Therapeutic drug monitoring-guided dosing for pediatric cystic fibrosis patients: recent advances and future outlooks.

INTRODUCTION: Medicine use in children with cystic fibrosis (CF) is complicated by inconsistent pharmacokinetics at variance with the general population, a lack of research into this and its effects on clinical outcomes. In the absence of established dose regimens, therapeutic drug monitoring (TDM) is a clinically relevant tool to optimize drug exposure and maximize therapeutic effect by the bedside. In clinical practice though, use of this is variable and limited by a lack of expert recommendations. AREAS COVERED: We aimed to review the use of TDM in children with CF to summarize recent developments, current recommendations, and opportunities for future directions. We searched PubMed for relevant publications using the broad search terms "cystic fibrosis" in combination with the specific terms "therapeutic drug monitoring (TDM)" and "children." Further searches were undertaken using the name of identified drugs combined with the term "TDM." EXPERT OPINION: Further research into the use of Bayesian forecasting and the relationship between exposure and response is required to personalize dosing, with the opportunity for the development of expert recommendations in children with CF. Use of noninvasive methods of TDM has the potential to improve accessibility to TDM in this cohort.

Case series: propranolol liquid in the treatment of tachyarrhythmias in neonates and infants: potential for errors.

Oral propranolol therapy is commonly used for the prevention of tachyarrhythmias in infancy and childhood. Propranolol is commercially produced in four concentrations allowing varying volumes to be administered. However, quite often an alternative strength of propranolol liquid is issued without clear change in instructions or warning. This may lead to parents inadvertently administering the wrong dose.

Patient and family perceptions of the provision of medicines as part of virtual outpatient consultations for children during COVID-19 pandemic.

OBJECTIVES: To evaluate (1) views and perceptions of patients/parents/carers and healthcare professionals on the medicines optimisation (MO) process following virtual outpatient clinic (VOC) during the COVID-19 pandemic and (2) the processes introduced at this time, identifying areas for improvements and suggest potential solutions. DESIGN: A mixed-methods service evaluation using qualitative and quantitative methods of the MO pathway in children aged 0-18 years following VOC across three specialist children's units.Semi-structured interviews were conducted over the telephone with the participants exploring their experiences and categorised into themes.Process mapping sessions with the multidisciplinary team identified areas for improvement and an ease impact framework developed for potential solutions.Outcome measures included: (1) themes from interviews, (2) patients satisfaction rates, (3) process maps and (4) development of a simplified future process. RESULTS: One hundred and twenty-five patients' families were contacted: 71 families consented to participate and their views were categorised into four main themes: (1) patient experience, (2) communication, (3) need for virtual video consultations for patient education by hospital pharmacists and (4) need for electronic processes to send prescriptions to local pharmacies.Median patient satisfaction rate was 96% (range 67%-100%). The convenience of receiving medications directly to patient's homes; access to medicines information helplines and education provided by pharmacists were regarded as valuable. Communication between care providers, development of virtual video consultations by hospital pharmacists and electronic transfer of some prescriptions directly to community pharmacies were identified as areas of improvement. CONCLUSIONS: Participants appreciated the pharmacy processes adopted during the pandemic, however, challenges and recommendations for improvement in delivering MO VOC were identified. As digital innovations evolve within the NHS, future research should focus on integrated care and improved communication between care providers with selected medications prescribed directly to community pharmacies using electronic prescription service, with clinical screening and education provided by hospital pharmacists.

COVID-19 and delivery of difficult asthma services.

The COVID-19 pandemic necessitated an urgent reconfiguration of our difficult asthma (DA) service. We rapidly switched to virtual clinics and rolled out home spirometry based on clinical need. From March to August 2020, 110 patients with DA (68% virtually) were seen in clinic, compared with March-August 2019 when 88 patients were seen face-to-face. There was DA clinic cancellation/non-attendance (16% vs 43%; p<0.0003). In patients with home spirometers, acute hospital admissions (6 vs 26; p<0.01) from March to August 2020 were significantly lower compared with the same period in 2019. There was no difference in the number of courses of oral corticosteroids or antibiotics prescribed (47 vs 53; p=0.81). From April to August 2020, 50 patients with DA performed 253 home spirometry measurements, of which 39 demonstrated >20% decrease in forced expiratory volume in 1 s, resulting in new action plans in 87% of these episodes. In our DA cohort, we demonstrate better attendance rates at virtual multidisciplinary team consultations and reduced hospital admission rates when augmented with home spirometry monitoring.

Paediatric severe asthma biologics service: from hospital to home.

Children with severe asthma may be treated with biologic agents normally requiring 2-4 weekly injections in hospital. In March 2020, due to COVID-19, we needed to minimise hospital visits. We assessed whether biologics could be given safely at home. The multidisciplinary team identified children to be considered for home administration. This was virtually observed using a video link, and home spirometry was also performed. Feedback was obtained from carers and young people. Of 23 patients receiving biologics, 16 (70%) families agreed to homecare administration, 14 administered by parents/patients and 2 by a local nursing team. Video calls for omalizumab were observed on 56 occasions, mepolizumab on 19 occasions over 4 months (April-July). Medication was administered inaccurately on 2/75 occasions without any adverse events. Virtually observed home biologic administration in severe asthmatic children, supported by video calls and home spirometry, is feasible, safe and is positively perceived by children and their families.

Novel electronic adherence monitoring devices in children with asthma: a mixed-methods study.

INTRODUCTION: Adherence monitoring to inhaled corticosteroids is an essential component of asthma management. Electronic monitoring devices (EMD) provide objective data on date, time and number of actuations. However, most give no information on inhalation. Novel EMD (NEMD) platforms have the potential to monitor both activation and inhalation. AIM: To assess the feasibility of NEMDs, in terms of usability, acceptability to patients and healthcare professionals and accuracy. METHODS: This was an open-label, prospective, mixed-methods, pragmatic randomised study. Children with asthma attending specialist tertiary care were randomised to one of four NEMD: Remote Directly Observed Therapy (R-DOT), Hailie Smartinhaler, INhaler Compliance Assessment device (INCA) and the Rafi-tone App. Following monitoring, participants were invited to focus groups or one-to-one interviews. Usability and acceptability were evaluated using themes identified from the focus groups and interviews. Adherence accuracy was determined using adherence data from each NEMD. RESULTS: Thirty-five children were recruited; 18 (51%), (11 males, median age 13.5 (7-16) years) completed monitoring, 14 (78%) provided feedback. Participants identified various features such as ease of use and minimal effort as desirable criteria for an NEMD. The Hailie and INCA fulfilled these criteria and were able to record both actuation and inhalation. Negative themes included a 'Big Brother' effect and costs. CONCLUSION: There was no 'one size fits all', as participants identified advantages and disadvantages for each NEMD. Devices that can easily calculate adherence to activation and inhalation have the potential to have greatest utility in clinical practice. Each NEMD has different functionality and therefore choice of platform should be determined by the needs of the patient and healthcare professional.

Initiating Self-Administration of Medicines for inpatients with cystic fibrosis.

INTRODUCTION: Children with cystic fibrosis (CF) take a multitude of therapies at home. Self-Administration of Medicines (SAM) is a scheme whereby the parent/carer and/or older child keep control of their own medicines in hospital. We initiated a scheme and assessed drug errors, cost implications, and parent and nurse satisfaction. METHODS: Following a pilot stage, the SAM protocol was initiated and amended as necessary. Drug errors were analysed from the Datix hospital electronic reporting system. Cost analysis of use of the patents own drugs was carried out. Questionnaires were given to parents and nursing staff. RESULTS: In the initial 10 months, 97 children had 159 admissions, and 60% were deemed suitable for SAM. Drug errors still occurred-33 in 5 years. Cost savings for the hospital over 1 year were £20 022 for 123 admissions. Patient/parent satisfaction was high, and all wished to partake in SAM for further admissions. CONCLUSIONS: The scheme was a success although it took 3 years to bring to fruition. Drug errors still occurred but we were able to amend the protocol appropriately to react to these. Cost savings are an incidental benefit from use of patient's own medication. The SAM scheme is applicable to all children with chronic disease on long term medications when they are in hospital.

Prescribing emergency oral steroids in asthma clinics.

We retrospectively reviewed children who had been prescribed emergency oral corticosteroids (OCS) in a routine tertiary paediatric respiratory clinic appointment. We subsequently assessed adherence from prescription uptake of inhaled corticosteroids or combination inhalers in the 6 months prior to the episode. In 2 years, 25 children received 32 courses of prednisolone. Median adherence was 33%, but 28% for those with repeated OCS prescriptions. Prescribing acute OCS in a routine clinic is a red flag for potential poor adherence to preventer therapies, and may also indicate the child has poor perception of the severity of their symptoms. An assessment of adherence should be carried out and help given to the child and their family to improve poor adherence when detected.

SELF-ADMINISTRATION OF IN-PATIENT MEDICATIONS: A PILOT STUDY IN CHILDREN WITH CYSTIC FIBROSIS.

INTRODUCTION: Children with Cystic Fibrosis (CF) have complex medication regimens, where responsibility for administration usually lies with the parent/carer until the child is older and able to take over this role.1 On admission to hospital this role is usually undertaken by nurses, leaving patients/parents/carers feeling disempowered, and unprepared for discharge. AIMS: All CF admissions to be offered the Self-Administration Of Medicines Scheme (SAM).▸ Empower patients/parents/carers with responsibility of administering their own medications▸ Reduce nursing time▸ Educate patients/parents/carers about their medications▸ Cost-saving by utilising Patients Own Medicines (PODs). METHOD: A policy and training programme was developed and approved by the Trust's Medicines Management Board. This provided a framework for staff to use so that they may:▸ Obtain consent▸ Evaluate and re-use PODs▸ Safely store and obtain supplies▸ Continuously negotiate accountability for administration with patient/parent/carer.The study was conducted over a 10 month period, where all families with CF admitted, were assessed for participation in SAM. The nursing teams acted as the primary assessors for SAM and any concerns were referred to the paediatric CF multidisciplinary team. To evaluate the pilot, families were given questionnaires to establish their views about the scheme. Nurses were asked to feedback if SAM decreased time for medication administration. To evaluate the associated cost-saving, data on PODs suitable for re-use was collected. RESULTS: 159 children with CF were admitted to the ward, 95 (60%) were assessed to participate in the scheme and 64 (40%) of these did not join. Reasons for not joining included 32 (50%) short admissions, 13 (20%) refused, 5 (8%) patients were seriously ill and 14 (22%) had 'other' reasons. Those who joined the scheme received questionnaires and 31 (33%) of these were completed. All welcomed the scheme and stated that they would take part again with the main benefits cited as not needing to wait for nurses to administer medications, greater independence and the ability to maintain the same routine as home. When asked what participants would change, 16 (52%) stated nothing, 10 (32%) wanted the assessment process to allow for faster progression through the levels of SAM, 4 (13%) asked for larger medication lockers and 1 (3%) wanted better communication about new medications. 30 nursing questionnaires were completed and highlighted that nursing staff spent less time on administering medicines. Nurses also stated that medication administration was less pressurised as double-checking of doses could be performed with the participant, rather than another nurse. Their main concern was the extra documentation required for SAM. Where PODs were used for patients, the average cost saving per patient over a 3 month period was £1023. CONCLUSION: The pilot scheme has been well received by staff and patients/parents/carers, allowing greater engagement in the administration of medicines and cost-savings. As a result of this, the SAM scheme will be extended to the remaining patients on the ward.

Risk-benefit considerations when prescribing phosphodiesterase-5 inhibitors in children.

INTRODUCTION: Sildenafil (Revatio®) and tadalafil (Adcirca®) are specific inhibitors of the phosphodiesterase-5 enzyme and produce pulmonary vasodilation by inhibiting the breakdown of cyclic guanosine monophosphate (cGMP) in the walls of pulmonary arterioles. AREAS COVERED: We focus on the efficacy and safety of sildenafil and tadalafil in the treatment of pulmonary hypertension (PH) in children through a PubMed literature search. EXPERT OPINION: Although used since 1999 in the treatment of PH in children, it is only in the past few years that robust evidence for the use of sildenafil has emerged principally in the pivotal STARTS-1 study. The open-label extension of this study, STARTS-2, has revealed safety concerns substantiated by FDA post marketing surveillance leading to recommendations to use lower doses. More recently, tadalafil has been introduced allowing once daily dosing with apparently similar efficacy to sildenafil in children. Recently there have been suggestions that sildenafil and tadalafil may have a place in treating muscular dystrophy.