Richard Tomlinson

Towards a definition of neurodisability: a Delphi survey

The aim of this study was to develop, systematically, a consensus‐based definition for ‘neurodisability’ that is meaningful to health professionals and parents of children with neurological conditions.

H1N1 Antibody Persistence 1 Year After Immunization With an Adjuvanted or Whole-Virion Pandemic Vaccine and Immunogenicity and Reactogenicity of Subsequent Seasonal Influenza Vaccine: A Multicenter Follow-on Study

Two doses of AS03B-adjuvanted pandemic influenza vaccine may be sufficient to maintain seroprotection across 2 influenza seasons. Administration of trivalent influenza vaccine to children who previously received 2 doses of pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain.

Meaningful health outcomes for paediatric neurodisability: Stakeholder prioritisation and appropriateness of patient reported outcome measures

BackgroundHealth services are increasingly focused on measuring and monitoring outcomes, particularly those that reflect patients’ priorities. To be meaningful, outcomes measured should be valued by patients and carers, be consistent with what health professionals seek to achieve, and be robust in terms of measurement properties.The aim of this study was (i) to seek a shared vision between families and clinicians regarding key aspects of health as outcomes, beyond mortality and morbidity, for children with neurodisability, and (ii) to appraise which multidimensional patient reported outcome measures (PROMs) could be used to assess salient health domains.MethodsRelevant outcomes were identified from (i) qualitative research with children and young people with neurodisability and parent carers, (ii) Delphi survey with health professionals, and (iii) systematic review of PROMs. The International Classification of Functioning Disability and Health provided a common language to code aspects of health. A subset of stakeholders participated in a prioritisation meeting incorporating a Q-sorting task to discuss and rank aspects of health.ResultsA total of 33 pertinent aspects of health were identified. Fifteen stakeholders from the qualitative and Delphi studies participated in the prioritisation meeting: 3 young people, 5 parent carers, and 7 health professionals. Aspects of health that emerged as more important for families and targets for health professionals were: communication, emotional wellbeing, pain, sleep, mobility, self-care, independence, mental health, community and social life, behaviour, toileting and safety. Whilst available PROMs measure many aspects of health in the ICF, no single PROM captures all the key domains prioritised as for children and young people with neurodisability. The paucity of scales for assessing communication was notable.ConclusionsWe propose a core suite of key outcome domains for children with neurodisability that could be used in evaluative research, audit and as health service performance indicators. Future work could appraise domain-specific PROMs for these aspects of health; a single measure assessing the key aspects of health that could be applied across paediatric neurodisability remains to be developed.

The Healthy Lifestyles Programme (HeLP), a novel school-based intervention to prevent obesity in school children: study protocol for a randomised controlled trial

BackgroundOver the last three decades there has been a substantial increase in the proportion of children who are overweight or obese. The Healthy Lifestyles Programme (HeLP) is a novel school-based intervention, using highly interactive and creative delivery methods to prevent obesity in children.Methods/DesignWe describe a cluster randomised controlled trial to evaluate the effectiveness and cost effectiveness of HeLP. The intervention has been developed using intervention mapping (involving extensive stakeholder involvement) and has been guided by the Information, Motivation, Behavioural Skills model. HeLP includes creating a receptive environment, drama activities, goal setting and reinforcement activities and runs over three school terms. Piloting showed that 9 to 10 year olds were the most receptive and participative. This study aims to recruit 1,300 children from 32 schools (over half of which will have ≥19% of pupils eligible for free school meals) from the southwest of England. Participating schools will be randomised to intervention or control groups with baseline measures taken prior to randomisation. The primary outcome is change in body mass index standard deviation score (BMI SDS) at 24 months post baseline. Secondary outcomes include, waist circumference and percent body fat SDS and proportion of children classified as overweight or obese at 18 and 24 months and objectively measured physical activity and food intake at 18 months. Between-group comparisons will be made using random effects regression analysis taking into account the hierarchical nature of the study design. An economic evaluation will estimate the incremental cost-effectiveness of HeLP, compared to control, from the perspective of the National Health Service (NHS)/third party payer. An in-depth process evaluation will provide insight into how HeLP works, and whether there is any differential uptake or engagement with the programme.DiscussionThe results of the trial will provide evidence on the effectiveness and cost effectiveness of the Healthy Lifestyles Programme in affecting the weight status of children.Trial registrationISRCTN15811706

Once daily ceftriaxone and gentamicin for the treatment of febrile neutropenia

AIMS To evaluate the pharmacokinetics of once daily (OD) gentamicin and its effectiveness as part of an OD regimen for the empirical treatment of febrile neutropenia in children with cancer. SUBJECTS 59 children aged 6 months to 16 years (mean (SD) 5.7 (4) years) with febrile neutropenia (neutrophil count <u20090.5u2009×u2009109/l) after chemotherapy. METHODS Over one year, 113 febrile neutropenic episodes were treated empirically with an OD antibiotic regimen of ceftriaxone (80u2009mg/kg; maximum 4u2009g) and gentamicin (7u2009mg/kg; infused over 60 minutes, no maximum). The patients were assessed after 48 hours. RESULTS 86 of the 113 episodes settled with the first line antibiotic regimen. In 29 episodes, blood cultures identified a causative bacterial pathogen; for 17 of these, the first line antibiotic regimen was adequate; in four episodes, although the episode settled, ceftriaxone was replaced by a more appropriate antibiotic and OD gentamicin was continued; in the remaining eight episodes, a glycopeptide antibiotic was deemed necessary. There was no failure of treatment in organisms sensitive to gentamicin, including Pseudomonas aeruginosa. In 27 episodes (24%), resolution was obtained by the empirical introduction of a second line regimen of ceftazidime and a glycopeptide antibiotic, and/or amphotericin. Gentamicin concentrations were measured in 110 episodes and they were all below the 24 hour line indicating that there was no need to change the dosing interval. In two episodes (2%), serum creatinine rose transiently by more than 50% of the baseline concentration. Although there was no vestibular toxicity, three of 30 children who underwent pure tone audiometry reported high frequency hearing loss in one ear. CONCLUSION OD gentamicin can be used safely and effectively to treat febrile neutropenia in children with cancer. When used for a short period (<u20095 days), in children not receiving other nephrotoxic drugs and who have normal serum creatinine, serum gentamicin estimations are unnecessary.

Health outcomes for children with neurodisability: what do professionals regard as primary targets?

Aim To identify what aspects of health clinicians target when working with children with neurodisability, and which might be appropriate to assess the performance of health services. Method Health professionals were recruited through child development teams and professional societies in England. Professionals participated in four rounds of an online Delphi survey. Open questions were used to elicit aspects of health; these were coded using the WHO International Classification of Functioning, Disability and Health for Children and Youth. Then, participants were asked to rate their agreement with statements to prioritise outcomes identified. Results Responses to all four rounds were, respectively: 233/276 (84.4%), 232/286 (81.1%), 227/285 (79.6%) and 191/284 (67.3%). The key outcome domains identified were: mental health, confidence/emotional stability, anxiety/attention, sleep, pain, toileting, movement ability, manual ability, acquiring skills, communication, mobility, self-care, recreation and leisure. Participants rated both functioning and well-being in these aspects of health as equally important. Interpretation This Delphi survey identified nine key domains that provide a professional perspective on a core set of outcomes for evaluating services for children and young people with neurodisability.

Communicating with disabled children when inpatients: barriers and facilitators identified by parents and professionals in a qualitative study

Communication is a fundamental part of health care, but can be more difficult with disabled children. Disabled children are more frequently admitted to hospital than other children.

Prevention of vaccine-matched and mismatched influenza in children aged 6–35 months: a multinational randomised trial across five influenza seasons

BACKGROUNDnDespite the importance of vaccinating children younger than 5 years, few studies evaluating vaccine prevention of influenza have been reported in this age group. We evaluated efficacy of an inactivated quadrivalent influenza vaccine (IIV4) in children aged 6-35 months.nnnMETHODSnIn this phase 3, observer-blinded, multinational trial, healthy children from 13 countries in Europe, Central America, and Asia were recruited in five independent cohorts, each in a different influenza season. Participants were randomly assigned (1:1) to either IIV4 (15 μg haemagglutinin antigen per strain per 0·5 mL dose; a single dose on day 0 for vaccine-primed children, and two doses, on days 0 and 28, for vaccine-unprimed children) or to one or two doses of a non-influenza control vaccine. Primary endpoints were moderate-to-severe influenza or all influenza (irrespective of disease severity) confirmed by RT-PCR on nasal swabs. Cultured isolates were further characterised as antigenically matched or mismatched to vaccine strains. Efficacy was assessed in the per-protocol cohort and total vaccinated cohort (time-to-event analysis), and safety was assessed in the total vaccinated cohort.nnnFINDINGSnBetween Oct 1, 2011, and Dec 31, 2014, 12u2008018 children were recruited into the total vaccinated cohort (6006 children in the IIV4 group and 6012 children in the control group). 356 (6%) children in the IIV4 group and 693 (12%) children in the control group had at least one case of RT-PCR-confirmed influenza. Of these 1049 influenza strains, 138 (13%) were A/H1N1, 529 (50%) were A/H3N2, 69 (7%) were B/Victoria, and 316 (30%) were B/Yamagata. Overall, 539 (64%) of 848 antigenically characterised isolates were vaccine-mismatched (16 [15%] of 105 for A/H1N1; 368 [97%] of 378 for A/H3N2; 54 [86%] of 63 for B/Victoria; 101 [33%] of 302 for B/Yamagata). Vaccine efficacy was 63% (97·5% CI 52-72) against moderate-to-severe influenza and 50% (42-57) against all influenza in the per-protocol cohort, and 64% (53-73) against moderate-to-severe influenza and 50% (42-57) against all influenza in the total vaccinated cohort. There were no clinically meaningful safety differences between IIV4 and control.nnnINTERPRETATIONnIIV4 prevented influenza A and B in children aged 6-35 months despite high levels of vaccine mismatch. Vaccine efficacy was highest against moderate-to-severe disease, which is the most clinically important endpoint associated with greatest burden.nnnFUNDINGnGlaxoSmithKline Biologicals SA.

A 1-year follow-on study from a randomised, head-to-head, multicentre, open-label study of two pandemic influenza vaccines in children

INTRODUCTIONnPandemic influenza A H1N1 infections occurred worldwide from 2009. Children were particularly vulnerable. Novel vaccines were used during the pandemic.nnnOBJECTIVEnTo assess the persistence of antibody to H1N1 influenza 1 year after children aged 6 months to 12 years had been immunised with two doses of either a non-adjuvanted whole-virion H1N1 influenza vaccine or an AS03B-adjuvanted split-virion H1N1 influenza vaccine; and also to assess the immunogenicity and reactogenicity in this population of a single dose of 2010-11 trivalent seasonal influenza vaccine.nnnDESIGNnMulticentre, open-label, follow-on from randomised, head-to-head trial.nnnSETTINGnFive UK sites (Southampton, Oxford, Bristol, London and Exeter).nnnPARTICIPANTSnChildren who completed last years head-to-head randomised study were invited to participate. Children who had subsequently received a further dose of H1N1 vaccine, or who had already received a dose of 2010-11 trivalent seasonal influenza vaccine, were excluded.nnnINTERVENTIONSnIn the previous study, children were randomised (in a 1 : 1 ratio) to receive two doses, 21 days apart, of either a non-adjuvanted whole-virion H1N1 influenza vaccine or an AS03B-adjuvanted split-virion H1N1 influenza vaccine. In this follow-on study, a blood sample was taken to assess the persistence of antibody 1 year later, followed by administration of one 0.5 ml-dose of trivalent seasonal influenza vaccine. A second blood sample was taken 3 weeks later.nnnMAIN OUTCOME MEASURESnComparison between vaccines of the percentage of participants with a microneutralisation (MN) titre ≥ 1 : 40 and a haemagglutination titre ≥ 1 : 32, 1 year after vaccination. Immunogenicity of the trivalent seasonal influenza vaccine was assessed 3 weeks after vaccination by both the MN and the haemagglutination inhibition (HI) titres. Reactogenicity data were recorded for 7 days after vaccination.nnnRESULTSnA total of 323 children were enrolled and 318 were included in the analysis of the persistence of antibody. One year after receipt of whole-virion vaccine, the MN titre was ≥ 1 : 40 in 32.4% of those vaccinated when < 3 years old and in 65.9% of those vaccinated when ≥ 3 years old; the HI titre was ≥ 1 : 32 in 63.2% and 79.1% of children in the respective age groups. One year after receipt of the adjuvanted vaccine, the MN titre was ≥ 1 : 40 in 100% of those vaccinated when < 3 years old and in 96.9% of those vaccinated when ≥ 3 years old; the HI titre was ≥ 1 : 32 in 98.4% and 96.9% of children in the respective age groups. Three hundred and two children were given trivalent seasonal influenza vaccination. Three weeks later, sera were obtained from 282 children; 100% had an MN titre ≥ 1 : 40 and HI titre ≥ 1 : 32. Trivalent seasonal influenza vaccine was well tolerated, although in children < 5 years old, fever ≥ 38 °C was reported in 13.6% of those who had previously received whole-virion vaccine, and in 18.3% of those who had received adjuvanted vaccine.nnnCONCLUSIONSnNearly all children who received two doses of AS03B-adjuvanted split-virion pandemic H1N1 influenza vaccine had titres of antibody deemed protective (HI titre ≥ 1 : 32, MN titre ≥ 1 : 40) 1 year later. Children who received two doses of whole-virion vaccine had lower titres, although many were above the putative protective thresholds. One year after either pandemic vaccine, the 2010-11 trivalent seasonal influenza vaccine produced a marked serological response to the H1N1 component of the vaccine and was well tolerated. We propose to investigate whether or not previous receipt of monovalent influenza vaccines affected serological response to the H3N2 and B components of the 2010-11 seasonal influenza vaccine, using stored sera.nnnTRIAL REGISTRATIONnClinicalTrials.gov NCT01239537.nnnFUNDINGnThe National Institute for Health Research Health Technology Assessment programme.

Effectiveness of the Healthy Lifestyles Programme (HeLP) to prevent obesity in UK primary-school children: a cluster randomised controlled trial

Summary Background Although childhood overweight and obesity prevalence has increased substantially worldwide in the past three decades, scarce evidence exists for effective preventive strategies. We aimed to establish whether a school-based intervention for children aged 9–10 years would prevent excessive weight gain after 24 months. Methods This pragmatic cluster randomised controlled trial of the Healthy Lifestyles Programme (HeLP), a school-based obesity prevention intervention, was done in 32 schools in southwest England. All state-run primary and junior schools in Devon and Plymouth (UK) with enough pupils for at least one year-5 class were eligible. Schools were assigned (1:1) using a computer-generated sequence to either intervention or control, stratified by the number of year-5 classes (one vs more than one) and the proportion of children eligible for free school meals (<19% [the national average] vs ≥19%). HeLP was delivered to year-5 children (ages 9–10 years) over 1 year, and included dynamic and interactive activities such as physical activity workshops, education sessions delivered by teachers with short homework tasks, drama sessions, and setting goals to modify behaviour (with parental support and one-to-one discussions with HeLP coordinators). The primary outcome was change in body-mass index (BMI) standard deviation score (SDS) between baseline and 24 months, analysed in children with BMI data available for both timepoints. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN15811706, and the trial status is complete. Findings Between March 21, 2012, and Sept 30, 2013, 32 eligible schools with 1324 children were recruited, of which 16 schools (676 children) were randomly assigned to the HeLP intervention and 16 schools (648 children) to control. All schools that began the trial completed the intervention, and 1244 children (628 in intervention group and 616 in control group) had BMI data at both baseline and 24 months for the primary outcome analysis. Mean BMI SDS was 0·32 (SD 1·16) at baseline and 0·35 (1·25) at 24 months in the intervention group, and 0·18 (1·14) at baseline and 0·22 (1·22) at 24 months in the control group. With adjustment for school-level clustering, baseline BMI scores, sex, cohort, and number of year-5 classes and socioeconomic status of each school, the mean difference in BMI SDS score (intervention–control) at 24 months was −0·02 (95% CI −0·09 to 0·05), p=0·57. One parent reported an adverse event related to their childs eating and activity behaviours, but agreed for the child to continue trial participation after discussion with the chief investigator. Interpretation Despite a theoretically informed and extensively piloted intervention that achieved high levels of engagement, follow-up, and fidelity of delivery, we found no effect of the intervention on preventing overweight or obesity. Although schools are an ideal setting in which to deliver population-based interventions, school-based interventions might not be sufficiently intense to affect both the school and the family environment, and hence the weight status of children. Future research should focus on more upstream determinants of obesity and use whole-systems approaches. Funding UK National Institute for Health Research, Public Health Research Programme.