Immediate oral versus immediate topical versus delayed oral antibiotics for children with acute otitis media with discharge: the REST three-arm non-inferiority electronic platform-supported RCT.

BACKGROUND: Acute otitis media is a painful infection of the middle ear that is commonly seen in children. In some children, the eardrum spontaneously bursts, discharging visible pus (otorrhoea) into the outer ear. OBJECTIVE: To compare the clinical effectiveness of immediate topical antibiotics or delayed oral antibiotics with the clinical effectiveness of immediate oral antibiotics in reducing symptom duration in children presenting to primary care with acute otitis media with discharge and the economic impact of the alternative strategies. DESIGN: This was a pragmatic, three-arm, individually randomised (stratified by age < 2 vs. ≥ 2 years), non-inferiority, open-label trial, with economic and qualitative evaluations, supported by a health-record-integrated electronic trial platform [TRANSFoRm (Translational Research and Patient Safety in Europe)] with an internal pilot. SETTING: A total of 44 English general practices. PARTICIPANTS: Children aged ≥ 12 months and < 16 years whose parents (or carers) were seeking medical care for unilateral otorrhoea (ear discharge) following recent-onset (≤ 7 days) acute otitis media. INTERVENTIONS: (1) Immediate ciprofloxacin (0.3%) solution, four drops given three times daily for 7 days, or (2) delayed 'dose-by-age' amoxicillin suspension given three times daily (clarithromycin twice daily if the child was penicillin allergic) for 7 days, with structured delaying advice. All parents were given standardised information regarding symptom management (paracetamol/ibuprofen/fluids) and advice to complete the course. COMPARATOR: Immediate 'dose-by-age' oral amoxicillin given three times daily (or clarithromycin given twice daily) for 7 days. Parents received standardised symptom management advice along with advice to complete the course. MAIN OUTCOME MEASURE: Time from randomisation to the first day on which all symptoms (pain, fever, being unwell, sleep disturbance, otorrhoea and episodes of distress/crying) were rated 'no' or 'very slight' problem (without need for analgesia). METHODS: Participants were recruited from routine primary care appointments. The planned sample size was 399 children. Follow-up used parent-completed validated symptom diaries. RESULTS: Delays in software deployment and configuration led to small recruitment numbers and trial closure at the end of the internal pilot. Twenty-two children (median age 5 years; 62% boys) were randomised: five, seven and 10 to immediate oral, delayed oral and immediate topical antibiotics, respectively. All children received prescriptions as randomised. Seven (32%) children fully adhered to the treatment as allocated. Symptom duration data were available for 17 (77%) children. The median (interquartile range) number of days until symptom resolution in the immediate oral, delayed oral and immediate topical antibiotic arms was 6 (4-9), 4 (3-7) and 4 (3-6), respectively. Comparative analyses were not conducted because of small numbers. There were no serious adverse events and six reports of new or worsening symptoms. Qualitative clinician interviews showed that the trial question was important. When the platform functioned as intended, it was liked. However, staff reported malfunctioning software for long periods, resulting in missed recruitment opportunities. Troubleshooting the software placed significant burdens on staff. LIMITATIONS: The over-riding weakness was the failure to recruit enough children. CONCLUSIONS: We were unable to answer the main research question because of a failure to reach the required sample size. Our experience of running an electronic platform-supported trial in primary care has highlighted challenges from which we have drawn recommendations for the National Institute for Health Research (NIHR) and the research community. These should be considered before such a platform is used again. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12873692 and EudraCT 2017-003635-10. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 67. See the NIHR Journals Library website for further project information.

Ear infections are common in childhood. Some are complicated by a burst eardrum, followed by discharge from the ear. The usual treatment for this is a short course of antibiotics taken by mouth. However, alternative treatment using antibiotic drops, or a 'wait and see' policy before starting antibiotics, would result in less antibiotic use and reduce the subsequent risk of antibiotic resistance, which is bad for both patients and the environment. This study set out to see if these alternative treatments were as effective as the usual treatment for children with ear discharge. Although ear infections are common, only one in six children develops ear discharge, so only a few children might be available to take part at each general practice. We planned to use an electronic recruitment system to help us to gather enough patients. The system [called the 'TRANSFoRm' (Translational Research and Patient Safety in Europe) platform] was designed to remind busy general practitioners and nurses about the study and take them through the recruitment process step by step, as well as to support trial processes. Although the TRANSFoRm platform had been developed and tested, it had not been used in general practices before. We were surprised to find that there were many technical problems in setting up the TRANSFoRm platform in general practices, and staff were too busy and/or did not have the skills to overcome the technical issues. As a result, recruiting patients was slow and the study was halted before we had enough children to answer the main research question. In total, we managed to get 44 general practices and 22 children, but this was not enough. We still think that this kind of research and electronic trial platforms are important. We have noted many system and technical issues that need to be solved to enable funders and researchers to use this recruitment approach in the future.

Deaths of people with intellectual disabilities: Analysis of deaths in England from COVID-19 and other causes.

BACKGROUND: People with intellectual disabilities experience significant health inequities. The aim of this report is to understand the circumstances leading to death from COVID-19 in people with intellectual disabilities. METHOD: Local areas in England prioritised reviewing 200 deaths of adults with intellectual disabilities. Of these, approximately 80% were required to be deaths from suspected or confirmed COVID-19 as this was the focus of the study; the remainder from other causes. All deaths occurred between 2 March2020 and 9 June 2020. RESULTS: People with intellectual disabilities differed from the general population in their symptoms of COVID-19 and age at death. The overall quality of care was rated similar to other deaths of people with intellectual disabilities. Concerns were raised relating to recognising acute deterioration and do not attempt cardio-pulmonary resuscitation decisions. CONCLUSIONS: Service improvements are indicated in the ways in which people with intellectual disabilities encounter COVID-19 and experience the disease.