Current advances and gaps in knowledge on personalizing masks for non-invasive respiratory support: a scoping review.

Non-invasive respiratory support delivered through a face mask has become a cornerstone treatment for adults and children with acute or chronic respiratory failure. However, an imperfect mask fit using commercially available interfaces is frequently encountered, which may result in patient discomfort and treatment inefficiency or failure. To overcome this challenge, over the last decade increasing attention has been given to the development of personalized face masks, which are custom made to address the specific facial dimensions of an individual patient. With this scoping review we aim to provide a comprehensive overview of the current advances and gaps in knowledge regarding the personalization of ventilation masks. We performed a systematic search of the literature, and identified and summarized a total of 23 studies. Most studies included were involved in the development of nasal masks. Studies targeting adult respiratory care mainly focused on chronic (home) ventilation and included some clinical testing in a relevant subject population. In contrast, pediatric studies focused mostly on respiratory support in the acute setting, while testing was limited to bench or case studies only. Most studies were positive regarding the performance (i.e. comfort, level of air leak and mask pressure applied to the skin) of personalized masks in bench testing or in human, healthy or patient, subjects. Advances in the field of 3D scanning and soft material printing were identified, but important gaps in knowledge remain. In particular, more insight into cushion materials, headgear design, clinical feasibility and cost-effectiveness is needed, before definite recommendations can be made regarding implementation of large scale clinical programs that personalize non-invasive respiratory support masks for adults and children.

Review of implementation models for children's sleep support services in the UK.

Sleep deprivation has a serious impact on physical and mental health. Children with neurodevelopmental disorders are frequently affected by chronic insomnia, defined as difficulty in either initiating sleep, maintaining sleep continuity or poor sleep quality which can lead to long-term detrimental effects on behaviour, learning and development.Interventions to address chronic insomnia in children include both pharmacological and non-pharmacological approaches. While some children unequivocally benefit from pharmacological treatment, recommendations suggest an intervention based on cognitive-behavioural techniques involving a thorough assessment of the child's sleep pattern, environment and psychosocial factors supporting the child to learn to self-soothe as first-line treatment. Evidence from sleep clinics delivered by trained community practitioners supports the efficacy of an intensive programme, whereby education, practical advice and follow-up support were key factors; however, these services are inconsistently resourced. In practice, sleep support interventions range from verbal advice given in clinics to healthy sleep leaflets to tailored and non-tailored parent-directed interventions. Delivery models include promotion of safe sleep within a wider health promotion context and targeted early intervention within sleep clinics delivered in health and community services or by the third sector but evidence for each model is lacking.We describe a comprehensive whole systems city-wide model of sleep support, ranging from awareness raising, universal settings, targeted support for complex situations to specialist support, delivered according to complexity and breadth of need. By building capacity and quality assurance into the existing workforce, the service has been sustainable and has continued to develop since its initial implementation in 2017. With increasing access to specialist sleep services across the UK, this model could become a widely generalisable approach for delivery of sleep services to children in the UK and lead to improved outcomes in those with severe sleep deprivation.

Changes in UK paediatric long-term ventilation practice over 10 years.

OBJECTIVES: To provide up-to-date information on the use of long-term ventilation (LTV) in the UK paediatric population and to compare the results with data collected 10 and 20 years previously. DESIGN: A single timepoint census completed by LTV centres in the UK, carried out via an online survey. SETTING AND PATIENTS: All patients attending paediatric LTV services in the UK. RESULTS: Data were collected from 25 LTV centres in the UK. The total study population was 2383 children and young people, representing a 2.5-fold increase in the last 10 years. The median age was 9 years (range 0-20 years). Notable changes since 2008 were an increase in the proportion of children with central hypoventilation syndrome using mask ventilation, an increase in overall numbers of children with spinal muscular atrophy (SMA) type 1, chronic lung disease of prematurity and cerebral palsy being ventilated, and a 4.2-fold increase in children using LTV for airway obstruction. The use of 24-hour ventilation, negative pressure ventilation and tracheostomy as an interface had declined. 115 children had received a disease-modifying drug. The use of ataluren and Myozyme did not influence the decision to treat with LTV, but in 35% of the children with SMA type 1 treated with nusinersin, the clinician stated that the use of this drug had or may have influenced their decision to initiate LTV. CONCLUSION: The results support the need for national database for children and young people using LTV at home to inform future recommendations and assist in resource allocation planning.

The (extended) achondroplasia foramen magnum score has good observer reliability.

BACKGROUND: Achondroplasia is the most common skeletal dysplasia. A significant complication is foramen magnum stenosis. When severe, compression of the spinal cord may result in sleep apnea, sudden respiratory arrest and death. To avoid complications, surgical decompression of the craniocervical junction is offered in at-risk cases. However, practice varies among centres. To standardize magnetic resonance (MR) reporting, the achondroplasia foramen magnum score was recently developed. The reliability of the score has not been assessed. OBJECTIVE: To assess the interobserver reliability of the achondroplasia foramen magnum score. MATERIALS AND METHODS: Base of skull imaging of children with achondroplasia under the care of Sheffield Children's Hospital was retrospectively and independently reviewed by four observers using the achondroplasia foramen magnum score. Two-way random-effects intraclass coefficient (ICC) was used to assess inter- and intra-observer reliability. RESULTS: Forty-nine eligible cases and five controls were included. Of these, 10 were scored normal, 17 had a median score of 1 (mild narrowing), 11 had a median score of 2 (effacement of cerebral spinal fluid), 10 had a score of 3 (compression of cord) and 6 had a median score of 4 (cord myelopathic change). Interobserver ICC was 0.72 (95% confidence interval = 0.62-0.81). Intra-observer ICC ranged from 0.60 to 0.86. Reasons for reader disagreement included flow void artefact, subtle T2 cord signal and myelopathic T2 cord change disproportionate to canal narrowing. CONCLUSION: The achondroplasia foramen magnum score has good interobserver reliability. Imaging features leading to interobserver disagreement have been identified. Further research is required to prospectively validate the score against clinical outcomes.

Paediatric narcolepsy: a review of diagnosis and management.

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.

Custom-made 3D printed masks for children using non-invasive ventilation: a comparison of 3D scanning technologies and specifications for future clinical service use, guided by patient and professional experience.

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.

Pseudomonas aeruginosa infection in respiratory samples in children with neurodisability-to treat or not to treat?

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 (p<0.05). In 52% samples, multiple pathogens co-existed. There was no significant association between choice of antibiotic and clinical outcome but when antibiotics were changed to specific PA antibiotics during the course of the illness, all resulted in clinical improvement. Twenty-six episodes involving 8 patients with recurrent admissions involved PA organisms that were resistant to one or more antibiotics.Conclusions: 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.

Aerosol Therapy in Asthma-Why We Are Failing Our Patients and How We Can Do Better.

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.

Custom-made 3D printed masks for children using non-invasive ventilation: a feasibility study of production method and testing of outcomes in adult volunteers.

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.

Psychometric Properties and Predictive Value of a Screening Questionnaire for Obstructive Sleep Apnea in Young Children With Down Syndrome.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is common in children with Down syndrome (DS) and is associated with adverse health and cognitive outcomes. Daytime clinical assessment is poorly predictive of OSA, so regular screening with sleep studies is recommended. However, sleep studies are costly and not available to all children worldwide. We aimed to evaluate the psychometric properties and predictive value of a newly developed screening questionnaire for OSA in this population. METHODS: 202 children aged 6 months to 6th birthday with DS were recruited, of whom 188 completed cardio-respiratory sleep studies to generate an obstructive apnea hypopnea index (OAHI). Parents completed the 14-item Down syndrome OSA screening questionnaire. Responses were screened, a factor analysis undertaken, internal consistency calculated and receiver operator characteristic (ROC) curves drawn to generate an area under the curve (AUC) to assess criterion related validity. RESULTS: Of 188 children who completed cardiorespiratory sleep studies; parents completed the screening questionnaire for 186. Of this study population 15.4% had moderate to severe OSA defined by an OAHI of ≥5/h. Sixty-three (33.9%) participants were excluded due to "unsure" responses or where questions were not answered. Using the remaining 123 questionnaires a four-factor solution was found, with the 1st factor representing breathing related symptoms, explaining a high proportion of the variance. Internal consistency was acceptable with a Cronbach alpha of 0.87. ROC curves for the total score generated an AUC statistic of 0.497 and for the breathing subscale an AUC of 0.603 for moderate to severe OSA. CONCLUSION: A well designed questionnaire with good psychometric properties had limited predictive value to screen for moderate to severe OSA in young children with DS. The use of a screening questionnaire is not recommended. Screening for OSA in this population requires objective sleep study measures.

Pilot study of an integrated model of sleep support for children: a before and after evaluation.

OBJECTIVE: Despite the success of behavioural sleep support interventions in the third sector, sleep support is not universally available for families in the UK. The aim of the study was to provide evidence of efficacy and to propose a delivery model for integrated sleep support for families of vulnerable children. DESIGN AND SETTING: A sleep support intervention was carried out in Sheffield Local Authority evaluated using a preintervention and postintervention study design by Sheffield Children's National Health Service (NHS) Trust. PARTICIPANTS: Fifty-six children aged 6-16 years with significant sleep problems were recruited; 39 completed the intervention and evaluation. INTERVENTIONS: Basic sleep education and an individualised programme was delivered by a sleep practitioner. Follow-on telephone support was provided to empower the parent (and/or young person) to carry out the sleep programme at home. An integrated NHS and Local Authority delivery model was designed and implemented. RESULTS: Parents' ratings of their child's ability to self-settle improved from 1.1/10 to 6.4/10 (p<0.05). Mean Warwick-Edinburgh Mental Well-being Scale scores improved significantly for parents/carers (MD 5.16, 95%CIs 2.62 to 7.69, p<0.05). Children who completed the intervention gained on average an extra 2.4 hours sleep a night. There was reduction in healthcare utilisation, illnesses and medication use. CONCLUSIONS: The behavioural approach to sleep support for these vulnerable groups of children is highly effective. Follow-on individual support to empower parents is key to achieving success. Sleep support can be implemented in NHS and Local Authority services by integration into the existing workforce using a cross-agency model.

Exploratory Study to Evaluate Respiratory Rate Using a Thermal Imaging Camera.

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.

Cardiorespiratory sleep studies at home: experience in research and clinical cohorts.

OBJECTIVE: To evaluate the success rates of home cardiorespiratory polygraphy in children under investigation for sleep-disordered breathing and parent perspectives on equipment use at home. DESIGN: Prospective observational study. SETTING: Sheffield, Evelina London and Southampton Children's Hospitals. PATIENTS: Data 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 MEASURES: Percentage 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. RESULTS: 143/194 (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'. CONCLUSIONS: Home cardiorespiratory polygraphy offers an acceptable approach to the assessment of sleep-disordered breathing in children.

Home oximetry to screen for obstructive sleep apnoea in Down syndrome.

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.

Investigating the feasibility of text message reminders to improve adherence to nebulized medication in children and adolescents with cystic fibrosis.

BACKGROUND: Children with cystic fibrosis (CF) often have suboptimal adherence rates to nebulized medication. Adherence barriers cited include forgetting to take the nebulizers, due to busy home and social lives. Text message reminders have been shown to be effective at improving adherence rates in other chronic diseases such as asthma and diabetes. OBJECTIVE: The objective of this study was to assess the feasibility and efficacy of sending text reminders for a prolonged period of time to children with CF. MATERIALS AND METHODS: Children with CF aged 5-16 years taking at least one medication via a nebulizer with an electronic adherence monitor were consented for the study. Text message reminders were sent to participants and/or parents via the hospital's automated text service, up to twice a day, for 6 months. The adherence rates for the 6-month text period were compared to the previous 6 months before the study. Rates were calculated for weekdays, weekends, and school holidays. RESULTS: Seventeen participants were recruited to the study, with a mean age of 12 years and a mean forced expiratory volume in 1 second (FEV1) of 81% predicted. Fifteen children completed the 6-month text period, and I-neb data were accurately analyzed for 13 participants. The mean adherence rate in the 6 months receiving texts was 80%, compared to 81% in the prior 6 months. Overall adherence rates on weekdays, weekends, and school holidays were equivalent during the 2 time periods. A subgroup of patients with moderate baseline adherence showed increased adherence during the text period, particularly at weekends. CONCLUSION: It is feasible to send text message reminders to children with CF, and they are amenable to this approach. Although text reminders do not increase rates in patients with existing optimal adherence, they may be of value in patients with more moderate baseline rates.

Poor inter-observer agreement in the measurement of respiratory rate in children: a prospective observational study.

OBJECTIVE: To determine the inter-observer agreement of a respiratory rate (RR) count on a child when assessed by three independent observers. DESIGN: The RR of 169 children (age range: 3 days to 15 years) was measured by three independent observers over a 3-month period. The first RR was taken by different healthcare professionals (HCPs) from within the hospital using their own preferred method of measurement. A further count of RR was then taken by two observers from the research team simultaneously within 30 min of the first measurement, using the WHO-recommended method of measurement. RESULTS: 507 RR measurements were taken on 169 children. Median RR showed a 4 beats per minute (bpm) difference between the HCP (median RR 32 bpm) and the researchers (median RR 28 bpm). The 95% limits of agreement between the first measurement and second and third measurements were -10.2 to 17.7 bpm and -11.4 to 18.7 bpm, respectively. For simultaneous measurements, the 95% limits of agreement were -7.1 to 7.0 bpm. 81 children had a RR > 95th centile for their age and an even poorer level of agreement was seen in these children than in those whose RR was within normal range. In only 27 of these 81 children (33%) did all three observers agree on the presence of a raised RR. CONCLUSIONS: Inter-observer agreement for the measurement of RR in children is poor. The effect that this variation has on the clinical assessment and subsequent management of a child may be significant. These findings highlight the need for a robust review of our current measurement methods and interpretation of an important vital sign.

STAAR: a randomised controlled trial of electronic adherence monitoring with reminder alarms and feedback to improve clinical outcomes for children with asthma.

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 ß-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; pre-result.

Single versus combination intravenous anti-pseudomonal antibiotic therapy for people with cystic fibrosis.

BACKGROUND: Choice of antibiotic, and the use of single or combined therapy are controversial areas in the treatment of respiratory infection due to Pseudomonas aeruginosa in cystic fibrosis (CF). Advantages of combination therapy include wider range of modes of action, possible synergy and reduction of resistant organisms; advantages of monotherapy include lower cost, ease of administration and reduction of drug-related toxicity. Current evidence does not provide a clear answer and the use of intravenous antibiotic therapy in cystic fibrosis requires further evaluation. This is an update of a previously published review. OBJECTIVES: To assess the effectiveness of single compared to combination intravenous anti-pseudomonal antibiotic therapy for treating people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search of the Group's Trials Register: 14 October 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing a single intravenous anti-pseudomonal antibiotic with a combination of that antibiotic plus a second anti-pseudomonal antibiotic in people with CF. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: We identified 45 trials, of which eight trials (356 participants) comparing a single anti-pseudomonal agent to a combination of the same antibiotic and one other, were included.There was a wide variation in the individual antibiotics used in each trial. In total, the trials included seven comparisons of a beta-lactam antibiotic (penicillin-related or third generation cephalosporin) with a beta-lactam-aminoglycoside combination and three comparisons of an aminoglycoside with a beta-lactam-aminoglycoside combination. These two groups of trials were analysed as separate subgroups.There was considerable heterogeneity amongst these trials, leading to difficulties in performing the review and interpreting the results. The meta-analysis did not demonstrate any significant differences between monotherapy and combination therapy, in terms of lung function; symptom scores; adverse effects; and bacteriological outcome measures.These results should be interpreted cautiously. Six of the included trials were published between 1977 and 1988; these were single-centre trials with flaws in the randomisation process and small sample size. Overall, the methodological quality was poor. AUTHORS' CONCLUSIONS: The results of this review are inconclusive. The review raises important methodological issues. There is a need for an RCT which needs to be well-designed in terms of adequate randomisation allocation, blinding, power and long-term follow up. Results need to be standardised to a consistent method of reporting, in order to validate the pooling of results from multiple trials.