Most doctors can identify key papers that have influenced their approach to the management of a particular clinical problem, although sometimes the gestation period of this effect can be very prolonged. In this short review I discuss the effects of a seminal paper by Sheila Mackenzie from the early 1990s on my current approach to the diagnosis and management of chronic cough in children.
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.
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.
Inborn errors of metabolism; IEM; evidence based medicine; treatment; dosage
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.
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.
Infectious Diseases; Rheumatology
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.
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.
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.
Epidemiology; Intensive Care; Mortality; Infectious Diseases
A torn labial frenum is widely regarded as pathognomonic of abuse.
We systematically reviewed the evidence for this, and to define other intra‐oral injuries found in physical abuse. Nine studies documented abusive torn labial frena in 30 children and 27 were fatally abused: 22 were less than 5 years old. Only a direct blow to the face was substantiated as a mechanism of injury.
Two studies noted accidentally torn labial frena, both from intubation. Abusive intra‐oral injuries were widely distributed to the lips, gums, tongue and palate and included fractures, intrusion and extraction of the dentition, bites and contusions.
Current literature does not support the diagnosis of abuse based on a torn labial frenum in isolation. The intra‐oral hard and soft tissue should be examined in all suspected abuse cases, and a dental opinion sought where abnormalities are found.
abuse; frenum; intra‐oral injury; torn labial frenum; systematic review
Primary ciliary dyskinesia (PCD) is usually inherited as an autosomal recessive disorder and presents with upper and lower respiratory tract infection, and mirror image arrangement in around 50% of cases. Cilia dysfunction is also implicated in a wider spectrum of disease, including polycystic liver and kidney disease, central nervous system problems including retinopathy and hydrocephalus, and biliary atresia. Cilia are complex structures, containing more than 250 proteins; recent studies have begun to locate PCD genes scattered throughout the genome. Screening tests for PCD include nasal nitric oxide and in vivo tests of ciliary motility such as the saccharin test. Specific diagnosis requires examination of cilia by light and electron microscopy, with epithelial culture in doubtful cases. This is only available in supra‐regional centres, recently centrally funded by the National Commissioning Group. Treatment is not evidence based and recommendations are largely extrapolated from cystic fibrosis and other suppurative lung diseases.
Facial appearance can be a significant clue in the initial identification of genetic conditions, but their low incidence limits exposure during training and inhibits the development of skills in recognising the facial “gestalt” characteristic of many dysmorphic syndromes. Here we describe the potential of computer‐based models of three‐dimensional (3D) facial morphology to assist in dysmorphology training, in clinical diagnosis and in multidisciplinary studies of phenotype–genotype correlations.
facial dysmorphology; 3D shape models
The harmful effects of ionising radiation are widely acknowledged. It has been reported that young children, particularly girls, have a higher sensitivity to radiation than adults. However, the exact detrimental effects of radiation, particularly at the low doses used in routine diagnostic radiography, are unknown and the subject of much controversy. Computed tomography (CT) accounts for about 9% of all radiological examinations but is responsible for 47% of medical radiation dose. Approximately 11% of CT examinations performed are in the paediatric population, but the long‐term hazards of CT are unknown.
radiation; paediatrics; computed tomography; nuclear medicine; radiography
Extra‐hepatic biliary atresia occurs in approximately 1:15 000 live births leading to about 50 new cases/year in the UK. Presentation is with prolonged jaundice, usually in a term baby who develops signs of obstructive jaundice. Management has been improved by public and professional education to encourage early referral and diagnosis to facilitate initial surgery before 8 weeks of age. Surgical management is complementary and includes an attempt to restore biliary flow (the Kasai portoenterostomy) and liver transplantation if necessary. Medical management consists of antibiotics, ursodeoxycholic acid to encourage bile flow, fat soluble vitamin supplementation and nutritional support. Centralising surgery to specialised centres has improved survival of this potentially fatal disease to over 90% in the UK. Over half of infants undergoing portoenterostomy will clear the jaundice and have a greater than 80% chance of a good quality of life, reaching adolescence without transplantation. For those children developing intractable complications of cirrhosis and portal hypertension, liver transplantation provides a 90% chance of achieving normal life.
Diabetes; children; insulin analogues; HbA1c; CSII
The underlying pathogenesis of asthma, one of the most common chronic diseases of childhood, is not fully understood. There is a well‐documented heritable component to this disease and environmental factors associated with a Westernised lifestyle have also been implicated; recent studies suggest gene–environment interactions are important in the development of this disease. In the absence of a previous review in children, the present report presents the accumulating evidence for gene–environment interactions in asthma pathogenesis. Studies of these interactions in different populations have yielded both expected and unexpected results. This is a new and rapidly developing field where there are currently many more questions than answers.
You can't teach old dogs new tricks. Teaching middle‐aged dogs new tricks is hard enough. They tend to stick to particular styles of attacking the postman that over the years have proved pretty reliable, often choosing to ignore new findings, or simply failing to keep up with progress in current discussions on, say, the old trouser versus postbag debate. Some unsettling papers are even asking whether dogs really need to attack postmen at all.
The successful use of gene therapy to correct rare immune system disorders has highlighted the enormous potential of such therapies. We review the current state of gene therapy for childhood immune system disorders, and consider why these conditions have been particularly amenable to genetic correction. As with all emerging therapies, there have been unexpected side effects and their underlying mechanisms are the subject of intense research. Minimising such risks through improved vector design will play an important role in developing the next generation of gene based therapies and extending their applicability.
gene therapy; retroviral vectors; severe combined immunodeficiency
Serogroup C meningococcal conjugate vaccines, first launched in the UK in 1999, have been used successfully in Australia, Canada and several other European countries. Combination conjugate vaccines, containing more than one meningococcal polysaccharide, have been developed to broaden protection against the disease. A tetravalent meningococcal A, C, Y and W‐135 conjugate vaccine was licensed for use in 11–55 year old adolescents and adults in the US in January 2005, and subsequently also in 2–11 year old children in Canada in May 2006. This article discusses the different glycoconjugate meningococcal vaccines which have been developed and the potential for their use to control disease caused by serogroups A, C, Y and W‐135 of Neisseria meningitidis.
conjugate meningococcal vaccines; tetravalent meningococcal vaccines; meningococcal meningitis;
Neisseria meningitidis serogroups A, C, Y, W‐135; vaccine immunology
Our aim was to develop guidance for general paediatricians and primary care physicians in diagnosing and managing cow's milk protein allergy in infants. The guidelines were developed by discussion based on existing national recommendations and standards, clinical experience and, whenever possible, evidence from the literature. Separate algorithms cover breast‐fed and formula‐fed infants. The recommendations emphasise the importance of comprehensive history taking and careful physical examination. Patients with severe symptoms need to be referred to a specialist. Elimination of cow's milk protein from the infant's or mother's diet and challenges are the gold standard for diagnosis. This guidance is intended as a basis for local discussion, implementation and prospective evaluation. The algorithms should be regularly assessed using clinical audit standards. Once validated, the diagnostic framework could provide a standardised approach in epidemiological and therapeutic studies.
Cardiac arrest in children is not often due to a disturbance in rhythm that is amenable to electrical defibrillation, contrary to the situation in adults. When a shockable rhythm is present, defibrillation using an external electric shock applied at an early stage after pre‐oxygenation and chest compressions is of proven efficacy. Success at conversion of ventricular fibrillation is dependent on the delay before delivering the shock and defibrillation efficiency, which is itself a function of thoracic impedance, energy dose and waveform.
This article provides a framework for understanding how Muslim identity, and the current social and political contexts in which it is shaped, affects the health of Muslims in the UK and the US, and the quality of health care they receive. Key medical and public health literature that addresses health concerns related to Muslim communities in the UK and the US is reviewed. Few data exist specific to health disparities for Muslim minorities. However, the article focuses on emerging studies concerning the consequences of “Islamophobia” for the physical and mental health and health care of Muslim families and children. We argue that, despite substantive structural differences in the health care systems of the UK and the US, social structural and political forces play similar roles in the health of Muslim children in both countries. Finally, we call for significant cultural and institutional adjustments in health care settings and further research studies to provide specific data to address health disparities for these growing and diverse populations.