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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.  Ethnic and sex differences in skeletal maturation among the Birth to Twenty cohort in South Africa 
Archives of Disease in Childhood  2014;100(2):138-143.
To examine ethnic and sex differences in the pattern of skeletal maturity from adolescence to adulthood using a novel longitudinal analysis technique (SuperImposition by Translation And Rotation (SITAR)).
Johannesburg, South Africa.
607 boys and girls of black as well as white ethnicity from the Birth to Twenty bone health study, assessed annually from 9 to 20 years of age.
Outcome measure
Bone maturity scores (Tanner–Whitehouse III radius, ulna, and short bones (TW3 RUS)) assessed longitudinally from hand-wrist radiographs were used to produce individual and mean growth curves of bone maturity and analysed by the SITAR method.
The longitudinal analysis showed that black boys matured later by 7.0 SE 1.6 months (p<0.0001) but at the same rate as white boys, whereas black girls matured at the same age but at a faster rate than white girls (by 8.7% SE 2.6%, p=0.0007). The mean curves for bone maturity score consistently showed a midpubertal double kink, contrasting with the quadratic shape of the commonly used reference centile curves for bone maturity (TW3).
Skeletal maturity was reached 1.9 years earlier in girls than boys, and the pattern of maturation differed between the sexes. Within girls, there were no ethnic differences in the pattern or timing of skeletal maturity. Within boys, however, skeletal maturity was delayed by 7 months in black compared with white ethnicity. Skeletal maturation, therefore, varies differentially by sex and ethnicity. The delayed maturity of black boys, but not black girls, supports the hypothesis that boys have greater sensitivity to environmental constraints than girls.
PMCID: PMC4316919  PMID: 25409981
Adolescent Health; Growth
3.  Knowledge and skills retention following Emergency Triage, Assessment and Treatment plus Admission course for final year medical students in Rwanda: a longitudinal cohort study 
Archives of Disease in Childhood  2014;99(11):993-997.
To determine whether, after the Emergency Triage, Assessment and Treatment plus Admission (ETAT+) course, a comprehensive paediatric life support course, final year medical undergraduates in Rwanda would achieve a high level of knowledge and practical skills and if these were retained. To guide further course development, student feedback was obtained.
Longitudinal cohort study of knowledge and skills of all final year medical undergraduates at the University of Rwanda in academic year 2011–2012 who attended a 5-day ETAT+ course. Students completed a precourse knowledge test. Knowledge and clinical skills assessments, using standardised marking, were performed immediately postcourse and 3–9 months later. Feedback was obtained using printed questionnaires.
84 students attended the course and re-evaluation. Knowledge test showed a significant improvement, from median 47% to 71% correct answers (p<0.001). For two clinical skills scenarios, 98% passed both scenarios, 37% after a retake, 2% failed both scenarios. Three to nine months later, students were re-evaluated, median score for knowledge test 67%, not significantly different from postcourse (p>0.1). For clinical skills, 74% passed, with 32% requiring a retake, 8% failed after retake, 18% failed both scenarios, a significant deterioration (p<0.0001).
Students performed well on knowledge and skills immediately after a comprehensive ETAT+ course. Knowledge was maintained 3–9 months later. Clinical skills, which require detailed sequential steps, declined, but most were able to perform them satisfactorily after feedback. The course was highly valued, but several short courses and more practical teaching were advocated.
PMCID: PMC4198299  PMID: 24925893
Medical Education; Accident & Emergency; Resuscitation; Low income populations; Rwanda
4.  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
5.  Back to school: challenges and rewards of engaging young children in scientific research 
Archives of Disease in Childhood  2016;101(9):785-787.
PMCID: PMC5013085  PMID: 27117837
children; Health services research; recruitment
6.  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
7.  Why do young children die in the UK? A comparison with Sweden 
Archives of Disease in Childhood  2015;100(10):928-931.
The UK has a high child mortality rate, whereas Sweden's is lower (under-five mortality rates of five and three, respectively, in 2011).We therefore wished to compare causes of death in young children aged <5 years in the two countries.
Under-five mortality data were obtained from the Office of National Statistics for each of the individual countries within the UK for 3 years (2006–2008). Data for Sweden for the same period were obtained from the National Board of Health and Welfare. Causes of death were compared statistically using χ2 test.
There were a total of 14 104 and 1036 deaths aged <5 years in the UK and Sweden, respectively, between 2006 and 2008. The total numbers of live births during the same period were 2 295 964 and 315 884, respectively. The overall mortality rate in the UK was 614 per 100 000 children which was significantly higher than that in Sweden (328; p<0.001). The mortality rates for the three main causes of death in the UK (prematurity, congenital malformations and infections) were 138.5, 112.1 and 63.9, respectively, per 100 000 children. The mortality rates for the same three conditions in Sweden were 10.1, 88.6 and 34.8, respectively. They were all significantly more frequent in the UK than in Sweden (p<0.001), as were the majority of the disorders. Treatable infections, such as pneumonia, meningitis and septicaemia, in both neonates and young children had significantly higher mortality rates in the UK than in Sweden (p<0.001).
In order to reduce the mortality rate in the UK, we need to try and reduce the causes of prematurity. Additionally, the care of children with treatable infections should be reviewed to understand ways in which to reduce the differences in mortality seen.
PMCID: PMC4602244  PMID: 26272911
Health services research; Pharmacology; Outcomes research; Comm Child Health
8.  Blood pressure centiles for Great Britain 
Archives of Disease in Childhood  2006;92(4):298-303.
To produce representative cross‐sectional blood pressure reference centiles for children and young people living in Great Britain.
Analysis of blood pressure data from seven nationally representative surveys: Health Surveys for England 1995–8, Scottish Health Surveys 1995 and 1998, and National Diet & Nutrition Survey 1997.
Blood pressure was measured using the Dinamap 8100 with the same protocol throughout. Weight and height were also measured. Data for 11 364 males and 11 537 females aged 4–23 years were included in the analysis, after excluding 0.3% missing or outlying data. Centiles were derived for systolic, diastolic, mean arterial and pulse pressure using the latent moderated structural (LMS) equations method.
Blood pressure in the two sexes was similar in childhood, rising progressively with age and more rapidly during puberty. Systolic pressure rose faster and was appreciably higher in adult men than in adult women. After adjustment for age, blood pressure was related more to weight than height, the effect being stronger for systolic blood pressure. Pulse pressure peaked at 18 years in males and 16 years in females.
These centiles increase our knowledge of blood pressure norms in contemporary British children and young people. High blood pressure for age should be defined as blood pressure above the 98th centile, and high‐normal blood pressure for age as blood pressure between the 91st and 98th centiles. The centiles identify children and young people with increased blood pressure, and will be of benefit to both clinical practice and research.
PMCID: PMC2083671  PMID: 16905566
9.  Withdrawal of ventilatory support outside the intensive care unit: guidance for practice 
Archives of Disease in Childhood  2014;99(9):812-816.
To review the work of one tertiary paediatric palliative care service in facilitating planned withdrawal of ventilatory support outside the intensive care setting, with the purpose of developing local guidance for practice.
Retrospective 10-year (2003–2012) case note review of intensive care patients whose parents elected to withdraw ventilation in another setting. Demographic and clinical data revealed common themes and specific incidents relevant to local guideline development.
18 children (aged 2 weeks to 16 years) were considered. Three died prior to transfer. Transfer locations included home (5), hospice (8) and other (2). Primary pathologies included malignant, neurological, renal and respiratory diseases. Collaborative working was evidenced in the review including multidisciplinary team meetings with the palliative care team prior to discharge. Planning included development of symptom management plans and emergency care plans in the event of longer than anticipated survival. Transfer of children and management of extubations demonstrated the benefits of planning and recognition that unexpected events occur despite detailed planning. We identified the need for local written guidance supporting healthcare professionals planning and undertaking extubation outside the intensive care setting, addressing the following phases: (i) introduction of withdrawal, (ii) preparation pretransfer, (iii) extubation, (iv) care postextubation and (v) care postdeath.
Planned withdrawal of ventilatory support outside the intensive care setting is challenging and resource intensive. The development of local collaborations and guidance can enable parents of children dependent on intensive care to consider a preferred place of death for their child, which may be outside the intensive care unit.
PMCID: PMC4145452  PMID: 24951460
Palliative Care; Guildlines; Paediatric Intensive Care (PICU); Place of Death
10.  A qualitative study of uptake of free vitamins in England 
Archives of Disease in Childhood  2013;98(8):587-591.
To identify reasons why eligible families are not accessing free ‘Healthy Start’ vitamin supplementation (providing vitamins A, C and D) in England.
Qualitative study using in-depth interviews.
13 primary care trusts in England.
Purposive sample of 15 Healthy Start coordinators, 50 frontline health and children's professionals and 107 parents.
Vitamin take-up was low across all research sites, reported as below 10% of eligible beneficiaries for free vitamins. Reasons identified by both parents and professionals included (1) poor accessibility of vitamins, (2) low promotion of the scheme by health professionals, (3) a lack of awareness among eligible families, and (4) low motivation among mothers to take vitamins for themselves during pregnancy or for children under 4 years old.
Low uptake rates can be explained by poor accessibility of vitamins and lack of awareness and motivation to take vitamin supplements among eligible families. Universal provision (at least for pregnant women) and better training for health professionals are identified as potential solutions worthy of further research and evaluation.
PMCID: PMC3717763  PMID: 23702436
Epidemiology; General Paediatrics; Nursing; Health services research; Qualitative research
11.  Conflict in a paediatric hospital: a prospective mixed-method study 
Archives of Disease in Childhood  2015;101(1):23-27.
Conflict in healthcare is a well-recognised but under-examined phenomenon. Little is known about the prevalence and causes of conflict across paediatric specialties.
To report the frequency and characteristics of conflict in a paediatric hospital.
Design and setting
An explanatory sequential mixed-method approach was adopted. A bespoke questionnaire recorded frequency, severity, cause and staff involved in conflict prospectively. Data were recorded for the same two 12-week periods in 2013 and 2014, in one UK children's teaching hospital. Data were analysed using descriptive statistics and correlation, the findings of which informed the construction of a semistructured interview schedule. Qualitative interviews were conducted with six key informant healthcare professionals to aid data interpretation; interviews were analysed thematically.
136 individual episodes of conflict were reported. The three most common causes were ‘communication breakdown’, ‘disagreements about treatment’ and ‘unrealistic expectations’. Over 448 h of healthcare professional time was taken up by these conflicts; most often staff nurses, consultants, doctors in training and matrons. The mean severity rating was 4.9 out of 10. Qualitative interviews revealed consensus regarding whether conflicts were ranked as low, medium or high severity, and explanations regarding why neurology recorded the highest number of conflicts in the observed period.
Conflict is prevalent across paediatric specialties, and particularly in neurology, general paediatrics and neonatology. Considerable staff time is taken in managing conflict, indicating a need to focus resources on supporting staff to resolve conflict, notably managing communication breakdown.
PMCID: PMC4770249  PMID: 26553912
Paediatric Practice; Health services research
12.  Conflict escalation in paediatric services: findings from a qualitative study 
Archives of Disease in Childhood  2015;100(8):769-773.
To explore clinician and family experiences of conflict in paediatric services, in order to map the trajectory of conflict escalation.
Qualitative interview study, employing extreme-case sampling. Interviews were analysed using an iterative thematic approach to identify common themes regarding the experience and escalation of conflict.
Thirty-eight health professionals and eight parents. All participants had direct experience of conflict, including physical assault and court proceedings, at the interface of acute and palliative care.
Two teaching hospitals, one district general hospital and two paediatric hospices in England, in 2011.
Conflicts escalate in a predictable manner. Clearly identifiable behaviours by both clinicians and parents are defined as mild, moderate and severe. Mild describes features like the insensitive use of language and a history of unresolved conflict. Moderate involves a deterioration of trust, and a breakdown of communication and relationships. Severe marks disintegration of working relationships, characterised by behavioural changes including aggression, and a shift in focus from the child's best interests to the conflict itself. Though conflicts may remain at one level, those which escalated tended to move sequentially from one level to the next.
Understanding how conflicts escalate provides clinicians with a practical, evidence-based framework to identify the warning signs of conflict in paediatrics.
PMCID: PMC4518764  PMID: 25940425
General Paediatrics; Qualitative research; Ethics
13.  Research consent from young people in resource-poor settings 
Archives of Disease in Childhood  2014;100(5):438-440.
Authoritative international guidelines stipulate that for minors to participate in research, consent must be obtained from their parents or guardians. Significant numbers of mature minors, particularly in low-income settings, are currently being ruled out of research participation because their parents are unavailable or refuse to provide consent despite the possibility that they might wish to do so and that such research has the potential to be of real benefit. These populations are under-represented in all types of clinical research. We propose that, for research with a prospect of direct benefit that has been approved by relevant ethics committees, the default position should be that minors who are able to provide valid consent and meet the following criteria should be able to consent for themselves regardless of age and whether they have reached majority: the minor must be competent and mature relative to the decision; their consent must be voluntary and they must be relatively independent and used to decision making of comparable complexity. In addition, the context must be appropriate, the information related to the research must be provided in a manner accessible to the minor and the consent must be obtained by a trained consent taker in surroundings conducive for decision making by the minor. In this paper, we have argued that consent by mature minors to research participation is acceptable in some situations and should be allowed.
PMCID: PMC4413844  PMID: 25477309
Ethics; Adolescent Health; Tropical Paediatrics
14.  How safe is paracetamol? 
Archives of Disease in Childhood  2015;100(1):73-74.
PMCID: PMC4283624  PMID: 25512959
Pharmacology; Pain; General Paediatrics
15.  Blood pressure centiles for Great Britain 
Archives of Disease in Childhood  2006;92(4):298-303.
To produce representative cross-sectional blood pressure reference centiles for children and young people living in Great Britain.
Analysis of blood pressure data from seven nationally representative surveys: Health Surveys for England 1995–8, Scottish Health Surveys 1995 and 1998, and National Diet & Nutrition Survey 1997.
Blood pressure was measured using the Dinamap 8100 with the same protocol throughout. Weight and height were also measured. Data for 11 364 males and 11 537 females aged 4–23 years were included in the analysis, after excluding 0.3% missing or outlying data. Centiles were derived for systolic, diastolic, mean arterial and pulse pressure using the lambda-mu-sigma (LMS) equations method.
Blood pressure in the two sexes was similar in childhood, rising progressively with age and more rapidly during puberty. Systolic pressure rose faster and was appreciably higher in adult men than in adult women. After adjustment for age, blood pressure was related more to weight than height, the effect being stronger for systolic blood pressure. Pulse pressure peaked at 18 years in males and 16 years in females.
These centiles increase our knowledge of blood pressure norms in contemporary British children and young people. High blood pressure for age should be defined as blood pressure above the 98th centile, and high-normal blood pressure for age as blood pressure between the 91st and 98th centiles. The centiles identify children and young people with increased blood pressure, and will be of benefit to both clinical practice and research.
PMCID: PMC2083671  PMID: 16905566
16.  Adolescent inpatient activity 1999–2010: analysis of English Hospital Episode Statistics data 
Archives of Disease in Childhood  2014;99(9):830-833.
To investigate patterns and trends of adolescent (10–19 years) inpatient activity in England by sex, disease category, and admitting speciality.
9 632 844 Finished Consultant Episodes (FCEs) from English patients aged 1–19 between 1999/2000 and 2010/2011 (Hospital Episode Statistics data).
Age trends by sex and major International Classification of Disease 10 (ICD10) chapter; differences in activity rates by age and sex; inpatient activity trends over the past decade, disaggregated by sex, admitting speciality and ICD10 chapter.
Adolescent female patients account for more activity than girls aged 1–9 (139.4 vs 107.2 FCEs/1000). Female inpatient activity increases significantly between age 10 (70.9 FCEs/1000) and 19 (281.7 FCES/1000, of which non-obstetric care accounts for 155.9 FCEs/1000). Male activity increases much less during adolescence, with lower overall rates among adolescents than younger children (93.7 vs 142.9 FCEs/1000). Between 1999 and 2010, total adolescent inpatient activity increased faster among adolescents (10–19 years) (+14.2%) than younger children (1–9 years) (+11.0%). Adolescent FCEs/1000 increased by 12.8%, including higher rates admitted under Paediatrics (+47.5%) and Paediatric Surgery (+23.2%). Adolescents were admitted across a range of specialities.
These data challenge the belief that adolescents are a healthy group who rarely use inpatient services. In England, use of inpatient services is higher among female patients aged 10–19 years than those aged 1–9 years, while adolescent activity has increased faster than for younger children over the past 11 years. Improving service quality for adolescents will require engagement of the many different teams that care for them.
PMCID: PMC4145459  PMID: 24790134
Adolescent Health; Health services research
17.  Evaluation of temperature–pulse centile charts in identifying serious bacterial illness: observational cohort study 
Archives of Disease in Childhood  2011;96(4):368-373.
Distinguishing serious bacterial infection (SBI) from milder/self-limiting infections is often difficult. Interpretation of vital signs is confounded by the effect of temperature on pulse and respiratory rate. Temperature–pulse centile charts have been proposed to improve the predictive value of pulse rate in the clinical assessment of children with suspected SBI.
To assess the utility of proposed temperature–pulse centile charts in the clinical assessment of children with suspected SBI.
Study design and participants
The predictive value for SBI of temperature–pulse centile categories, pulse centile categories and Advanced Paediatric Life Support (APLS) defined tachycardia were compared among 1360 children aged 3 months to 10 years presenting with suspected infection to a hospital emergency department (ED) in England; and among 325 children who presented to hospitals in the UK with meningococcal disease.
Main outcome measure
Among children presenting to the ED, 55 (4.0%) had SBI. Pulse centile category, but not temperature–pulse centile category, was strongly associated with risk of SBI (p=0.0005 and 0.288, respectively). APLS defined tachycardia was also strongly associated with SBI (OR 2.90 (95% CI 1.60 to 5.26), p=0.0002). Among children with meningococcal disease, higher pulse and temperature–pulse centile categories were both associated with more severe disease (p=0.004 and 0.041, respectively).
Increased pulse rate is an important predictor of SBI, supporting National Institute for Health and Clinical Excellence recommendations that pulse rate be routinely measured in the assessment of febrile children. Temperature–pulse centile charts performed more poorly than pulse alone in this study. Further studies are required to evaluate their utility in monitoring the clinical progress of sick children over time.
PMCID: PMC3158667  PMID: 21233079
18.  Fit to WHO weight standard of European infants over time 
Archives of Disease in Childhood  2016;101(5):455-460.
The 2006 WHO growth charts were created to provide an international standard for optimal growth, based on healthy, breastfed populations, but it has been suggested that Northern European children fit them poorly. This study uses infant weight data spanning 50 years to determine how well-nourished preschool children from different eras fit the WHO standard, and discuss the implications of deviations.
Four longitudinal datasets from the UK and one from Finland were used comprising over 8000 children born between1959 and 2003. Weights from birth to 2 years were converted to age–sex-adjusted Z scores using the WHO standard and summarised using Generalized Additive Models for Location, Scale and Shape.
Weights showed a variable fit to the WHO standard. Mean weights for all cohorts were above the WHO median at birth, but dipped by up to 0.5 SD to a nadir at 8 weeks before rising again. Birth weights increased in successive cohorts and the initial dip became slightly shallower. By age 1 year, cohorts were up to 0.75 SD above the WHO median, but there was no consistent pattern by era.
The WHO standard shows an acceptable, but variable fit for Northern European infants. While birth weights increased over time, there was, unexpectedly, no consistent variation by cohort beyond this initial period. Discrepancies in weight from the standard may reflect differences in measurement protocol and trends in infant feeding practice.
PMCID: PMC4853582  PMID: 26883079
Epidemiology; General Paediatrics; Growth; Obesity; Nutrition
19.  Congenital laryngomalacia is related to exercise-induced laryngeal obstruction in adolescence 
Archives of Disease in Childhood  2016;101(5):443-448.
Congenital laryngomalacia (CLM) is the major cause of stridor in infants. Most cases are expected to resolve before 2 years of age, but long-term respiratory prospects are poorly described. We aimed to investigate if CLM was associated with altered laryngeal structure or function in later life.
Twenty of 23 (87%) infants hospitalised at Haukeland University Hospital during 1990–2000 for CLM without comorbidities and matched controls were assessed at mean age 13 years. Past and current respiratory morbidity was recorded in a questionnaire, and spirometry performed according to standard quality criteria. Laryngoscopy was performed at rest and continuously throughout a maximal treadmill exercise test (continuous laryngoscopy exercise test (CLE-test)), and scored and classified in a blinded fashion according to preset criteria.
In the CLM group, laryngeal anatomy supporting CLM in infancy was described at rest in nine (45%) adolescents. Eleven (55%) reported breathing difficulties in relation to exercise, of whom 7 had similarities to CLM at rest and 10 had supraglottic obstruction during CLE-test. Overall, 6/20 had symptoms during exercise and similarities to CLM at rest and obstruction during CLE-test. In the control group, one adolescent reported breathing difficulty during exercise and two had laryngeal obstruction during CLE-test. The two groups differed significantly from each other regarding laryngoscopy scores, obtained at rest and during exercise (p=0.001 or less).
CLM had left footprints that increased the risk of later exercise-induced symptoms and laryngeal obstruction. The findings underline the heterogeneity of childhood respiratory disease and the importance of considering early life factors.
PMCID: PMC4853585  PMID: 26906070
Exercise induced inspiratory symptoms; Congenital laryngomalacia; Vocal cord dysfunction; Respiratory Disorders; Follow-up study
20.  Health system strategies supporting transition to adult care 
Archives of Disease in Childhood  2015;100(6):559-564.
The transition from paediatric to adult care is associated with poor clinical outcomes, increased costs and low patient and family satisfaction. However, little is known about health system strategies to streamline and safeguard care for youth transitioning to adult services. Moreover, the needs of children and youth are often excluded from broader health system reform discussions, leaving this population especially vulnerable to system ‘disintegration’.
(1) To explore the international policy profile of paediatric-to-adult care transitions, and (2) to document policy objectives, initiatives and outcomes for jurisdictions publicly committed to addressing transition issues.
An international policy scoping review of all publicly available government documents detailing transition-related strategies was completed using a web-based search. Our analysis included a comparable cohort of nine wealthy Organisation for Economic Co-operation and Development (OECD) jurisdictions with Beveridge-style healthcare systems (deemed those most likely to benefit from system-level transition strategies).
Few jurisdictions address transition of care issues in either health or broader social policy documents. While many jurisdictions refer to standardised practice guidelines, a few report the intention to use powerful policy levers (including physician remuneration and non-physician investments) to facilitate the uptake of best practice. Most jurisdictions do not address the policy infrastructure required to support successful transitions, and rigorous evaluations of transition strategies are rare.
Despite the well-documented risks and costs associated with a poor transition from paediatric to adult care, little policy attention has been paid to this issue. We recommend that healthcare providers engage health system planners in the design and evaluation of system-level, policy-sensitive transition strategies.
PMCID: PMC4453494  PMID: 25688098
Adolescent Health; General Paediatrics; Health services research; Paediatric Practice
21.  Inter-individual variation in midazolam clearance in children 
Archives of Disease in Childhood  2014;100(1):95-100.
To determine the extent of inter-individual variation in clearance of midazolam in children and establish which factors are responsible for this variation.
A systematic literature review was performed to identify papers describing the clearance of midazolam in children. The following databases were searched: Medline, Embase, International Pharmaceutical Abstracts, CINAHL and Cochrane Library. From the papers, the range in plasma clearance and the coefficient of variation (CV) in plasma clearance were determined.
25 articles were identified. Only 13 studies gave the full range of clearance values for individual patients. The CV was greater in critically ill patients (18%–170%) than non-critically ill patients (13%–54%). Inter-individual variation was a major problem in all age groups of critically ill patients. The CV was 72%–106% in preterm neonates, 18%–73% in term neonates, 31%–130% in infants, 21%–170% in children and 47%–150% in adolescents. The mean clearance was higher in children (1.1–16.7 mL/min/kg) than in neonates (0.78–2.5 mL/min/kg).
Large inter-individual variation was seen in midazolam clearance values in critically ill neonates, infants, children and adolescents.
PMCID: PMC4283666  PMID: 25281734
Pharmacology; General Paediatrics
22.  Safety of new medicines in young children 
Archives of Disease in Childhood  2011;96(9):872-873.
PMCID: PMC3198508  PMID: 21836178
23.  Implications of adopting the WHO 2006 Child Growth Standard in the UK: two prospective cohort studies 
Archives of Disease in Childhood  2007;93(7):566-569.
The WHO 2006 Child Growth Standard is based on data from international optimally nourished breastfed infants from birth to age 5 years.
To assess the potential effect of its use on weight and growth monitoring of UK children.
Full-term members of two population-based UK birth cohorts: the Children in Focus sub-cohort of the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 1335) and the Gateshead Millennium Baby Study (GMS; n = 923).
Growth data from birth to 5 years were converted into z-scores relative to the WHO 2006 standard.
Compared with the WHO standard, both UK cohorts had higher birth weights (mean z-scores: GMS, 0.17; ALSPAC, 0.34) and ALSPAC had higher birth lengths. After birth, length showed a good fit at all ages. By 2–4 months, both cohorts were similar in weight to the WHO median (mean WHO weight z-score at 4 months: GMS, 0.01; ALSPAC, −0.07), but thereafter the UK cohorts were heavier (mean WHO weight z-score at 12 months: GMS, 0.57; ALSPAC, 0.65). At age 12 months, the risk of being classified as underweight (weight <2nd centile) was considerably lower according to the WHO standard than by the UK 1990 Growth Reference (RR = 0.15, 95% CI = 0.07 to 0.32), and the risk of being classified as obese at 4–5 years (body mass index >98th centile) was slightly increased (RR = 1.35, 95% CI = 1.02 to 1.78).
Adoption of the WHO 2006 Growth Charts would set a markedly lower standard of weight gain beyond the age of 4 months for UK infants and could support efforts to avoid future childhood obesity. However, the WHO standard is not representative of size at birth in the UK.
PMCID: PMC2532956  PMID: 17908712
24.  Why children do not receive treatment 
Archives of Disease in Childhood  2014;99(7):605-606.
PMCID: PMC4078697  PMID: 24748640
Children's Rights; General Paediatrics; Pharmacology
25.  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

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