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Background Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review. Objectives The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); 2. do not have unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. In addition, pharmaceutical companies were approached. Date of the most recent search of the Group's Trials Register: 29 September 2016. Selection criteria Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Data collection and analysis Four trials were identified by the searches; none of which was judged eligible for inclusion in the review. Main results No completed randomised controlled trials were included. Authors' conclusions At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although trials in people who do not have cystic fibrosis have shown clinical and serological evidence of improvement and a reduction in the use of corticosteroids with no increase in adverse effects. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Narcolepsy is a chronic disabling neurological sleep disorder that requires lifelong treatment. We have outlined the clinical features of narcolepsy, the assessment and diagnosis process and have summarised the existing treatment options for children and adolescents with narcolepsy. In the future, the approach to management of paediatric narcolepsy should ideally be in a multidisciplinary setting, involving specialists in sleep medicine, sleep physiology, neurologists and psychologists/psychiatrists. A multidisciplinary approach will help to manage the potential impact of narcolepsy on children and adolescents who are in a stage of their life that is critical to their physical, emotional and social development and their academic attainment.

The objective was to investigate the prevalence of Pseudomonas aeruginosa (PA) in patients with complex neurodisability and current treatment practice in our centre in order to inform future guidelines. A retrospective case note review was undertaken at a tertiary children’s hospital. One hundred sixty-two patients (mean age 11.7 years) with a primary diagnosis of neuromuscular disease (NMD) or severe cerebral palsy (CP) and a respiratory sample sent for analysis during the study period were studied. Associations between PA in respiratory samples and diagnosis, long-term ventilation, presence of a gastrostomy or a tracheostomy, antibiotic choice, clinical deterioration and adverse events were analysed. Twenty-five (15%) had one or more PA isolate in respiratory samples. There was a significant association between PA in respiratory samples and tracheostomy (pConclusions: A larger prospective study may establish clearer criteria for guideline development. Techniques such as point-of-care testing to identify virulent strains of PA may improve patient outcomes and prevent the development of antibiotic resistance in the future. What is Known:•Children with complex neurodisability are at increased risk of respiratory morbidity and of infection with gram-negative organisms such as Pseudomonas aeruginosa.•There are currently no guidelines to inform treatment choices in this group of vulnerable children. What is New:•15% children in this study population had Pseudomonas aeruginosa in respiratory samples during a 12-month period, the majority of whom did not require critical care treatment. Thirteen of these children had a tracheostomy in situ and 12 did not. •In those that deteriorated clinically or developed antibiotic resistant organisms, earlier detection and targeted treatment of Pseudomonas aeruginosa may have prevented deterioration.

The anatomical, physiological, and developmental changes which arise as children mature through childhood and adolescence support the need to develop new health technologies that meet the specific requirements of children and young people (CYP). Failing to involve CYP during the development of technology increases the risk that the outcome falls short of their expectations and needs, leading to rejection of novel interventions. Through participation in health technology development, CYP and their families can provide context, insight, personal experience and tacit knowledge to ensure that the end-product is usable, acceptable, and can be integrated into its intended environment. A nuanced, balanced understanding of the methods that can be used to facilitate participation will support researchers in choosing an effective approach to involving CYP in health technology development. Methodological approaches include patient and public involvement and engagement, co-design, and experienced based co-design. These methods can be used in isolation or in combination, to facilitate meaningful involvement of CYP and encourage the development of impactful solutions, in consideration of the context, stakeholders, and objectives of the project. We provide the rationale and justification for involving CYP in health technology design and development, an explanation of the methods supporting meaningful involvement, and case studies exemplifying real world application of these methods with positive outputs.

Non-invasive ventilation (NIV) is assisted mechanical ventilation delivered via a facemask for people with chronic conditions that affect breathing. NIV is most commonly delivered via an interface (mask) covering the nose (nasal mask) or the nose and mouth (oronasal mask). The number of children in the UK requiring NIV is currently estimated to be around 5000. Mass-produced masks are available for both the adult and paediatric markets but masks that fit well are difficult to find for children who are small or have asymmetrical facial features. A good conforming fit between the mask and the patient's face to minimise unintentional air leakage is essential to deliver the treatment effectively; most ventilators will trigger an alarm requiring action if such leakage is detected. We present an innovative use of 3D scanning and manufacturing technologies to deliver novel mask-face interfaces to optimise mask fit to the needs of individual patients. Ahead of planned user trials with paediatric patients, the project team trialled the feasibility of the process of creating and printing bespoke masks from 3D scan data and carried out testing of the masks in adult volunteers to select the strongest design concept for the paediatric trial. The evaluation of the process of designing a bespoke mask from scan data, arranging for its manufacture and carrying out user testing has been invaluable in gaining knowledge and discovering the pitfalls and timing bottlenecks in the processes. This allowed the team to iteratively refine the techniques and methods involved, informing user trials later on in the project. It has also provided indicative cost estimates for 3D printed mask prototype components which are useful in project decision making and trial planning. The value of the process extends to considerations for future implementation of the process within a clinical pathway.

Objective To assess the value of respiratory rate (RR) as a predictor of clinical deterioration in children, compared with other vital sign measurements. Design A retrospective case-control study, comparing children who deteriorated, requiring admission to critical care with children who did not deteriorate. Methods RR, heart rate (HR), and blood pressure (BP) measurements were collected from each patient for a 48-hour duration. The 95th centile was identified for each and 5% to 30% thresholds above the 95th centile were calculated. For each threshold the sensitivity, specificity, odds ratio, positive, and negative predictive value for deterioration was calculated. Results Forty cases (age range 7 weeks-15 years) and 40 control patients matched for age, gender, and hospital location were recruited. In 30/40 patients who deteriorated at least one RR ≥ 30% above the 95th centile for their age was recorded in the 48 hours before deterioration, compared with 10/40 controls, regardless of clinical diagnosis. Only 3/40 children that deteriorated had a HR > 30% greater than the 95th centile, compared with 2/40 controls. An elevated RR was the only vital sign whose odds ratios were significant at each threshold level above the 95th centile. Maximum RR occurred 16.8 hours before deterioration. Conclusion RR is a more accurate predictor of clinical deterioration in children than other vital signs. Greater weighting and importance should be placed on RR, which is often omitted in children due to difficulties with its measurement.

Non-invasive ventilation (NIV) is assisted mechanical ventilation delivered via a facemask for people with chronic conditions that affect breathing. Mass-produced masks are available for both the adult and paediatric markets but masks that fit well are difficult to find for children who are small or have asymmetrical facial features. A good fit between the mask and the patient's face to minimise unintentional air leakage is essential to deliver the treatment effectively. We present an innovative use of 3D assessment and manufacturing technologies to deliver novel custom-made facemasks for children for whom a well-fitting standard mask is not available. This paper aims to describe the processes undertaken to investigate and compare currently available technologies for 3D scanning children and to explore the design of a system for creating custom-made paediatric NIV masks within the NHS. The paper therefore considers not only the quality and accuracy of the data, but also other factors such as the time and ease of process. Searches for all currently available scanning technologies were made. Photogrammetry image stitch using a smartphone and a digital camera, and two structured light scanners were selected and compared in the laboratory, in discussion with user groups, and in adult volunteers. Using the processes described, it became apparent that the optimal 3D scanning system for this purpose was the handheld structured light scanner. This option offered both superior accuracy and convenience and was more cost effective.

In order for inhaled corticosteroids to be delivered adequately to the airways they require patients to take them regularly using an effective technique. Patients often have a poor inhaler technique, and this has been shown to result in sub-optimal asthma control. It is important for all clinicians prescribing inhaled medication to be experienced in the correct technique, and take time to train children so that they have mastered corrected inhaler technique. Using Teach to Goal or teach back methodology is a simple and effective way to provide this in the clinic setting. More than one training session is typically needed before children can master correct inhaler technique. Adherence to inhaled therapy has been shown to be sub-optimal in pediatric populations, with studies showing an average rate of around 50%. Subjective methods of measuring adherence have been shown to be inaccurate and overestimate rates. The advent of new technology has allowed adherence rates to be measured electronically, and it has been shown that regular feedback of these data can be effective at improving asthma control. New mobile apps and smart technology aim to engage patients and families with their asthma care. Effective use of these apps in collaboration with health care professionals has a vast potential to improve adherence rates and inhaler technique, resulting in improved asthma control.

ObjectiveTo evaluate the success rates of home cardiorespiratory polygraphy in children under investigation for sleep-disordered breathing and parent perspectives on equipment use at home.DesignProspective observational study.SettingSheffield, Evelina London and Southampton Children’s Hospitals.PatientsData are reported for 194 research participants with Down syndrome, aged 0.5–5.9 years across the three centres and 61 clinical patients aged 0.4–19.5 years from one centre, all of whom had home cardiorespiratory polygraphy including respiratory movements, nasal pressure flow, pulse oximetry, body position and motion.Main outcome measuresPercentage of home cardiorespiratory studies successfully acquiring ≥4 hours of artefact-free data at the first attempt. Parental report of ease of use of equipment and preparedness to repeat home diagnostics in the future.Results143/194 (74%; 95% CI 67% to 79%) of research participants and 50/61 (82%; 95% CI 71% to 90%) of clinical patients had successful home cardiorespiratory polygraphy at the first attempt. Some children required multiple attempts to achieve a successful study. Overall, this equated to 1.3 studies per research participant and 1.2 studies per clinical child. The median artefact-free sleep time for successful research studies was 515 min (range 261–673) and for clinical studies 442 min (range 291–583). 84% of research and 87% of clinical parents expressed willingness to repeat home cardiorespiratory polygraphy in the future. 67% of research parents found the equipment ‘easy or okay’ to use, while 64% of clinical parents reported it as ‘easy’ or ‘very easy’.ConclusionsHome cardiorespiratory polygraphy offers an acceptable approach to the assessment of sleep-disordered breathing in children.

BackgroundThere is uncertainty about the most appropriate ways to manage non-respiratory sleep disturbances in children with neurodisabilities (NDs).ObjectiveTo assess the clinical effectiveness and safety of NHS-relevant pharmacological and non-pharmacological interventions to manage sleep disturbance in children and young people with NDs, who have non-respiratory sleep disturbance.Data sourcesSixteen databases, including The Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE, were searched up to February 2017, and grey literature searches and hand-searches were conducted.Review methodsFor pharmacological interventions, only randomised controlled trials (RCTs) were included. For non-pharmacological interventions, RCTs, non-randomised controlled studies and before-and-after studies were included. Data were extracted and quality assessed by two researchers. Meta-analysis and narrative synthesis were undertaken. Data on parents’ and children’s experiences of receiving a sleep disturbance intervention were collated into themes and reported narratively.ResultsThirty-nine studies were included. Sample sizes ranged from 5 to 244 participants. Thirteen RCTs evaluated oral melatonin. Twenty-six studies (12 RCTs and 14 before-and-after studies) evaluated non-pharmacological interventions, including comprehensive parent-directed tailored (n = 9) and non-tailored (n = 8) interventions, non-comprehensive parent-directed interventions (n = 2) and other non-pharmacological interventions (n = 7). All but one study were reported as having a high or unclear risk of bias, and studies were generally poorly reported. There was a statistically significant increase in diary-reported total sleep time (TST), which was the most commonly reported outcome for melatonin compared with placebo [pooled mean difference 29.6 minutes, 95% confidence interval (CI) 6.9 to 52.4 minutes;p = 0.01]; however, statistical heterogeneity was extremely high (97%). For the single melatonin study that was rated as having a low risk of bias, the mean increase in TST was 13.2 minutes and the lower CI included the possibility of reduced sleep time (95% CI –13.3 to 39.7 minutes). There was mixed evidence about the clinical effectiveness of the non-pharmacological interventions. Sixteen studies included interventions that investigated the feasibility, acceptability and/or parent or clinician views of sleep disturbance interventions. The majority of these studies reported the ‘family experience’ of non-pharmacological interventions.LimitationsPlanned subgroup analysis was possible in only a small number of melatonin trials.ConclusionsThere is some evidence of benefit for melatonin compared with placebo, but the degree of benefit is uncertain. There are various types of non-pharmacological interventions for managing sleep disturbance; however, clinical and methodological heterogeneity, few RCTs, a lack of standardised outcome measures and risk of bias means that it is not possible to draw conclusions with regard to their effectiveness. Future work should include the development of a core outcome, further evaluation of the clinical effectiveness and cost-effectiveness of pharmacological and non-pharmacological interventions and research exploring the prevention of, and methods for identifying, sleep disturbance. Research mapping current practices and exploring families’ understanding of sleep disturbance and their experiences of obtaining help may facilitate service provision development.Study registrationThis study is registered as PROSPERO CRD42016034067.FundingThe National Institute for Health Research Health Technology Assessment programme.

ObjectivesTo assess whether a core outcome set is required for studies evaluating the effectiveness of interventions for non-respiratory sleep disturbances in children with neurodisabilities.DesignSurvey of outcome measures used in primary studies identified by a systematic review.Data sourcesASSIA, CENTRAL, Cochrane Database of Systematic Reviews, Conference Proceedings Citation Index, CINAHL, DARE, Embase, HMIC, MEDLINE, MEDLINE In-Process, PsycINFO, Science Citation Index, Social Care Online, Social Policy & Practice, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform and the UK Clinical Trials Gateway were searched up to February 2017.Eligibility criteriaStudies evaluating pharmacological or non-pharmacological interventions for children (≤18 years old) with a neurodisability and experiencing non-respiratory sleep disturbance.Data extraction and synthesisOutcome measures were listed from each study and categorised into domains.ResultsThirty-nine studies assessed five core outcome areas: child sleep, other child outcomes, parent outcomes, adverse events and process measures. There were 54 different measures of child sleep across five domains: global measures; sleep initiation; maintenance; scheduling; and other outcomes. Fifteen non-pharmacological (58%) and four pharmacological studies (31%) reported child outcomes other than sleep using 29 different measures.One pharmacological and 14 non-pharmacological (54%) studies reported parent outcomes (17 different measures). Eleven melatonin studies (85%) recorded adverse events, with variation in how data were collected and reported. One non-pharmacological study reported an explicit method of collecting on adverse events. Several process measures were reported, related to adherence, feasibility of delivery, acceptability and experiences of receiving the intervention.ConclusionsThere is a lack of consistency between studies in the outcome measures used to assess the effectiveness of interventions for non-respiratory sleep disturbances in children with neurodisabilities. A minimum core outcome set, with international consensus, should be developed in consultation with parents, children and young people, and those involved in supporting families.PROSPERO registration numberCRD42016034067

AimsWe describe how patient and public involvement (PPI) was integrated into the design of an intervention for a randomised controlled trial (RCT) based within primary care. The RCT, known as the PLEASANT trial, aimed to reduce unscheduled medical contacts in children with asthma associated with start of the new school year in September with a simple postal intervention, highlighting the importance of maintaining asthma medication for helping to prevent increased asthma exacerbations.BackgroundPPI is a key feature of UK health research policy, and is often a requirement of funding from the National Institute for Health Research. There are few detailed accounts of PPI in the design and conduct of clinical trials in the PPI literature for researchers to learn from.MethodsWe held PPI consultation events to determine whether the proposed intervention for the trial was acceptable to children with asthma and their parents, and to ascertain whether enhancements should be made. Two PPI consultation events were held with children with asthma and their parents, prior to the research commencing. Detailed field notes were taken by the research team at each consultation event.FindingsAt the first consultation event, parents and children endorsed the trial’s rationale, made suggestions to the wording of the trial intervention letter, and made recommendations about to whom the letter should be sent out. At the second consultation event, parents discussed the timing of the intervention, commented on the lay summary of the Research Ethics Application, and were invited to join the trial’s steering committee, while the children selected a logo for the study. PPI has resulted in enhancements to the PLEASANT study’s intervention. A further PPI consultation event is scheduled for the end of the trial, in order for children with asthma and their parents to contribute to the trial’s dissemination strategy.

Background: Respiratory rate is a vital physiological measurement used in the immediate assessment of unwell children and adults. Convenient electronic devices exist for the measurement of pulse, blood pressure, oxygen saturation, and temperature. Although devices which measure respiratory rate exist, none have entered everyday clinical practice for acute assessment of children and adults. An accurate and practical device which has no physical contact with the patient is important to ensure readings are not affected by distress caused by the assessment method. Objective: The aim of this study was to evaluate the use of a thermal imaging method to monitor the respiratory rate in children and adults. Methods: Facial thermal images of adult volunteers and children undergoing elective polysomnography were included. Respiration was recorded for at least 2 min with the camera positioned 1 m from the subject’s face. Values obtained using the thermal imaging camera were compared with those obtained from contact methods such as the nasal thermistor, respiratory inductance plethysmography, nasal airflow, and end tidal CO2. Results: A total of 61 subjects, including 41 adults (age range 27–46 years) and 20 children (age range 0.5–18 years) were enrolled. The correlation between the respiratory rate measured using thermal imaging and the contact method was r = 0.94. Sequential refinements to the thermal imaging algorithms resulted in the ability to perform real-time measurements and an improvement of the correlation to r = 0.995. Conclusion: This exploratory study shows that thermal imaging-derived respiratory rates in children and adults correlate closely with the best performing standard method. With further refinements, this method could be implemented in both acute and chronic care in children and adults.

Aim To evaluate the effectiveness of pharmacological interventions for managing non‐respiratory sleep disturbances in children with neurodisabilities. Method We performed a systematic review and meta‐analyses of randomized controlled trials (RCTs). We searched 16 databases, grey literature, and reference lists of included papers up to February 2017. Data were extracted and assessed for quality by two researchers (B.B., C.M., G.S., A.S., A.P.). Results Thirteen trials were included, all evaluating oral melatonin. All except one were at high or unclear risk of bias. There was a statistically significant increase in diary‐reported total sleep time for melatonin compared with placebo (pooled mean difference 29.6min, 95% confidence interval [CI] 6.9–52.4, p=0.01). Statistical heterogeneity was high (97%). For the single RCT with low risk of bias, the unadjusted mean difference in total sleep time was 13.2 minutes (95% CI −13.3 to 39.7) favouring melatonin, while the mean difference adjusted for baseline total sleep time was statistically significant (22.4min, 95% CI 0.5–44.3, p=0.04). Adverse event profile suggested that melatonin was well‐tolerated. Interpretation There is a paucity of evidence on managing sleep disturbances in children with neurodisabilities, and it is mostly of limited scope and poor quality. There is evidence of the benefit and safety of melatonin compared with placebo, although the extent of this benefit is unclear. What this paper adds Melatonin for the management of non‐respiratory sleep disturbances in children with neurodisabilities was well tolerated with minimal adverse effects.The extent of benefit and which children might benefit most from melatonin use is uncertain.Benefit may be greatest in those with autism spectrum disorder; however, this finding should be interpreted with caution., What this paper adds Melatonin for the management of non‐respiratory sleep disturbances in children with neurodisabilities was well tolerated with minimal adverse effects.The extent of benefit and which children might benefit most from melatonin use is uncertain.Benefit may be greatest in those with autism spectrum disorder; however, this finding should be interpreted with caution. This article's abstract has been translated into Spanish and Portuguese. Follow the links from the abstract to view the translations.

Aim To describe existing evidence on non-pharmacological interventions to manage sleep disturbance in children with neurodisabilities. Method We systematically reviewed non-pharmacological interventions aimed at improving non-respiratory sleep disturbance in children with neurodisability. Sixteen databases, grey literature, and reference lists of included papers were searched up to February 2017. Two researchers (B.B., C.M., G.S., A.S., A.P.) undertook screening, data extraction, and quality appraisal. Results Twenty-five studies were included: 11 randomized controlled trials and 14 before-and-after studies. All studies were at high or unclear risk of bias. Parent-directed interventions were categorized as comprehensive tailored interventions (n=9), comprehensive non-tailored interventions (n=8), and non-comprehensive interventions (n=2). Six 'other' non-pharmacological interventions were included. Seventy-one child and parent sleep-related outcomes were measured across the included studies. We report the two most commonly measured outcomes: the Child Sleep Habits Questionnaire and sleep onset latency. Five studies reported significant improvements on at least one of these outcomes. Interpretation Various types of non-pharmacological intervention for managing sleep disturbance have been evaluated. Clinical heterogeneity and poor study quality meant we could not draw definitive conclusions on the effectiveness of these interventions. Current clinical guidance recommends parent-directed interventions as the first approach to managing sleep disturbance; prioritizing research in this area is recommended. What this paper adds Existing evidence on non-pharmacological interventions to manage sleep disturbance in children with neurodisabilities is predominately of poor quality. Most included studies evaluated parent-directed interventions of varying content and intensity. There was very little consistency between studies in the outcome measures used. There is some evidence that parent-directed interventions may improve child outcomes.

Objective Children with Down syndrome are at high risk of obstructive sleep apnoea (OSA) and screening is recommended. Diagnosis of OSA should be confirmed with multichannel sleep studies. We aimed to determine whether home pulse oximetry (HPO) discriminates children at high risk of OSA, who need further diagnostic multichannel sleep studies.Design Cross-sectional prospective study in a training sample recruited through three UK centres. Validation sample used single-centre retrospective analysis of clinical data.Patients Children with Down syndrome aged 0.5–6 years.Intervention Diagnostic multichannel sleep study and HPO.Main outcome measures Sensitivity and specificity of HPO to predict moderate-to-severe OSA.Results 161/202 children with Down syndrome met quality criteria for inclusion and 25 had OSA. In this training sample, the best HPO parameter predictors of OSA were the delta 12 s index >0.555 (sensitivity 92%, specificity 65%) and 3% oxyhaemoglobin (SpO2) desaturation index (3% ODI)>6.15 dips/hour (sensitivity 92%, specificity 63%). Combining variables (delta 12 s index, 3% ODI, mean and minimum SpO2) achieved sensitivity of 96% but reduced specificity to 52%. All predictors retained or improved sensitivity in a clinical validation sample of 50 children with variable loss of specificity, best overall was the delta 12 s index, a measure of baseline SpO2 variability (sensitivity 92%; specificity 63%). Conclusions HPO screening could halve the number of children with Down syndrome needing multichannel sleep studies and reduce the burden on children, families and health services alike. This approach offers a practical universal screening approach for OSA in Down syndrome that is accessible to the non-specialist paediatrician.

BackgroundAsthma episodes and deaths are known to be seasonal. A number of reports have shown peaks in asthma episodes in school-aged children associated with the return to school following the summer vacation. A fall in prescription collection in the month of August has been observed, and was associated with an increase in the number of unscheduled contacts after the return to school in September.ObjectiveThe primary objective of the study was to assess whether or not a NHS-delivered public health intervention reduces the September peak in unscheduled medical contacts.DesignCluster randomised trial, with the unit of randomisation being 142 NHS general practices, and trial-based economic evaluation.SettingPrimary care.InterventionA letter sent (n = 70 practices) in July from their general practitioner (GP) to parents/carers of school-aged children with asthma to remind them of the importance of taking their medication, and to ensure that they have sufficient medication prior to the start of the new school year in September. The control group received usual care.Main outcome measuresThe primary outcome measure was the proportion of children aged 5–16 years who had an unscheduled medical contact in September 2013. Supporting end points included the proportion of children who collected prescriptions in August 2013 and unscheduled contacts through the following 12 months. Economic end points were quality-adjusted life-years (QALYs) gained and costs from an NHS and Personal Social Services perspective.ResultsThere is no evidence of effect in terms of unscheduled contacts in September. Among children aged 5–16 years, the odds ratio (OR) was 1.09 [95% confidence interval (CI) 0.96 to 1.25] against the intervention. The intervention did increase the proportion of children collecting a prescription in August (OR 1.43, 95% CI 1.24 to 1.64) as well as scheduled contacts in the same month (OR 1.13, 95% CI 0.84 to 1.52). For the wider time intervals (September–December 2013 and September–August 2014), there is weak evidence of the intervention reducing unscheduled contacts. The intervention did not reduce unscheduled care in September, although it succeeded in increasing the proportion of children collecting prescriptions in August as well as having scheduled contacts in the same month. These unscheduled contacts in September could be a result of the intervention, as GPs may have wanted to see patients before issuing a prescription. The economic analysis estimated a high probability that the intervention was cost-saving, for baseline-adjusted costs, across both base-case and sensitivity analyses. There was no increase in QALYs.LimitationThe use of routine data led to uncertainty in the coding of medical contacts. The uncertainty was mitigated by advice from a GP adjudication panel.ConclusionsThe intervention did not reduce unscheduled care in September, although it succeeded in increasing the proportion of children both collecting prescriptions and having scheduled contacts in August. After September there is weak evidence in favour of the intervention. The intervention had a favourable impact on costs but did not demonstrate any impact on QALYs. The results of the trial indicate that further work is required on assessing and understanding adherence, both in terms of using routine data to make quantitative assessments, and through additional qualitative interviews with key stakeholders such as practice nurses, GPs and a wider group of children with asthma.Trial registrationCurrent Controlled Trials ISRCTN03000938.Funding detailsThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 93. See the HTA programme website for further project information.

Background Suboptimal adherence to inhaled steroids is common in children with asthma and is associated with poor disease control, reduced quality of life and even death. Previous studies using feedback of electronically monitored adherence data have demonstrated improved adherence, but have not demonstrated a significant impact on clinical outcomes. The aim of this study was to determine whether introduction of this approach into routine practice would result in improved clinical outcomes. Methods Children with asthma aged 6–16 years were randomised to the active intervention consisting of electronic adherence monitoring with daily reminder alarms together with feedback in the clinic regarding their inhaled corticosteroid (ICS) use or to the usual care arm with adherence monitoring alone. All children had poorly controlled asthma at baseline, taking ICS and long-acting β-agonists. Subjects were seen in routine clinics every 3 months for 1 year. The primary outcome was the Asthma Control Questionnaire (ACQ) score. Secondary outcomes included adherence and markers of asthma morbidity. Results 77 of 90 children completed the study (39 interventions, 38 controls). Adherence in the intervention group was 70% vs 49% in the control group (p≤0.001). There was no significant difference in the change in ACQ, but children in the intervention group required significantly fewer courses of oral steroids (p=0.008) and fewer hospital admissions (p≤0.001). Conclusions The results indicate that electronic adherence monitoring with feedback is likely to be of significant benefit in the routine management of poorly controlled asthmatic subjects. Trial registration number [NCT02451709][1]; pre-result. [1]: http://www.clinicaltrials.gov

Nonantimicrobial effects of antibiotics may contribute to their activity in the treatment of infective airway disease. The aim of this study was to identify antibiotics used for the treatment of infection in cystic fibrosis that may alter the activity of human neutrophil elastase (HNE) and Pseudomonas aeruginosa elastase (PE). The effect of antibiotics on the activity of purified HNE and PE, and HNE in sputum was assessed using colourimetric and fluorescent substrate assays by kinetic measurements, and by examining the interaction of HNE with inhibitors. Ceftazidime, tobramycin, and gentamycin slightly inhibited purified HNE activity whereas erythromycin and colistin significantly stimulated purified HNE and PE (395 and 557%, respectively). However, only colistin increased HNE activity in sputum (+102%) and was therefore studied in more detail. This increase in activity was not due an interference with the specific inhibition of HNE by α 1 -antitrypsin but colistin was found to reverse the inhibitory effects of small molecular weight molecules like heparin. Colistin increases the activity of human neutrophil elastase and Pseudomonas aeruginosa elastase, two proteases that contribute to the pathogenesis of cystic fibrosis airway disease.

Adherence to inhaled steroids is suboptimal in many children with asthma and can lead to poor disease control. Many previous studies in paediatric populations have used subjective and inaccurate adherence measurements, reducing their validity. Adherence studies now often use objective electronic monitoring, which can give us an accurate indication of the extent of non-adherence in children with asthma. A review of the studies using electronic adherence monitoring shows that half of them report mean adherence rates of 50% or below, and the majority report rates below 75%. Reasons for non-adherence are both intentional and non-intentional, incorporating illness perceptions, medication beliefs and practical adherence barriers. Interventions to improve adherence in the paediatric population have had limited success, with the most effective containing both educational and behavioural aspects.

Background: Within the UK, during September, there is a pronounced increase in the number of unscheduled medical contacts by school-aged children (4–16 years) with asthma. It is thought that that this might be caused by the return back to school after the summer holidays, suddenly mixing with other children again and picking up viruses which could affect their asthma. There is also a drop in the number of prescriptions administered in August. It is possible therefore that children might not be taking their medication as they should during the summer contributing to them becoming ill when they return to school. It is hoped that a simple intervention from the GP to parents of children with asthma at the start of the summer holiday period, highlighting the importance of maintaining asthma medication can help prevent increased asthma exacerbation, and unscheduled NHS appointments, following return to school in September. Methods/design: PLEASANT is a cluster randomised trial. A total of 140 General Practices (GPs) will be recruited into the trial; 70 GPs randomised to the intervention and 70 control practices of “usual care”. An average practice is expected to have approximately 100 children (aged 4–16 with a diagnosis of asthma) hence observational data will be collected on around 14000 children over a 24-month period. The Clinical Practice Research Datalink will collect all data required for the study which includes diagnostic, prescription and referral data. Discussion: The trial will assess whether the intervention can reduce exacerbation of asthma and unscheduled medical contacts in school-aged children associated with the return to school after the summer holidays. It has the potential to benefit the health and quality of life of children with asthma while also improving the effectiveness of NHS services by reducing NHS use in one of the busiest months of the year. An exploratory health economic analysis will gauge any cost saving associated with the intervention and subsequent impacts on quality of life. If results for the intervention are positive it is hoped that this could be adopted as part of routine care management of childhood asthma in general practice. Trial registration: Current controlled trials: ISRCTN03000938 (assigned 19/10/12) http://www.controlled-trials.com/ ISRCTN03000938/. UKCRN ID: 13572