childhood  2014;99(12):1163-1168.
Children with disability are at a substantially higher risk of visual impairment (VI) (10.5% compared with 0.16%) but also of ocular disorders of all types, including refractive errors and strabismus. The aetiology of VI in children with disability reflects that of the general population and includes cerebral VI, optic atrophy, as well as primary visual disorders such as retinal dystrophies and structural eye anomalies. VI and other potentially correctable ocular disorders may not be recognised without careful assessment and are frequently unidentified in children with complex needs. Although assessment may be more challenging than in other children, identifying these potential additional barriers to learning and development may be critical. There is a need to develop clearer guidelines, referral pathways and closer working between all professionals involved in the care of children with disability and visual disorders to improve our focus on the assessment of vision and outcomes for children with disability.
PMCID: PMC4251159  PMID: 25165073
Neurodisability; Ophthalmology; Paediatric Practice
6.  Management of ulcerative colitis 
Archives of Disease in Childhood  2015;101(5):469-474.
Ulcerative colitis (UC) in children is increasing. The range of treatments available has also increased too but around 1 in 4 children still require surgery to control their disease. An up-to-date understanding of treatments is essential for all clinicians involved in the care of UC patients to ensure appropriate and timely treatment while minimising the risk of complications and side effects.
PMCID: PMC4853583  PMID: 26553909
Gastroenterology; Multidisciplinary team-care; Paediatric Surgery
7.  Armed conflict and child health 
Armed conflict has a major impact on child health throughout the world. One in six children worldwide lives in an area of armed conflict and civilians are more likely to die than soldiers as a result of the conflict. In stark contrast to the effect on children, the international arms trade results in huge profits for the large corporations involved in producing arms, weapons and munitions. Armed conflict is not inevitable but is an important health issue that should be prevented.
PMCID: PMC3237260  PMID: 21393303
8.  Poverty and child health in the UK: using evidence for action 
Archives of Disease in Childhood  2016;101(8):759-766.
There are currently high levels of child poverty in the UK, and for the first time in almost two decades child poverty has started to rise in absolute terms. Child poverty is associated with a wide range of health-damaging impacts, negative educational outcomes and adverse long-term social and psychological outcomes. The poor health associated with child poverty limits children's potential and development, leading to poor health and life chances in adulthood. This article outlines some key definitions with regard to child poverty, reviews the links between child poverty and a range of health, developmental, behavioural and social outcomes for children, describes gaps in the evidence base and provides an overview of current policies relevant to child poverty in the UK. Finally, the article outlines how child health professionals can take action by (1) supporting policies to reduce child poverty, (2) providing services that reduce the health consequences of child poverty and (3) measuring and understanding the problem and assessing the impact of action.
PMCID: PMC4975805  PMID: 26857824
Children's Rights; Child poverty; Health inequalities; Child health professionals
9.  Safe and effective pharmacotherapy in infants and preschool children: importance of formulation aspects 
Archives of Disease in Childhood  2016;101(7):662-669.
Safe and effective paediatric pharmacotherapy requires careful evaluation of the type of drug substance, the necessary dose and the age-appropriateness of the formulation. Generally, the younger the child, the more the attention that is required. For decades, there has been a general lack of (authorised) formulations that children are able to and willing to take. Moreover, little was known on the impact of pharmaceutical aspects on the age-appropriateness of a paediatric medicine. As a result of legislative incentives, such knowledge is increasingly becoming available. It has become evident that rapidly dissolving tablets with a diameter of 2 mm (mini-tablets) can be used in preterm neonates and non-rapidly dissolving 2 mm mini-tablets in infants from 6 months of age. In addition, uncoated 4 mm mini-tablets can be used in infants from the age of 1 year. Also, there is some evidence that children prefer mini-tablets over a powder, suspension or syrup. Other novel types of age-appropriate oral formulations such as orodispersible films may further add to the treatment possibilities. This review provides an overview of the current knowledge on oral formulations for infants and preschool children, the advantages and disadvantages of the different types of dosage forms and the age groups by which these can likely be used.
PMCID: PMC4941170  PMID: 26979250
child; tehnology, pharmaceutical; formulation; mini-tablet; administration, oral
10.  Enter B and W: two new meningococcal vaccine programmes launched 
Archives of Disease in Childhood  2016;101(1):91-95.
In 2015, the UK became the first country in the world to have a comprehensive routine meningococcal vaccine programme targeting all of the main capsular groups of N. meningitidis. 1 An infant vaccine programme against meningococcal capsular group B Neisseria meningitidis (MenB) was launched from 1st September with an aim to reduce endemic MenB disease in early childhood. On 1st August 2015, an adolescent programme against groups A, C, W and Y meningococci (MenACWY) was rolled out to halt a growing outbreak of capsular group W disease (MenW) caused by a hypervirulent clone of N. meningitidis, in addition to maintaining control against MenC disease provided by the current adolescent programme. 2
PMCID: PMC4717420  PMID: 26672098
Infectious Diseases; Immunisation
11.  Long-term effects of bullying 
Archives of Disease in Childhood  2015;100(9):879-885.
Bullying is the systematic abuse of power and is defined as aggressive behaviour or intentional harm-doing by peers that is carried out repeatedly and involves an imbalance of power. Being bullied is still often wrongly considered as a ‘normal rite of passage’. This review considers the importance of bullying as a major risk factor for poor physical and mental health and reduced adaptation to adult roles including forming lasting relationships, integrating into work and being economically independent. Bullying by peers has been mostly ignored by health professionals but should be considered as a significant risk factor and safeguarding issue.
PMCID: PMC4552909  PMID: 25670406
Child Abuse; Psychology; School Health; General Paediatrics; Outcomes research
12.  Optimal management of allergic rhinitis 
Archives of Disease in Childhood  2015;100(6):576-582.
Allergic rhinitis (AR), the most common chronic disease in childhood is often ignored, misdiagnosed and/or mistreated. Undertreated AR impairs quality of life, exacerbates asthma and is a major factor in asthma development. It can involve the nose itself, as well as the organs connected with the nose manifesting a variety of symptoms. Evidence-based guidelines for AR therapy improve disease control. Recently, paediatric AR guidelines have been published by the European Academy of Allergy and Clinical Immunology and are available online, as are a patient care pathway for children with AR and asthma from the Royal College of Paediatrics and Child Health. Management involves diagnosis, followed by avoidance of relevant allergens, with additional pharmacotherapy needed for most sufferers. This ranges, according to severity, from saline sprays, through non-sedating antihistamines, oral or topical, with minimally bioavailable intranasal corticosteroids for moderate/severe disease, possibly plus additional antihistamine or antileukotriene. The concept of rhinitis control is emerging, but there is no universally accepted definition. Where pharmacotherapy fails, allergen-specific immunotherapy, which is uniquely able to alter long-term disease outcomes, should be considered. The subcutaneous form (subcutaneous immunotherapy) in children has been underused because of concerns regarding safety and acceptability of injections. Sublingual immunotherapy is both efficacious and safe for grass pollen allergy. Further studies on other allergens in children are needed. Patient, carer and practitioner education into AR and its treatment are a vital part of management.
PMCID: PMC4514979  PMID: 25838332
Allergy; Cystic Fibrosis; Evidence Based Medicine; General Paediatrics; Paediatric Practice
13.  Obsessive-compulsive disorder in children and adolescents 
Archives of Disease in Childhood  2014;100(5):495-499.
Obsessive-compulsive disorder (OCD) in childhood and adolescence is an impairing condition, associated with a specific set of distressing symptoms incorporating repetitive, intrusive thoughts (obsessions) and distressing, time-consuming rituals (compulsions). This review considers current knowledge of causes and mechanisms underlying OCD, as well as assessment and treatment. Issues relating to differential diagnosis are summarised, including the challenges of distinguishing OCD from autism spectrum disorders and tic disorders in youth. The recommended treatments, namely cognitive behaviour therapy and serotonin reuptake inhibiting/selective serotonin reuptake inhibitor medications, are outlined along with the existing evidence-based and factors associated with treatment resistance. Finally, novel clinical developments that are emerging in the field and future directions for research are discussed.
PMCID: PMC4413836  PMID: 25398447
Child Psychiatry; Child Psychology; Psychology; Outcomes research
14.  Antiepileptic drug treatment of rolandic epilepsy and Panayiotopoulos syndrome: clinical practice survey and clinical trial feasibility 
Archives of Disease in Childhood  2014;100(1):62-67.
The evidence base for management of childhood epilepsy is poor, especially for the most common specific syndromes such as rolandic epilepsy (RE) and Panayiotopoulos syndrome (PS). Considerable international variation in management and controversy about non-treatment indicate the need for high quality randomised controlled trials (RCT). The aim of this study is, therefore, to describe current UK practice and explore the feasibility of different RCT designs for RE and PS.
We conducted an online survey of 590 UK paediatricians who treat epilepsy. Thirty-two questions covered annual caseload, investigation and management practice, factors influencing treatment, antiepileptic drug preferences and hypothetical trial design preferences.
132 responded (22%): 81% were paediatricians and 95% at consultant seniority. We estimated, annually, 751 new RE cases and 233 PS cases. Electroencephalography (EEG) is requested at least half the time in approximately 70% of cases; MRI brain at least half the time in 40%–65% cases and neuropsychological evaluation in 7%–8%. Clinicians reported non-treatment in 40%: main reasons were low frequency of seizures and parent/child preferences. Carbamazepine is the preferred older, and levetiracetam the preferred newer, RCT arm. Approximately one-half considered active and placebo designs acceptable, choosing seizures as primary and cognitive/behavioural measures as secondary outcomes.
Management among respondents is broadly in line with national guidance, although with possible overuse of brain imaging and underuse of EEG and neuropsychological assessments. A large proportion of patients in the UK remains untreated, and clinicians seem amenable to a range of RCT designs, with carbamazepine and levetiracetam the preferred active drugs.
PMCID: PMC4283698  PMID: 25202134
Neurology; Paediatric Practice
15.  Evidence review of hydroxyurea for the prevention of sickle cell complications in low-income countries 
Archives of Disease in Childhood  2013;98(11):908-914.
Hydroxyurea is widely used in high-income countries for the management of sickle cell disease (SCD) in children. In Kenyan clinical guidelines, hydroxyurea is only recommended for adults with SCD. Yet many deaths from SCD occur in early childhood, deaths that might be prevented by an effective, disease modifying intervention. The aim of this review was to summarise the available evidence on the efficacy, effectiveness and safety of hydroxyurea in the management of SCD in children below 5 years of age to support guideline development in Kenya. We undertook a systematic review and used the Grading of Recommendations Assessment, Development and Evaluation system to appraise the quality of identified evidence. Overall, available evidence from 1 systematic review (n=26 studies), 2 randomised controlled trials (n=354 children), 14 observational studies and 2 National Institute of Health reports suggest that hydroxyurea may be associated with improved fetal haemoglobin levels, reduced rates of hospitalisation, reduced episodes of acute chest syndrome and decreased frequency of pain events in children with SCD. However, it is associated with adverse events (eg, neutropenia) when high to maximum tolerated doses are used. Evidence is lacking on whether hydroxyurea improves survival if given to young children. Majority of the included studies were of low quality and mainly from high-income countries. Overall, available limited evidence suggests that hydroxyurea may improve morbidity and haematological outcomes in SCD in children aged below 5 years and appears safe in settings able to provide consistent haematological monitoring.
PMCID: PMC3812872  PMID: 23995076
Genetics; Haematology
16.  Hurricanes and child health: lessons from Cuba 
Archives of Disease in Childhood  2010;96(4):328-329.
PMCID: PMC3056292  PMID: 20861403
17.  Assessment and management of anxiety disorders in children and adolescents 
Archives of Disease in Childhood  2014;99(7):674-678.
Anxiety disorders in childhood and adolescence are extremely common and are often associated with lifelong psychiatric disturbance. Consistent with DSM-5 and the extant literature, this review concerns the assessment and treatment of specific phobias, separation anxiety disorder, generalised anxiety disorder, social anxiety disorder, panic disorder and agoraphobia. Evidence-based psychological treatments (cognitive behaviour therapy; CBT) for these disorders have been developed and investigated, and in recent years promising low-intensity versions of CBT interventions have been proposed that offer a means to increase access to evidence-based treatments. There is some evidence of effectiveness of pharmacological treatments for anxiety disorders in children and young people, however, routine prescription is not recommended due to concerns about potential harm.
PMCID: PMC4078705  PMID: 24636957
Anxiety; Assessment; Treatment; Children; Adolescents
18.  Diagnosis and management of primary ciliary dyskinesia 
Archives of Disease in Childhood  2014;99(9):850-856.
Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder of motile cilia characterised by chronic lung disease, rhinosinusitis, hearing impairment and subfertility. Nasal symptoms and respiratory distress usually start soon after birth, and by adulthood bronchiectasis is invariable. Organ laterality defects, usually situs inversus, occur in ∼50% of cases. The estimated prevalence of PCD is up to ∼1 per 10 000 births, but it is more common in populations where consanguinity is common. This review examines who to refer for diagnostic testing. It describes the limitations surrounding diagnosis using currently available techniques and considers whether recent advances to genotype patients with PCD will lead to genetic testing and screening to aid diagnosis in the near future. It discusses the challenges of monitoring and treating respiratory and ENT disease in children with PCD.
PMCID: PMC4145427  PMID: 24771309
primary ciliary dyskinesia; Kartagener syndrome; treatment; diagnosis; ciliary motility disorders
19.  Prospects for eradication of meningococcal disease 
Archives of Disease in Childhood  2012;97(11):993-998.
Meningococcal meningitis and septicaemia remain a serious global health threat. This review focuses on the epidemiology of meningococcal disease following the recent implementation of effective vaccines and the potential utility of a vaccine against serogroup B meningococcus.
PMCID: PMC3512348  PMID: 22984187
Epidemiology; Intensive Care; Mortality; Infectious Diseases
20.  Drug treatment of inborn errors of metabolism: a systematic review 
Archives of Disease in Childhood  2013;98(6):454-461.
The treatment of inborn errors of metabolism (IEM) has seen significant advances over the last decade. Many medicines have been developed and the survival rates of some patients with IEM have improved. Dosages of drugs used for the treatment of various IEM can be obtained from a range of sources but tend to vary among these sources. Moreover, the published dosages are not usually supported by the level of existing evidence, and they are commonly based on personal experience.
A literature search was conducted to identify key material published in English in relation to the dosages of medicines used for specific IEM. Textbooks, peer reviewed articles, papers and other journal items were identified. The PubMed and Embase databases were searched for material published since 1947 and 1974, respectively. The medications found and their respective dosages were graded according to their level of evidence, using the grading system of the Oxford Centre for Evidence-Based Medicine.
83 medicines used in various IEM were identified. The dosages of 17 medications (21%) had grade 1 level of evidence, 61 (74%) had grade 4, two medications were in level 2 and 3 respectively, and three had grade 5.
To the best of our knowledge, this is the first review to address this matter and the authors hope that it will serve as a quickly accessible reference for medications used in this important clinical field.
PMCID: PMC3693126  PMID: 23532493
Inborn errors of metabolism; IEM; evidence based medicine; treatment; dosage
21.  Management of Kawasaki disease 
Kawasaki disease (KD) is an acute self-limiting inflammatory disorder, associated with vasculitis, affecting predominantly medium-sized arteries, particularly the coronary arteries. In developed countries KD is the commonest cause of acquired heart disease in childhood. The aetiology of KD remains unknown, and it is currently believed that one or more as yet unidentified infectious agents induce an intense inflammatory host response in genetically susceptible individuals. Genetic studies have identified several susceptibility genes for KD and its sequelae in different ethnic populations, including FCGR2A, CD40, ITPKC, FAM167A-BLK and CASP3, as well as genes influencing response to intravenous immunoglobulin (IVIG) and aneurysm formation such as FCGR3B, and transforming growth factor (TGF) β pathway genes. IVIG and aspirin are effective therapeutically, but recent clinical trials and meta-analyses have demonstrated that the addition of corticosteroids to IVIG is beneficial for the prevention of coronary artery aneurysms (CAA) in severe cases with highest risk of IVIG resistance. Outside of Japan, however, clinical scores to predict IVIG resistance perform suboptimally. Furthermore, the evidence base does not provide clear guidance on which corticosteroid regimen is most effective. Other therapies, including anti-TNFα, could also have a role for IVIG-resistant KD. Irrespective of these caveats, it is clear that therapy that reduces inflammation in acute KD, improves outcome. This paper summarises recent advances in the understanding of KD pathogenesis and therapeutics, and provides an approach for managing KD patients in the UK in the light of these advances.
PMCID: PMC3888612  PMID: 24162006
Infectious Diseases; Rheumatology
22.  What causes attention deficit hyperactivity disorder? 
Archives of Disease in Childhood  2011;97(3):260-265.
Attention deficit hyperactivity disorder (ADHD) affects around 1–3% of children. There is a high level of comorbidity with developmental and learning problems as well as with a variety of psychiatric disorders. ADHD is highly heritable, although there is no single causal risk factor and non-inherited factors also contribute to its aetiology. The genetic and environmental risk factors that have been implicated appear to be associated with a range of neurodevelopmental and neuropsychiatric outcomes, not just ADHD. The evidence to date suggests that both rare and multiple common genetic variants likely contribute to ADHD and modify its phenotype. ADHD or a similar phenotype also appears to be more common in extreme low birth weight and premature children and those exposed to exceptional early adversity. In this review, the authors consider recent developments in the understanding of risk factors that influence ADHD.
PMCID: PMC3927422  PMID: 21903599
23.  What clinical signs best identify severe illness in young infants aged 0–59 days in developing countries? A systematic review 
Archives of Disease in Childhood  2011;96(11):1052-1059.
Despite recent overall improvement in the survival of under-five children worldwide, mortality among young infants remains high, and accounts for an increasing proportion of child deaths in resource-poor settings. In such settings, clinical decisions for appropriate management of severely ill infants have to be made on the basis of presenting clinical signs, and with limited or no laboratory facilities. This review summarises the evidence from observational studies of clinical signs of severe illnesses in young infants aged 0–59 days, with a particular focus on defining a minimum set of best predictors of the need for hospital-level care. Available moderate to high quality evidence suggests that, among sick infants aged 0–59 days brought to a health facility, the following clinical signs—alone or in combination—are likely to be the most valuable in identifying infants at risk of severe illness warranting hospital-level care: history of feeding difficulty, history of convulsions, temperature (axillary) ≥37.5°C or <35.5°C, change in level of activity, fast breathing/respiratory rate ≥60 breaths per minute, severe chest indrawing, grunting and cyanosis.
PMCID: PMC3081806  PMID: 21220263

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