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Background: The COVID-19 pandemic dramatically affected asthma monitoring in primary care. Yet, patients’ views and experiences of managing their asthma and seeking help from primary care during the pandemic have not been explored. Aim: To investigate patients’ experiences of asthma management in the community during the COVID-19 pandemic. Design and setting: A qualitative longitudinal study using semi-structured interviews with asthma patients usually managed in primary care. Method: Interviews were audio recorded, transcribed and analysed using inductive temporal thematic analysis and trajectory approach. Results: Forty-six interviews were conducted with 18 asthma patients over eight months that covered contrasting stages of the pandemic. Patients felt less vulnerable as the pandemic subsided but the process of making sense of risk was dynamic and influenced by multiple factors. Patients relied on self-management strategies but felt that routine asthma reviews should still have been conducted during the COVID-19 pandemic and highlighted limited opportunities to discuss their asthma with health care professionals. Patients with well controlled symptoms felt that remote reviews were largely satisfactory but still felt that face to face reviews were necessary for certain aspects such as physical examination and patient-led discussion of sensitive or broader issues associated with asthma including mental health. Conclusions: The dynamic nature of patients’ perception of risk throughout the pandemic highlighted the need for a greater clarity regarding patients’ personal risk. Having opportunity to discuss their asthma is important to patients even during periods when access to face to face consultations in primary care is more restricted than usual.

Background: Antibiotic resistance is a global public health threat. Antibiotics are very commonly prescribed for children presenting with uncomplicated lower respiratory tract infections (LRTIs), but there is little evidence from randomised controlled trials of the effectiveness of antibiotics, both overall or among key clinical subgroups. In ARTIC PC, we assessed whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) LRTI in primary care, overall and in key clinical subgroups. Methods: ARTIC PC was a double-blind, randomised, placebo-controlled trial done at 56 general practices in England. Eligible children were those aged 6 months to 12 years presenting in primary care with acute uncomplicated LRTI judged to be infective in origin, where pneumonia was not suspected clinically, with symptoms for less than 21 days. Patients were randomly assigned in a 1:1 ratio to receive amoxicillin 50 mg/kg per day or placebo oral suspension, in three divided doses orally for 7 days. Patients and investigators were masked to treatment assignment. The primary outcome was the duration of symptoms rated moderately bad or worse (measured using a validated diary) for up to 28 days or until symptoms resolved. The primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with the ISRCTN Registry (ISRCTN79914298). Findings: Between Nov 9, 2016, and March 17, 2020, 432 children (not including six who withdrew permission for use of their data after randomisation) were randomly assigned to the antibiotics group (n=221) or the placebo group (n=211). Complete data for symptom duration were available for 317 (73%) patients; missing data were imputed for the primary analysis. Median durations of moderately bad or worse symptoms were similar between the groups (5 days [IQR 4–11] in the antibiotics group vs 6 days [4–15] in the placebo group; hazard ratio [HR] 1·13 [95% CI 0·90–1·42]). No differences were seen for the primary outcome between the treatment groups in the five prespecified clinical subgroups (patients with chest signs, fever, physician rating of unwell, sputum or chest rattle, and short of breath). Estimates from complete-case analysis and a per-protocol analysis were similar to the imputed data analysis. Interpretation: Amoxicillin for uncomplicated chest infections in children is unlikely to be clinically effective either overall or for key subgroups in whom antibiotics are commonly prescribed. Unless pneumonia is suspected, clinicians should provide safety-netting advice but not prescribe antibiotics for most children presenting with chest infections.

Objectives\udThis study aimed to assess whether the presence of bacteria or viruses in the upper airway of children presenting with uncomplicated lower respiratory tract infection (LRTI) predicts the benefit of antibiotics.\udMethods\udChildren between 6 months and 12 years presenting to UK general practices with an acute LRTI were randomized to receive amoxicillin 50 mg/kg/d for 7 days or placebo. Children not randomized (ineligible or clinician/parental choice) could participate in a parallel observational study. The primary outcome was the duration of symptoms rated moderately bad or worse. Throat swabs were taken and analyzed for the presence of bacteria and viruses by multiplex PCR.\udResults\udSwab results were available for most participants in the trial (306 of 432; 71%) and in the observational (182 of 326; 59%) studies. Bacterial pathogens potentially sensitive to amoxicillin (Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae) were detected among 51% of the trial placebo group and 49% of the trial antibiotic group. The median difference in the duration of symptoms rated moderately bad or worse between antibiotic and placebo was similar when potentially antibiotic-susceptible bacteria were present (median: –1 day; 99% CI, –12.3 to 10.3) or not present (median: –1 day; 99% CI, –4.5 to 2.5). Furthermore, bacterial genome copy number did not predict benefit. There were similar findings for all secondary outcomes and when including the data from the observational study.\udDiscussion\udThere was no clear evidence that antibiotics improved clinical outcomes conditional on the presence or concentration of bacteria or viruses in the upper airway. Before deploying microbiologic point-of-care tests for children with uncomplicated LRTI in primary care, rigorous validating trials are needed.

BackgroundGuidelines recommend measuring temperature in children presenting with fever using electronic axillary or tympanic thermometers. Non-contact thermometry offers advantages, yet has not been tested against recommended methods in primary care.AimTo compare two different non-contact infrared thermometers (NCITs) to axillary and tympanic thermometers in children aged ≤5 years visiting their GP with an acute illness.Design and settingMethod comparison study with nested qualitative component.MethodTemperature measurements were taken with electronic axillary (Welch Allyn SureTemp®), electronic tympanic (Braun Thermoscan®), NCIT Thermofocus® 0800, and NCIT Firhealth Forehead. Parents rated acceptability and discomfort. Qualitative interviews explored parents’ experiences of the thermometers.ResultsIn total, 401 children were recruited (median age 1.6 years, 50.62% male). Mean difference between the Thermofocus NCIT and axillary thermometer was −0.14°C (95% confidence interval [CI] = −0.21 to −0.06°C); lower limit of agreement was −1.57°C (95% CI = −1.69 to −1.44°C) and upper limit 1.29°C (95% CI = 1.16 to 1.42°C). A second NCIT (Firhealth) had similar levels of agreement; however, the limits of agreement between tympanic and axillary thermometers were also wide. Parents expressed a preference for the practicality and comfort of NCITs, and were mostly negative about their child’s experience of axillary thermometers. But there was willingness to adopt whichever device was medically recommended.ConclusionIn a primary care paediatric population, temperature measurements with NCITs varied by >1°C compared with axillary and tympanic approaches. But there was also poor agreement between tympanic and axillary thermometers. Since clinical guidelines often rely on specific fever thresholds, clinicians should interpret peripheral thermometer readings with caution and in the context of a holistic assessment of the child.

Background There remains public misconception about antibiotic use and resistance. Preschool children are at particular risk of receiving unnecessary antibiotics because they commonly present in primary care and many childhood infections are self-limiting. Objectives The aim of our study was to explore parents’ perceptions and understanding of antibiotic use and resistance in the context of their young child with an acute respiratory tract infection (RTI) and to explore strategies parents would find acceptable to minimize antibiotic resistance for their families. Methods Semi-structured interviews were conducted with 23 parents of preschool children who recently had an acute RTI across greater Oxfordshire, UK (2016–17 winter). We explored their beliefs about antibiotics, understanding of antibiotic resistance and views on current public antibiotic awareness campaigns at the time. Thematic analysis was used to analyse the data. Results Parents had a sense of optimism and considered their families to be at low risk of antibiotic resistance because their families were ‘low users’ of antibiotics. Very few parents considered antibiotic resistance as a possible harm of antibiotics. Parents thought they were acting morally responsibly by following campaign messages. They wanted future campaigns to have a relevant, accessible message for families about the impact of antibiotic resistance. Conclusions Future communication about the potential impact of unnecessary antibiotic use and antibiotic resistance needs to focus on outcomes that parents of young children can relate to (e.g. infection recurrence) and in a format that parents will engage with (e.g. face-to-face dissemination at playgroups and parent/child community events) to make a more informed decision about the risks and benefits of antibiotics for their child.

Background Nearly 40% of parents with children aged 6 to 17 months consult a healthcare professional when their child has a high temperature. Clinical guidelines recommend temperature measurement in these children, but little is known about parents’ experiences of and beliefs about temperature measurement. This study aimed to explore parents’ concerns and beliefs about temperature measurement in children. Methods Semi-structured qualitative interviews were conducted from May 2017 to June 2018 with 21 parents of children aged 4 months to 5.5 years, who were purposively sampled from the METRIC study (a method comparison study comparing non-contact infrared thermometers to axillary and tympanic thermometers in acutely ill children). Data analysis followed a thematic approach. Results Parents described the importance of being able to detect fever, in particular high fevers, and how this then influenced their actions. The concept of “accuracy” was valued by parents but the aspects of performance which were felt to reflect accuracy varied. Parents used numerical values of temperature in four main ways: determining precision of the thermometer on repeat measures, detecting a “bad” fever, as an indication to administer antipyretics, or monitoring response to treatment. Family and social networks, the internet, and medical professionals and resources, were all key sources of advice for parents regarding fever, and guiding thermometer choice. Conclusions Temperature measurement in children has diagnostic value but can either empower, or cause anxiety and practical challenges for parents. This represents an opportunity for both improved communication between parents and healthcare professionals, and technological development, to support parents to manage febrile illness with greater confidence in the home.

Background Current options for temperature measurement in children presenting to primary care include either electronic axillary or infrared tympanic thermometers. Non-contact infrared thermometers could reduce both the distress of the child and the risk of cross-infection. Objectives The objective of this study was to compare the use of non-contact thermometers with the use of electronic axillary and infrared tympanic thermometers in children presenting to primary care. Design Method comparison study with a nested qualitative study. Setting Primary care in Oxfordshire. Participants Children aged ≤ 5 years attending with an acute illness. Interventions Two types of non-contact infrared thermometers [i.e. Thermofocus (Tecnimed, Varese, Italy) and Firhealth (Firhealth, Shenzhen, China)] were compared with an electronic axillary thermometer and an infrared tympanic thermometer. Main outcome measures The primary outcome was agreement between the Thermofocus non-contact infrared thermometer and the axillary thermometer. Secondary outcomes included agreement between all other sets of thermometers, diagnostic accuracy for detecting fever, parental and child ratings of acceptability and discomfort, and themes arising from our qualitative interviews with parents. Results A total of 401 children (203 boys) were recruited, with a median age of 1.6 years (interquartile range 0.79–3.38 years). The readings of the Thermofocus non-contact infrared thermometer differed from those of the axillary thermometer by –0.14 °C (95% confidence interval –0.21 to –0.06 °C) on average with the lower limit of agreement being –1.57 °C (95% confidence interval –1.69 to –1.44 °C) and the upper limit being 1.29 °C (95% confidence interval 1.16 to 1.42 °C). The readings of the Firhealth non-contact infrared thermometer differed from those of the axillary thermometer by –0.16 °C (95% confidence interval –0.23 to –0.09 °C) on average, with the lower limit of agreement being –1.54 °C (95% confidence interval –1.66 to –1.41 °C) and the upper limit being 1.22 °C (95% confidence interval 1.10 to 1.34 °C). The difference between the first and second readings of the Thermofocus was –0.04 °C (95% confidence interval –0.07 to –0.01 °C); the lower limit was –0.56 °C (95% confidence interval –0.60 to –0.51 °C) and the upper limit was 0.47 °C (95% confidence interval 0.43 to 0.52 °C). The difference between the first and second readings of the Firhealth thermometer was 0.01 °C (95% confidence interval –0.02 to 0.04 °C); the lower limit was –0.60 °C (95% confidence interval –0.65 to –0.54 °C) and the upper limit was 0.61 °C (95% confidence interval 0.56 to 0.67 °C). Sensitivity and specificity for the Thermofocus non-contact infrared thermometer were 66.7% (95% confidence interval 38.4% to 88.2%) and 98.0% (95% confidence interval 96.0% to 99.2%), respectively. For the Firhealth non-contact infrared thermometer, sensitivity was 12.5% (95% confidence interval 1.6% to 38.3%) and specificity was 99.4% (95% confidence interval 98.0% to 99.9%). The majority of parents found all methods to be acceptable, although discomfort ratings were highest for the axillary thermometer. The non-contact thermometers required fewer readings than the comparator thermometers. Limitations A method comparison study does not compare new methods against a reference standard, which in this case would be central thermometry requiring the placement of a central line, which is not feasible or acceptable in primary care. Electronic axillary and infrared tympanic thermometers have been found to have moderate agreement themselves with central temperature measurements. Conclusions The 95% limits of agreement are > 1 °C for both non-contact infrared thermometers compared with electronic axillary and infrared tympanic thermometers, which could affect clinical decision-making. Sensitivity for fever was low to moderate for both non-contact thermometers. Future work Better methods for peripheral temperature measurement that agree well with central thermometry are needed. Trial registration Current Controlled Trials ISRCTN15413321. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 53. See the NIHR Journals Library website for further project information.

Antibiotic prescription is a major driver of antibiotic resistance. The majority of antibiotic prescribing occurs in community care settings, often for respiratory infections. A substantial proportion of prescriptions are issued not according to guidelines, particularly for acute respiratory infections which can be self-limiting. Prescribers in these settings need support to prescribe antibiotics more prudently. Patients and the public also need support to manage infections which are self-limiting. This presentation presents a summary of how antimicrobial stewardship (AMS) activities are being used in community settings. Firstly, types of community-level interventions are discussed, including those aimed at clinicians, patients and the public. Next, we assess interventions based on their effectiveness at reducing antibiotic prescriptions or use and their cost-effectiveness. Finally, we discuss directions for future research and consider how the research to date could influence policy.

IntroductionThe UK government stockpiles co-amoxiclav to treat bacterial complications during influenza pandemics. This pragmatic trial examines whether early co-amoxiclav use reduces reconsultation due to clinical deterioration in “at risk” children presenting with influenza-like illness (ILI) in primary or ambulatory care.Methods“At risk” children aged from 6 months to 12 years presenting within 5 days of ILI onset were randomly assigned to oral co-amoxiclav 400/57 or a placebo twice daily for 5 days (dosing based on age±weight). “At risk” groups included children with respiratory, cardiac and neurological conditions. Randomisation was stratified by region and used a non-deterministic minimisation algorithm to balance age and current seasonal influenza vaccination status. Our target sample size was 650 children which would have allowed us to detect a reduction in the proportion of children reconsulting due to clinical deterioration from 40% to 26%, with 90% power and 5% two-tailed alpha error (including allowance for 25% loss to follow-up and an inflation factor of 1.041). Participants, caregivers and investigators were blinded to treatment allocation. Intention-to-treat analysis included all randomised participants with primary outcome data on reconsultation due to clinical deterioration within 28 days. Safety analysis included all randomised participants. Trial registration: ISRCTN 70714783. EudraCT 2013-002822-21.ResultsWe recruited 271 children between February 11, 2015 and April 20, 2018. Primary outcome data were available for 265 children. Only 61 out of 265 children (23.0%) reconsulted due to clinical deterioration. No evidence of a treatment effect was observed for reconsultation due to clinical deterioration (33 out of 133 for co-amoxiclav (24.8%) and 28 out of 132 (21.2%) for placebo; adjusted risk ratio (RR) 1.16, 95% confidence interval (CI) 0.75–1.80). There was also no evidence of a difference between groups in the proportion of children for whom one or more adverse events (AEs) were reported (32 out of 136 (23.5%) for co-amoxiclav and 22 out of 135 (16.3%) for placebo; adjusted RR 1.45, 95% CI 0.90–2.34). In total, 66 AEs were reported (co-amoxiclav, n=37; placebo, n=29). Nine serious AEs were reported per group, although none were considered related to study medication.ConclusionOur trial did not find evidence that treatment with co-amoxiclav reduces risk of reconsultation due to clinical deterioration in “at risk” children who present early with ILI during influenza season. Our findings therefore do not support early co-amoxiclav use in children with seasonal ILI.

BackgroundInfluenza and influenza-like illness (ILI) place considerable burden on healthcare systems, especially during influenza epidemics and pandemics. During the 2009/10 H1N1 influenza pandemic, UK national guidelines recommended antiviral medications for patients presenting within 72 h of ILI onset. However, it is not clear whether antiviral treatment was associated with reductions in influenza-related complications.MethodsOur study population consisted of a retrospective cohort of children aged ≤17 years who presented with influenza/ILI at UK primary care practices contributing to the Clinical Practice Research Datalink during the 2009/10 pandemic. We used doubly robust inverse-probability weighted propensity scores and physician prior prescribing instrumental variable methods to estimate the causal effect of oseltamivir prescribing on influenza-related complications. Secondary outcomes were complications requiring intervention, pneumonia, pneumonia or hospitalisation, influenza-related hospitalisation and all-cause hospitalisation.ResultsWe included 16 162 children, of whom 4028 (24.9%) were prescribed oseltamivir, and 753 (4.7%) had recorded complications. Under propensity score analyses oseltamivir prescriptions were associated with reduced influenza-related complications (risk difference (RD) −0.015, 95% CI −0.022–−0.008), complications requiring further intervention, pneumonia, pneumonia or hospitalisation and influenza-related hospitalisation, but not all-cause hospitalisation. Adjusted instrumental variable analyses estimated reduced influenza-related complications (RD −0.032, 95% CI −0.051–−0.013), pneumonia or hospitalisation, all-cause and influenza-related hospitalisations.ConclusionsBased on causal inference analyses of observational data, oseltamivir treatment in children with influenza/ILI was associated with a small but statistically significant reduction in influenza-related complications during an influenza pandemic.

ObjectiveTo estimate the costs and outcomes associated with treating non-asthmatic adults (nor suffering from other lung-disease) presenting to primary care with acute lower respiratory tract infection (ALRTI) with oral corticosteroids compared with placebo.DesignCost-consequence analysis alongside a randomised controlled trial. Perspectives included the healthcare provider, patients and productivity losses associated with time off work.SettingFifty-four National Health Service (NHS) general practices in England.Participants398 adults attending NHS primary practices with ALRTI but no asthma or other chronic lung disease, followed up for 28 days.Interventions2× 20 mg oral prednisolone per day for 5 days versus matching placebo tablets.Outcome measuresQuality-adjusted life years using the 5-level EuroQol-5D version measured weekly; duration and severity of symptom. Direct and indirect resources related to the disease and its treatment were also collected. Outcomes were measured for the 28-day follow-up.Results198 (50%) patients received the intervention (prednisolone) and 200 (50%) received placebo. NHS costs were dominated by primary care contacts, higher with placebo than with prednisolone (£13.11 vs £10.38) but without evidence of a difference (95% CI £3.05 to £8.52). The trial medication cost of £1.96 per patient would have been recouped in prescription charges of £4.30 per patient overall (55% participants would have paid £7.85), giving an overall mean ‘profit’ to the NHS of £7.00 (95% CI £0.50 to £17.08) per patient. There was a quality adjusted life years gain of 0.03 (95% CI 0.01 to 0.05) equating to half a day of perfect health favouring the prednisolone patients; there was no difference in duration of cough or severity of symptoms.ConclusionsThe use of prednisolone for non-asthmatic adults with ALRTI, provided small gains in quality of life and cost savings driven by prescription charges. Considering the results of the economic evaluation and possible side effects of corticosteroids, the short-term benefits may not outweigh the long-term harms.Trial registration numbersEudraCT 2012-000851-15 and ISRCTN57309858; Pre-results.

Background: Around 16 million cases of whooping cough (pertussis) occur worldwide each year, mostly in low‐income countries. Much of the morbidity of whooping cough in children and adults is due to the effects of the paroxysmal cough. Cough treatments proposed include corticosteroids, beta2‐adrenergic agonists, pertussis‐specific immunoglobulin, antihistamines and possibly leukotriene receptor antagonists (LTRAs). Objectives: To assess the effectiveness and safety of interventions to reduce the severity of paroxysmal cough in whooping cough in children and adults. Search methods: We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, the Database of Abstracts of Reviews of Effects (DARE 2014, Issue 2), accessed from The Cochrane Library, MEDLINE (1950 to 30 January 2014), EMBASE (1980 to 30 January 2014), AMED (1985 to 30 January 2014), CINAHL (1980 to 30 January 2014) and LILACS (30 January 2014). We searched Current Controlled Trials to identify trials in progress. Selection criteria: We selected randomised controlled trials (RCTs) and quasi‐RCTs of any intervention (excluding antibiotics and vaccines) to suppress the cough in whooping cough. Data collection and analysis: Two review authors (SB, MT) independently selected trials, extracted data and assessed the quality of each trial for this review in 2009. Two review authors (SB, KW) independently reviewed additional studies identified by the updated searches in 2012 and 2014. The primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis (turning blue), development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay. Main results: We included 12 trials of varying sample sizes (N = 9 to 135), mainly from high‐income countries, including a total of 578 participants. Ten trials recruited children (N = 448 participants). Two trials recruited adolescents and adults (N = 130 participants). We considered only three trials to be of high methodological quality (one trial each of diphenhydramine, pertussis immunoglobulin and montelukast). Included studies did not show a statistically significant benefit for any of the interventions. Only six trials, including a total of 196 participants, reported data in sufficient detail for analysis. Diphenhydramine did not change coughing episodes; the mean difference (MD) of coughing spells per 24 hours was 1.9; 95% confidence interval (CI) ‐4.7 to 8.5 (N = 49 participants from one trial). One trial on pertussis immunoglobulin reported a possible mean reduction of ‐3.1 whoops per 24 hours (95% CI ‐6.2 to 0.02, N = 47 participants) but no change in hospital stay (MD ‐0.7 days; 95% CI ‐3.8 to 2.4, N = 46 participants). Dexamethasone did not show a clear decrease in length of hospital stay (MD ‐3.5 days; 95% CI ‐15.3 to 8.4, N = 11 participants from one trial) and salbutamol showed no change in coughing paroxysms per day (MD ‐0.2; 95% CI ‐4.1 to 3.7, N = 42 participants from two trials). Only one trial comparing pertussis immunoglobulin versus placebo (N = 47 participants) reported data on adverse events: 4.3% in the treatment group (rash) versus 5.3% in the placebo group (loose stools, pain and swelling at injection site). Authors' conclusions: There is insufficient evidence to draw conclusions about the effectiveness of interventions for the cough in whooping cough. More high‐quality trials are needed to assess the effectiveness of potential antitussive treatments in patients with whooping cough

Background Acute lower respiratory tract infection (LRTI) is one of the most common conditions managed internationally and is costly to health services and patients. Despite good evidence that antibiotics are not effective for improving the symptoms of uncomplicated LRTI, they are widely prescribed, contributing to antimicrobial resistance. Many of the symptoms observed in LRTI are mediated by inflammatory processes also observed in exacerbations of asthma, for which there is strong evidence of corticosteroid effectiveness. The primary aim of the OSAC (Oral Steroids for Acute Cough) Trial is to determine whether oral prednisolone (40 mg daily for 5 days) can reduce the duration of moderately bad (or worse) cough and the severity of all its associated symptoms on days 2 to 4 post-randomisation (day 1 is trial entry) by at least 20% in adults ≥18 years with acute LRTI presenting to primary care. Methods/design OSAC is a two-arm, multi-centre, placebo-controlled, randomised superiority trial. The target sample size is 436 patients, which allows for a 20% dropout rate. Patients will be recruited from primary care sites (General Practitioner surgeries) across England and followed up until symptom resolution. The two primary clinical outcomes are the duration of moderately bad (or worse) cough, and the severity of all its associated symptoms on days 2 to 4 post-randomisation. Secondary outcomes include: antibiotic consumption; symptom burden; adverse events; participant satisfaction with treatment and intention to consult for future similar illnesses. A parallel economic evaluation will investigate the cost-effectiveness of the intervention. Discussion Results from the OSAC trial will increase knowledge regarding the clinical and cost-effectiveness of corticosteroids for LRTI, and will establish the potential of a new treatment option that could substantially improve patient health. We have chosen a relatively high ‘efficacy dose’ as this will enable us to decide on the potential for further research into lower dose oral and/or inhaled corticosteroids. This trial will also contribute to a growing body of research investigating the natural course of this very common illness, as well as the effects of steroids on the undesirable inflammatory symptoms associated with infection. Trial registration Current Controlled Trials ISRCTN57309858 (31 January 2013). Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-0569-5) contains supplementary material, which is available to authorized users.

BackgroundChildhood antibiotic exposure has important clinically relevant implications. These include disruption to the microbiome, antibiotic resistance, and clinical workload manifesting as treatment ‘failure’.AimTo examine the relationship between the number of antibiotic courses prescribed to preschool children for acute respiratory tract infections (RTI), in the preceding year, and subsequent RTIs that failed to respond to antibiotic treatment (‘response failures’).Design and settingA cohort study using UK primary care data from the Clinical Practice Research Datalink, 2009 to 2016.MethodChildren aged 12 to 60 months (1 to 5 years) who were prescribed an antibiotic for an acute RTI (upper and lower RTI or otitis media) were included. One random index antibiotic course for RTI per child was selected. Exposure was the number of antibiotic prescriptions for acute RTI up to 12 months before the index antibiotic prescription. The outcome was ‘response failure’ up to 14 days after index antibiotic prescription, defined as: subsequent antibiotic prescription; referral; hospital admission; death; or emergency department attendance within 3 days. The authors used logistic regression models to estimate the odds between antibiotic exposure and response failure.ResultsOut of 114 329 children who were prescribed an antibiotic course for acute RTI, children who received ≥2 antibiotic courses for acute RTIs in the preceding year had greater odds of response failure; one antibiotic course: adjusted odds ratio (OR) 1.03 (95% confidence interval [CI] = 0.88 to 1.21), P = 0.67, n = 230 children; ≥2 antibiotic courses: adjusted OR 1.32 (CI = 1.04 to 1.66), P = 0.02, n = 97.ConclusionChildhood antibiotic exposure for acute RTI may be a good predictor for subsequent response failure (but not necessarily because of antibiotic treatment failure). Further research is needed to improve understanding of the mechanisms underlying response failure.

Introduction: Fractional exhaled nitric oxide (FeNO) is a marker of steroid-responsive airway inflammation, but it is still unclear how FeNO should be used to identify patients with steroid-responsive respiratory symptoms. Aims and Objectives: To assess the prognostic value of using FeNO to identify patients with respiratory symptoms who are likely to respond symptomatically to inhaled corticosteroids (ICS). Methods: We performed a systematic electronic database search to identify studies which recruited patients aged >=12 years with suspected asthma or non-specific respiratory symptoms. We defined symptomatic response to ICS as Asthma Control Questionnaire (ACQ) score improvement of >=0.5. We performed multi-level mixed-effects logistic regression accounting for within-study clustering, FeNO, age, sex, smoking, atopy and baseline ACQ score. We also estimated sensitivities and specificities for a range of FeNO values and predicted probabilities of ICS response. Results: We analysed individual patient data from six studies (517 patients). A FeNO cut-off of 40 ppb predicted ICS response with sensitivity 0.38 (95% confidence interval [CI] 0.18-0.63) and specificity 0.74 (95% CI 0.52-0.89). A 20 ppb cut-off gave sensitivity 0.70 (95% CI 0.50-0.85) and specificity 0.40 (95% CI 0.27-0.55). A 60% predicted probability of ICS response based on our regression model had greatest prognostic accuracy (sensitivity 0.78, 95% CI 0.55-0.91; specificity 0.73, 95% CI 0.52-0.87). Conclusions: FeNO has greatest utility in predicting ICS response when considered with other prognostic factors. A predicted probability of >=60% is most accurate in identifying patients likely to respond symptomatically to ICS.

Introduction: Use of fractional exhaled nitric oxide (FeNO) is recommended for asthma diagnosis but its role in guiding safe reduction of inhaled corticosteroids (ICS) is unclear. Aims and objectives: To assess the value of FeNO in identifying asthma patients in whom ICS can be safely reduced. Methods: We performed a systematic electronic database search to identify studies which recruited asthma patients aged >=12 years maintained on low to moderate dose ICS in whom FeNO was measured at baseline before subsequently stepping down ICS treatment, irrespective of what the baseline FeNO value was. We performed multi-level mixed-effects logistic regression in relation to absence or presence of acute exacerbations up to 12 weeks after stepping down ICS, accounting for within-study clustering, age, sex and FeNO. FeNO was categorised as low (20 ppb to =50 ppb). Results: We obtained individual patient data from seven studies (393 patients; acute exacerbation, n=44). After adjustment for all baseline covariates in our regression model, exacerbation risk was significantly lower in patients with low FeNO (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.16-0.86, P=0.021) or intermediate FeNO (OR 0.23, 95% CI 0.09-0.59, P=0.002) than in patients with high FeNO at baseline. Conclusion: Patients with mild-to-moderate asthma whose FeNO is >=50 ppb are at greater risk of exacerbation following ICS reduction than patients whose FeNO is in the low or intermediate range. Assessment of FeNO is therefore important in guiding safe clinical decisions about stepping down treatment in asthma patients who appear to be symptomatically controlled on low or moderate dose ICS.

Using FENO to guide safe step-down treatment decisions in patients with well-controlled asthma should involve gradual, carefully monitored reductions and consider other potential risk factors for acute exacerbationshttps://bit.ly/2E2W679

Getting a true measure of disease prevalence is difficult but fundamental to medicine. The process itself is valuable, but the results have to be reviewed in the context of the healthcare system and country they were collected in.https://bit.ly/2ThxaxF

BackgroundHigh exhaled nitric oxide fraction (FENO) levels are associated with greater risk of asthma exacerbation. However, it is not clear how FENO can be used to guide safe reductions in inhaled corticosteroid (ICS) doses in asthma patients. This study assesses the ability of FENO to guide ICS reductions.MethodsSystematic searching of electronic databases identified prospective observational studies and randomised controlled trials which recruited participants with mild-to-moderate asthma aged ≥12 years and measured FENO before reducing ICS. We performed multilevel mixed-effects logistic regression in relation to acute exacerbations and estimated each participant's exacerbation risk using our logistic regression model.ResultsWe included data from seven out of eight eligible studies, representing 384 participants. ICS doses were halved in four studies and withdrawn in three studies. A baseline FENO measurement of ≥50 ppb was associated with increased risk of exacerbations (crude OR 3.14, 95% CI 1.41–7.00, p=0.005; adjusted OR 3.08, 95% CI 1.36–6.98, p=0.007) and corresponded to an estimated exacerbation risk cut-off of 15%. Reducing ICS when estimated exacerbation risk was versus versus 141 (36.7%) out of 384), but similar proportions of patients avoiding exacerbations (222 (91.4%) out of 243, 95% CI 87.1–94.6% versus 311 (90.4%) out of 344, 95% CI 86.8–93.3%).ConclusionIn patients with mild-to-moderate asthma, gradual ICS reduction when FENO is

IntroductionInfluenza and influenza-like illness (ILI) create considerable burden on healthcare resources each winter. Children with pre-existing conditions such as asthma, diabetes mellitus and cerebral palsy are among those at greatest risk of clinical deterioration from influenza/ILI. The Antibiotics for at Risk CHildren with InfluEnza (ARCHIE) trial aims to determine whether early oral treatment with the antibiotic co-amoxiclav reduces the likelihood of reconsultation due to clinical deterioration in these ‘at risk’ children.Methods and analysisThe ARCHIE trial is a double-blind, parallel, randomised, placebo-controlled trial. ‘At risk’ children aged 6 months to 12 years inclusive who present within the first 5 days of an ILI episode will be randomised to receive a 5-day course of oral co-amoxiclav 400/57 twice daily or placebo. Randomisation will use a non-deterministic minimisation algorithm to balance age and seasonal influenza vaccination status.To detect respiratory virus infections, a nasal swab will be obtained from each participant before commencing study medication. To identify carriage of potential bacterial respiratory pathogens, we will also obtain a throat swab where possible.The primary outcome is reconsultation in any healthcare setting due to clinical deterioration within 28 days of randomisation. We will analyse this outcome using log-binomial regression model adjusted for region, age and seasonal influenza vaccination status.Secondary outcomes include duration of fever, duration of symptoms and adverse events. Continuous outcomes will be compared using regression analysis (or equivalent non-parametric method for non-normal data) adjusting for minimisation variables. Binary outcomes will be compared using χ2/Fisher’s exact test and log-binomial regression.EthicsThe ARCHIE trial has been reviewed and approved by the North West-Liverpool East Research Ethics Committee, Health Research Authority and Medicines and Healthcare Products Regulatory Agency. Our findings will be published in peer-reviewed journals and disseminated via our study website (www.archiestudy.com) and links with relevant charities.Trial registration numbersISRCTN70714783; Pre-results.

Primary care clinicians have a central role in managing influenza/influenza-like illness (ILI) during influenza pandemics. This study identifies risk factors for influenza-related complications in children presenting with influenza/ILI in primary care. We conducted a cohort study using routinely collected linked data from the Clinical Practice Research Datalink on children aged 17 years and younger who presented with influenza/ILI during the 2009/10 pandemic. We calculated odds ratios (ORs) for potential risk factors in relation to influenza-related complications, complications requiring intervention, pneumonia, all-cause hospitalisation and hospitalisation due to influenza-related complications within 30 days of presentation. Analyses were adjusted for potential confounders including age, vaccination and socio-economic deprivation. Asthma was a risk factor for influenza-related complications (adjusted OR 1.48, 95% confidence interval (CI) 1.21–1.80, P < 0.001), complications requiring intervention (adjusted OR 1.44, 95% CI 1.11–1.88; P = 0.007), pneumonia (adjusted OR 1.64, 95% CI 1.07–2.51, P = 0.024) and hospitalisation due to influenza-related complications (adjusted OR 2.46, 95% CI 1.09–5.56, P = 0.031). Neurological conditions were risk factors for all-cause hospitalisation (adjusted OR 4.25, 95% CI 1.50–12.07, P = 0.007) but not influenza-related complications (adjusted OR 1.46, 95% CI 0.83–2.56, P = 0.189). Community-based early interventions to prevent influenza-related clinical deterioration should therefore be primarily targeted at children with asthma and neurological conditions.

Background No current guidance is available in the UK on the choice of preference-based measure (PBM) that should be used in obtaining health-related quality of life from children. The aim of this study is to review the current usage of PBMs for obtaining health state utility values in child and adolescent populations, and to obtain information on patient and parent–proxy respondent preferences in completing PBMs in the UK. Methods A literature review was conducted to determine which instrument is most frequently used for child-based economic evaluations and whether child or proxy responses are used. Instruments were compared on dimensions, severity levels, elicitation and valuation methods, availability of value sets and validation studies, and the range of utility values generated. Additionally, a series of focus groups of parents and young people (11–20 years) were convened to determine patient and proxy preferences. Results Five PBMs suitable for child populations were identified, although only the Health Utilities Index 2 (HUI2) and Child Heath Utility 9D (CHU-9D) have UK value sets. 45 papers used PBMs in this population, but many used non-child-specific PBMs. Most respondents were parent proxies, even in adolescent populations. Reported missing data ranged from 0.5 to 49.3%. The focus groups reported their experiences with the EQ-5D-Y and CHU-9D. Both the young persons’ group and parent/proxy groups felt that the CHU-9D was more comprehensive but may be harder for a proxy to complete. Some younger children had difficulty understanding the CHU-9D questions, but the young persons’ group nonetheless preferred responding directly. Conclusion The use of PBMs in child populations is increasing, but many studies use PBMs that do not have appropriate value sets. Parent proxies are the most common respondents, but the focus group responses suggest it would be preferred, and may be more informative, for older children to self-report or for child–parent dyads to respond. Electronic supplementary material The online version of this article (10.1007/s11136-018-1831-6) contains supplementary material, which is available to authorized users.

Influenza is a major global cause of childhood morbidity and mortality, and puts a strain on healthcare resources, particularly during epidemics and pandemics. Annual seasonal influenza vaccination programmes were launched to help reduce the burden of influenza but there is variation between countries on which children are targeted. Certain national programmes (for example, in Canada and the USA) recommend universal influenza vaccination while most European countries still focus mainly on groups considered to be at greater risk of influenza-related complications. These include children with certain known underlying medical conditions and those under 2 years of age. In this issue of the European Respiratory Journal, HARDELID et al. provide evidence to inform influenza vaccine strategies by identifying risk factors for influenza-related hospital admission in children younger than 2 years of age. The cohort study of 402 762 singleton livebirths in Scotland from 2007 to 2015 used data linkages between birth and death registration, hospital administrative data and influenza laboratory reports from 2009 to 2015 (six influenza seasons). They identified 1019 influenza-confirmed hospital admissions during the study period, or 2.57 per 1000 child-years in children aged less than 6 months and 2.07 per 1000 child years in children aged 6–23 months. The study findings highlight several limitations of current influenza immunisation programmes.

Background: Interventions to prevent influenza-related complications are recommended for individuals at the greatest risk of serious clinical deterioration. However, guidelines are based on consensus opinion rather than evidence, and do not specify risk factors in children. We aimed to provide an evidence-based definition of children who are most at risk of such complications. Methods: In this systematic review, we searched the Medline and Medline In Process, Embase, Science Citation Index, and CINAHL databases for studies published between inception and April 3, 2013. We included studies that reported data for underlying disorders and complications in children presenting in primary or ambulatory care with influenza or influenza-like illness. We requested unpublished data from investigators of studies that had obtained, but not published, relevant data. We analysed data with univariable meta-analysis and individual patient data multivariable meta-analysis methods. The primary outcome was admission to hospital as a proxy for complications of influenza or influenza-like illness. Findings: We included 28 articles that reported data from 27 studies (14 086 children). Strong risk factors for hospital admission were neurological disorders (univariable odds ratio [OR] 4· 62, 95% CI 2·82–7·55), prematurity (4·33, 2·47–7·58), sickle cell disease (3·46, 1·63–7·37), immunosuppression (2·39, 1·24–4·61), diabetes (2·34, 1·20–4·58), and age younger than 2 years (2·51, 1·71–3·69). However, reactive airways disease including asthma (1·36, 0·82–2·26) and obesity (0·99, 0·61–1·62) were not found to be risk factors. On the basis of individual patient data multivariable analysis (1612 children, four studies), the risk of hospital admission was higher in children with more than one risk factor than in children with just one risk factor, when age younger than 2 years was included as a risk factor (92 [74%] of 124 vs 428 [52%] of 817; difference 22%, 95% CI 13–30%, p Interpretation: We identified prematurity as a new strong risk factor for influenza-related complications in children. Our findings also support the inclusion of neurological disorders, sickle cell disease, immunosuppression, diabetes, and age younger than 2 years as risk factors in existing guidelines. Interventions to prevent influenza-related complications should be prioritised in these groups, but should also be considered for other children, especially those with more than one risk factor or severe underlying comorbidities. Funding: UK National Institute for Health Research.

Background Worldwide, pertussis remains a major health problem among children. During the recent outbreaks of pertussis, maternal antenatal immunisation was introduced in several industrial countries. This systematic review aimed to synthesize evidence for the efficacy and safety of the pertussis vaccination that was given to pregnant women to protect infants from pertussis infection. Methods We searched literature in the Cochrane Central Register of Controlled Trials, Medline, Embase, and OpenGrey between inception of the various databases and 16 May 2016. The search terms included ‘pertussis’, ‘whooping cough’, ‘pertussis vaccine,’ ‘tetanus, diphtheria and pertussis vaccines’ and ‘pregnancy’ and ‘perinatal’. Results We included 15 articles in this review, which represented 12 study populations, involving a total of 203,835 mother-infant pairs from the US, the UK, Belgium, Israel, and Vietnam. Of the included studies, there were two randomised controlled trials (RCTs) and the rest were observational studies. Existing evidence suggests that vaccinations administered during 19–37 weeks of gestation are associated with significantly increased antibody levels in the blood of both mothers and their newborns at birth compared to placebo or no vaccination. However, there is a lack of robust evidence to suggest whether these increased antibodies can also reduce the incidence of pertussis (one RCT, n = 48, no incidence in either group) and pertussis-related severe complications (one observational study) or mortality (no study) in infants. Meanwhile, there is no evidence of increased risk of serious complications such as stillbirth (e.g. one RCT, n = 103, RR = 0, meaning no case in the vaccine group), or preterm birth (two RCTs, n = 151, RR = 0.86, 95%CI: 0.14–5.21) related to administration of the vaccine during pregnancy. Conclusion Given that pertussis infection is increasing in many countries and that newborn babies are at greatest risk of developing severe complications from pertussis, maternal vaccination in the later stages of pregnancy should continue to be supported while further research should fill knowledge gaps and strengthen evidence of its efficacy and safety. Electronic supplementary material The online version of this article (10.1186/s12884-017-1559-2) contains supplementary material, which is available to authorized users.

An annual review is recommended for children with asthma but objective measures of control are lacking.1 Monitoring exacerbations and a symptom score are both suggested, but the widely used Children’s Asthma Control Test (C-ACT) has a positive predictive value of only 46.7% for asthma exacerbations at the recommended score of

Background: Antibiotic resistance is a worldwide health threat. Interventions that reduce antibiotic prescribing by clinicians are expected to reduce antibiotic resistance. Disparate interventions to change antibiotic prescribing behaviour for acute respiratory infections (ARIs) have been trialled and meta-analysed, but not yet synthesised in an overview. This overview synthesises evidence from systematic reviews, rather than individual trials. Objectives: To systematically review the existing evidence from systematic reviews on the effects of interventions aimed at influencing clinician antibiotic prescribing behaviour for ARIs in primary care. Methods: We searched the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), MEDLINE, Embase, CINAHL, PsycINFO, and Science Citation Index to June 2016. We also searched the reference lists of all included reviews. We ran a pre-publication search in May 2017 and placed additional studies in 'awaiting classification'. We included both Cochrane and non-Cochrane reviews of randomised controlled trials evaluating the effect of any clinician-focussed intervention on antibiotic prescribing behaviour in primary care. Two overview authors independently extracted data and assessed the methodological quality of included reviews using the ROBIS tool, with disagreements reached by consensus or by discussion with a third overview author. We used the GRADE system to assess the quality of evidence in included reviews. The results are presented as a narrative overview. Main results: We included eight reviews in this overview: five Cochrane Reviews (33 included trials) and three non-Cochrane reviews (11 included trials). Three reviews (all Cochrane Reviews) scored low risk across all the ROBIS domains in Phase 2 and low risk of bias overall. The remaining five reviews scored high risk on Domain 4 of Phase 2 because the 'Risk of bias' assessment had not been specifically considered and discussed in the review Results and Conclusions. The trials included in the reviews varied in both size and risk of bias. Interventions were compared to usual care. Moderate-quality evidence indicated that C-reactive protein (CRP) point-of-care testing (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.66 to 0.92, 3284 participants, 6 trials), shared decision making (odds ratio (OR) 0.44, 95% CI 0.26 to 0.75, 3274 participants, 3 trials; RR 0.64, 95% CI 0.49 to 0.84, 4623 participants, 2 trials; risk difference -18.44, 95% CI -27.24 to -9.65, 481,807 participants, 4 trials), and procalcitonin-guided management (adjusted OR 0.10, 95% CI 0.07 to 0.14, 1008 participants, 2 trials) probably reduce antibiotic prescribing in general practice. We found moderate-quality evidence that procalcitonin-guided management probably reduces antibiotic prescribing in emergency departments (adjusted OR 0.34, 95% CI 0.28 to 0.43, 2605 participants, 7 trials). The overall effect of these interventions was small (few achieving greater than 50% reduction in antibiotic prescribing, most about a quarter or less), but likely to be clinically important. Compared to usual care, shared decision making probably makes little or no difference to reconsultation for the same illness (RR 0.87, 95% CI 0.74 to 1.03, 1860 participants, 4 trials, moderate-quality evidence), and may make little or no difference to patient satisfaction (RR 0.86, 95% CI 0.57 to 1.30, 1110 participants, 2 trials, low-quality evidence). Similarly, CRP testing probably has little or no effect on patient satisfaction (RR 0.79, 95% CI 0.57 to 1.08, 689 participants, 2 trials, moderate-quality evidence) or reconsultation (RR 1.08, 95% CI 0.93 to 1.27, 5132 participants, 4 trials, moderate-quality evidence). Procalcitonin-guided management probably results in little or no difference in treatment failure in general practice compared to normal care (adjusted OR 0.95, 95% CI 0.73 to 1.24, 1008 participants, 2 trials, moderate-quality evidence), however it probably reduces treatment failure in the emergency department compared to usual care (adjusted OR 0.76, 95% CI 0.61 to 0.95, 2605 participants, 7 trials, moderate-quality evidence). The quality of evidence for interventions focused on clinician educational materials and decision support in reducing antibiotic prescribing in general practice was either low or very low (no pooled result reported) and trial results were highly heterogeneous, therefore we were unable draw conclusions about the effects of these interventions. The use of rapid viral diagnostics in emergency departments may have little or no effect on antibiotic prescribing (RR 0.86, 95% CI 0.61 to 1.22, 891 participants, 3 trials, low-quality evidence) and may result in little to no difference in reconsultation (RR 0.86, 95% CI 0.59 to 1.25, 200 participants, 1 trial, low-quality evidence). None of the trials in the included reviews reported on management costs for the treatment of an ARI or any associated complications. Authors' conclusions: We found evidence that CRP testing, shared decision making, and procalcitonin-guided management reduce antibiotic prescribing for patients with ARIs in primary care. These interventions may therefore reduce overall antibiotic consumption and consequently antibiotic resistance. There do not appear to be negative effects of these interventions on the outcomes of patient satisfaction and reconsultation, although there was limited measurement of these outcomes in the trials. This should be rectified in future trials. We could gather no information about the costs of management, and this along with the paucity of measurements meant that it was difficult to weigh the benefits and costs of implementing these interventions in practice. Most of this research was undertaken in high-income countries, and it may not generalise to other settings. The quality of evidence for the interventions of educational materials and tools for patients and clinicians was either low or very low, which prevented us from drawing any conclusions. High-quality trials are needed to further investigate these interventions.

ImportanceAcute lower respiratory tract infection is common and often treated inappropriately in primary care with antibiotics. Corticosteroids are increasingly used but without sufficient evidence. ObjectiveTo assess the effects of oral corticosteroids for acute lower respiratory tract infection in adults without asthma. Design, Setting, and ParticipantsMulticenter, placebo-controlled, randomized trial (July 2013 to final follow-up October 2014) conducted in 54 family practices in England among 401 adults with acute cough and at least 1 lower respiratory tract symptom not requiring immediate antibiotic treatment and with no history of chronic pulmonary disease or use of asthma medication in the past 5 years. InterventionsTwo 20-mg prednisolone tablets (n = 199) or matched placebo (n = 202) once daily for 5 days. Main Outcomes and MeasuresThe primary outcomes were duration of moderately bad or worse cough (0 to 28 days; minimal clinically important difference, 3.79 days) and mean severity of symptoms on days 2 to 4 (scored from 0 [not affected] to 6 [as bad as it could be]; minimal clinically important difference, 1.66 units). Secondary outcomes were duration and severity of acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, and adverse events. ResultsAmong 401 randomized patients, 2 withdrew immediately after randomization, and 1 duplicate patient was identified. Among the 398 patients with baseline data (mean age, 47 [SD, 16.0] years; 63% women; 17% smokers; 77% phlegm; 70% shortness of breath; 47% wheezing; 46% chest pain; 42% abnormal peak flow), 334 (84%) provided cough duration and 369 (93%) symptom severity data. Median cough duration was 5 days (interquartile range [IQR], 3-8 days) in the prednisolone group and 5 days (IQR, 3-10 days) in the placebo group (adjusted hazard ratio, 1.11; 95% CI, 0.89-1.39;P = .36 at an α = .05). Mean symptom severity was 1.99 points in the prednisolone group and 2.16 points in the placebo group (adjusted difference, −0.20; 95% CI, −0.40 to 0.00;P = .05 at an α = .001). No significant treatment effects were observed for duration or severity of other acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, or nonserious adverse events. There were no serious adverse events. Conclusions and RelevanceOral corticosteroids should not be used for acute lower respiratory tract infection symptoms in adults without asthma because they do not reduce symptom duration or severity. Trial RegistrationISRCTN.com Identifier:ISRCTN57309858

Background Antibiotic use is the main driver for carriage of antibiotic-resistant bacteria. The perception exists that failure of antibiotic treatment due to antibiotic resistance has little clinical impact in the community. Methods We searched MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Trials and Web of Science from inception to 15 April 2016 without language restriction. We included studies conducted in community settings which reported patient-level data on laboratory-confirmed infections (respiratory, urinary tract, skin or soft tissue), antibiotic resistance, and clinical outcomes. Our primary outcome was clinical response failure. Secondary outcomes were re-consultation, further antibiotic prescriptions, symptom duration and symptom severity. Where possible, we calculated odds ratios with 95% confidence intervals by performing meta-analysis using random effects models. Results We included 26 studies (5,659 participants).Clinical response failure was significantly more likely in participants with antibiotic-resistant Escherichia coli urinary tract infections (odds ratio [OR] 4·19,95% confidence interval [CI] 3·27–5·37,2,432 participants),Streptococcus pneumoniae otitis media (OR 2·51,95% CI 1·29–4·88,921 participants),and Streptococcus pneumoniae community-acquired pneumonia (OR 2·15,95% CI 1·32–3·51,916 participants).Clinical heterogeneity precluded primary outcome meta-analysis for Staphylococcus aureus skin or soft tissue infections. Conclusions Antibiotic resistance significantly impacts on patients’ illness burden in the community. Patients with laboratory-confirmed antibiotic-resistant urinary and respiratory tract infections are more likely to experience delays in clinical recovery after treatment with antibiotics. A better grasp of the risk of antibiotic resistance on outcomes which matter to patients should inform more meaningful discussions between health care professionals and patients about antibiotic treatment for common infections.

This review reflects upon the management of cough in primary, secondary and tertiary care settings. It reviews the burden of cough, the diagnostic tools employed to investigate the cause of cough and pragmatic treatment strategies. A clinical case vignette presenting in primary care highlights the challenges of managing cough by family practitioners. An approach to establishing a persistent cough clinic service in secondary care is described. Finally, the entity of idiopathic cough in tertiary care and the specialist approaches to treating recalcitrant cough are addressed.

This is the protocol for a review and there is no abstract. The objectives are as follows: To systematically review the literature and appraise the existing evidence from systematic reviews regarding the effects of interventions, aimed at changing clinician behaviour, to reduce antibiotic prescribing for ARIs in primary care.

Background: Persistent cough following an acute respiratory tract infection is common in children, but clinicians may find it difficult to give accurate prognostic information on likely duration of cough without a microbiologic diagnosis. This study estimates the prevalence of Mycoplasma pneumoniae (Mp) and assesses the prognostic value of detecting Mp and respiratory viruses in children with persistent cough. Methods: We retrospectively analyzed blood samples, nasopharyngeal aspirates (NPAs), and cough duration data from 179 children with persistent cough lasting 14 days or longer. Of these children, 37% had serologically confirmed Bordetella pertussis (pertussis). We detected Mp by polymerase chain reaction of NPAs and IgM serology, and respiratory viruses (human rhinoviruses, influenza viruses, respiratory syncytial viruses, and human metapneumovirus) by polymerase chain reaction of NPAs. We used Kaplan-Meier analyses to calculate median cough durations with 95% confidence intervals (CIs). Results: We detected Mp in 22 of 170 children with sufficient blood and/or NPAs (12.9%, 95% CI: 8.7-18.8). Cough duration in children with positive Mp serology (median: 39 days, 95% CI: 24-54) was significantly shorter than in children with positive pertussis serology (median: 118 days, 95% CI: 82-154, P < 0.001). The presence of respiratory viruses did not significantly lengthen cough duration in children with pertussis (median: 154 days, 95% CI: 74-234, P = 0.810). Only 3 children had both Mp and respiratory virus infections. Conclusions: Mp is an important infection in children with persistent cough and is associated with a significantly shorter duration of cough than pertussis. However, detecting respiratory viruses does not add prognostic value in children with pertussis. © 2011 by Lippincott Williams & Wilkins.

The UGT1A1 Taqman MGB probe single nucleotide polymorphism (SNP) genotyping assay was developed to detect nucleotide 211 of the UDP‐glucoronocyltransferase 1A1 (UGT1A1) gene. Defects in this enzyme interfere with process of conjugation of bilirubin and cause unconjugated hyperbilirubinemia. Variation at nucleotide 211 in the coding region of the UGT1A1 gene has been shown to be prevalent in Japanese and Chinese. Using an ABI sequence detection system (SDS) 7000, an allele‐specific real‐time PCR‐based genotyping method was established to detect nucleotide G211A. Cord blood from 125 infants without hyperbilirubinemia (controls) were compared with cord blood from 74 infants (cases) with severe hyperbilirubinemia (total serum bilirubin >300µmol/L). Homozygous variation of the UGT1A1 gene at nucleotide 211(A/A) is significantly more common in cases (14.9%) than in controls (0.8%) (P

Temperature is an important vital sign for assessing acutely unwell children, and is measured frequently in primary care. However, measuring temperature accurately can be challenging. Oral and rectal thermometers are invasive and poorly tolerated, while axillary thermometers require parents or healthcare professionals to undress the child and hold the thermometer in the axilla for 30 seconds or longer. Infrared tympanic thermometers are easier to use, but can be inaccurate due to ear wax or insufficient straightening of the ear canal. Non-contact infrared thermometers (NCITs) are designed to measure temperature rapidly and non-invasively with negligible cross-infection risk. This update compares the accuracy and utility of NCITs with conventional thermometers in children. #### Clinical Question What is the accuracy and utility of non-contact infrared thermometers compared to conventional thermometers in children? Table 1 summarises characteristics of a range of NCITs. Based on a search conducted in December 2013, over 20 models are available for use in community and/or healthcare settings. The Thermofocus and Syner-Med VeraTemp thermometers are FDA approved and CE marked. This report found six studies comparing three NCIT devices (Standard ST 88121, Thermofocus 08002,3 and Thermofocus 015004–6) to conventional thermometers in children. View this table: Table 1. Characteristics of non-contact infrared thermometers NCITs may be used to measure temperature in children presenting with acute illness in primary …

Objective To estimate the prevalence and clinical severity of whooping cough (pertussis) in school age children presenting with persistent cough in primary care since the introduction and implementation of the preschool pertussis booster vaccination. Design Prospective cohort study (November 2010 to December 2012). Setting General practices in Thames Valley, UK. Participants 279 children aged 5 to 15 years who presented in primary care with a persistent cough of two to eight weeks’ duration. Exclusion criteria were cough likely to be caused by a serious underlying medical condition, known immunodeficiency or immunocompromise, participation in another clinical research study, and preschool pertussis booster vaccination received less than one year previously. Main outcome measures Evidence of recent pertussis infection based on an oral fluid anti-pertussis toxin IgG titre of at least 70 arbitrary units. Cough frequency was measured in six children with laboratory confirmed pertussis. Results 56 (20%, 95% confidence interval 16% to 25%) children had evidence of recent pertussis infection, including 39 (18%, 13% to 24%) of 215 children who had been fully vaccinated. The risk of pertussis was more than three times higher (21/53; 40%, 26% to 54%) in children who had received the preschool pertussis booster vaccination seven years or more previously than in those who had received it less than seven years previously (20/171; 12%, 7% to 17%). The risk of pertussis was similar between children who received five and three component preschool pertussis booster vaccines (risk ratio for five component vaccine 1.14, 0.64 to 2.03). Four of six children in whom cough frequency was measured coughed more than 400 times in 24 hours. Conclusions Pertussis can still be found in a fifth of school age children who present in primary care with persistent cough and can cause clinically significant cough in fully vaccinated children. These findings will help to inform consideration of the need for an adolescent pertussis booster vaccination in the United Kingdom. Study registration UK Clinical Research Network portfolio ID 8361.

Background: Postinfectious cough is common in primary care, but has no proven effective treatments. Cysteinyl leukotrienes are involved in the pathogenesis of postinfectious cough and whooping cough (pertussis). We investigated the effectiveness of montelukast, a cysteinyl leukotriene receptor antagonist, in the treatment of postinfectious cough. Methods: In this randomised, placebo-controlled trial, non-smoking adults aged 16-49 years with postinfectious cough of 2-8 weeks' duration were recruited from 25 general practices in England. Patients were tested for pertussis (oral fluid anti-pertussis toxin IgG) and randomly assigned (1:1) to montelukast 10 mg daily or image-matched placebo for 2 weeks. Patients chose whether to continue study drug for another 2 weeks. The randomisation sequence was computer-generated and stratified by general practice. Patients, health-care professionals, and researchers were masked to treatment allocation. Effectiveness was assessed with the Leicester Cough Questionnaire to measure changes in cough-specific quality of life; the primary outcomes were changes in total score between baseline and two follow-up stages (2 weeks and 4 weeks). The primary analysis was by intention to treat with imputation by last observation carried forward. Recruitment closed on Sept 21, 2012, and follow-up has been completed. This trial is registered with EudraCT (2010-019647-19), UKCRN Portfolio (ID 8360), and ClinicalTrials.gov (NCT01279668). Findings: From April 13, 2011, to Sept 21, 2012, we randomly assigned 276 patients to montelukast (n=137) or placebo (n=139). 70 (25%) patients had laboratory-confirmed pertussis. Improvements in cough-specific quality of life occurred in both groups after 2 weeks (montelukast: mean 2·7, 95% CI 2·2-3·3; placebo: 3·6, 2·9-4·3), but the difference between groups did not meet the minimum clinically important difference of 1·3 (mean difference -0·9, -1·7 to -0·04, p=0·04). This difference was not statistically significant in any sensitivity analyses. After 2 weeks, 192 of 259 participants from whom data were available elected to continue study drug (99 [77%] of 129 participants on montelukast; 93 [72%] of 130 on placebo). After 4 weeks, there were no significant between-group differences in cough-specific quality of life improvement (montelukast: 5·2, 4·5-5·9; placebo: 5·9, 5·1-6·7; mean difference -0·5, -1·5 to 0·6, p=0·38) or adverse event rates (21 (15%) of 137 patients on montelukast reported one or more adverse events; 31 (22%) of 139 on placebo; p=0·14). The most common adverse events reported were increased mucus production (montelukast, n=6; placebo, n=2), gastrointestinal disturbance (montelukast, n=3; placebo, n=5), and headache (montelukast, n=2; placebo, n=6). One serious adverse event was reported (placebo, n=1), which was unrelated to study drug (shortness of breath and throat tightness after severe coughing bouts). Interpretation: Montelukast is not an effective treatment for postinfectious cough. However, the burden of postinfectious cough in primary care is high, making it an ideal setting for future antitussive treatment trials. Funding: National Institute for Health Research School for Primary Care Research, UK. © 2014 Wang et al.

Background: During epidemics, influenza attack rates in children may exceed 40%. Options for prevention and treatment currently include the neuraminidase inhibitors zanamivir and oseltamivir. Laninamivir octanoate, the prodrug of laninamivir, is currently being developed. Objectives: To assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prevention of influenza in children. Search methods: For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1) which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January week 2, 2011) and EMBASE (January 2010 to January 2011). Selection criteria: Double-blind, randomised controlled trials (RCTs) comparing neuraminidase inhibitors with placebo or other antiviral drugs in children aged up to and including 12 years. We also included safety and tolerability data from other types of studies. Data collection and analysis: Four review authors selected studies, assessed study quality and extracted data for the current and previous versions of this review. We analysed data separately for oseltamivir versus placebo, zanamivir versus placebo and laninamivir octanoate versus oseltamivir. Main results: Six treatment trials involving 1906 children with clinical influenza and 450 children with influenza diagnosed on rapid near-patient influenza testing were included. Of these 2356 children, 1255 had laboratory-confirmed influenza. Three prophylaxis trials involving 863 children exposed to influenza were also included. In children with laboratory-confirmed influenza oseltamivir reduced median duration of illness by 36 hours (26%, P < 0.001). One trial of oseltamivir in children with asthma who had laboratory-confirmed influenza showed only a small reduction in illness duration (10.4 hours, 8%), which was not statistically significant (P = 0.542). Laninamivir octanoate 20 mg reduced symptom duration by 2.8 days (60%, P < 0.001) in children with oseltamivir-resistant influenza A/H1N1. Zanamivir reduced median duration of illness by 1.3 days (24%, P < 0.001). Oseltamivir significantly reduced acute otitis media in children aged one to five years with laboratory-confirmed influenza (risk difference (RD) -0.14, 95% confidence interval (CI) -0.24 to -0.04). Prophylaxis with either zanamivir or oseltamivir was associated with an 8% absolute reduction in developing influenza after the introduction of a case into a household (RD -0.08, 95% CI -0.12 to -0.05, P < 0.001). The adverse event profile of zanamivir was no worse than placebo but vomiting was more commonly associated with oseltamivir (number needed to harm = 17, 95% CI 10 to 34). The adverse event profiles of laninamivir octanoate and oseltamivir were similar. Authors' conclusions: Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir-resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high-quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups. © 2012 The Cochrane Collaboration.

Background: Mycoplasma pneumoniae (M. pneumoniae) is a significant cause of community‐acquired pneumonia in children and adolescents. Treatment with macrolide antibiotics is recommended. However, M. pneumoniae is difficult to diagnose based on clinical symptoms and signs. Diagnostic uncertainty can lead to inappropriate antibiotic prescribing, which may worsen clinical prognosis and increase antibiotic resistance. Objectives: The objectives of this review are (i) to assess the diagnostic accuracy of symptoms and signs in the clinical recognition of M. pneumoniae in children and adolescents with community‐acquired pneumonia; and (ii) to assess the influence of potential sources of heterogeneity on the diagnostic accuracy of symptoms and signs in the clinical recognition of M. pneumoniae. Search methods: We searched MEDLINE (January 1950 to 26 June 2012) and EMBASE (January 1980 to 26 June 2012). We identified additional references by handsearching the reference lists of included articles and snowballing. We searched the reference lists of relevant systematic reviews identified by searching the Medion database, Database of Reviews of Effects 2012, Issue 6 (25 June 2012) and the Cochrane Register of Diagnostic Test Accuracy studies (2 July 2012). Experts in the field reviewed our list of included studies for any obvious omissions. Selection criteria: We included peer‐reviewed published studies which prospectively and consecutively recruited children with community‐acquired pneumonia from any healthcare setting, confirmed the presence of M. pneumoniae using serology with or without other laboratory methods and reported data on clinical symptoms and signs in sufficient detail to construct 2 x 2 tables. Data collection and analysis: One review author scanned titles to exclude obviously irrelevant articles. Two review authors independently scanned the remaining titles and abstracts, reviewed full‐text versions of potentially relevant articles, assessed the quality of included articles and extracted data on study characteristics and the following clinical features: cough, wheeze, coryza, crepitations, fever, rhonchi, shortness of breath, chest pain, diarrhea, myalgia and headache. We calculated study‐specific values for sensitivity, specificity and positive and negative likelihood ratios with 95% confidence intervals (CIs). We estimated the post‐test probability of M. pneumoniae based on the absence or presence of symptoms and signs. We calculated pooled sensitivities, specificities, positive and negative likelihood ratios with 95% CIs for symptoms and signs where data were reported by at least four included studies by fitting a bivariate normal model for the logit transforms of sensitivity and specificity. We explored potential sources of heterogeneity by fitting bivariate models with covariates using multi‐level mixed‐effects logistic regression. We performed sensitivity analyses excluding data from studies for which we were concerned about the representativeness of the study population and/or the acceptability of the reference standard. Main results: Our search identified 8299 articles (excluding duplicates). We examined the titles and abstracts of 1125 articles and the full‐text versions of 97 articles. We included seven studies in our review, which reported data from 1491 children; all were conducted in hospital settings. Overall, study quality was moderate. In two studies the presence of chest pain more than doubled the probability of M. pneumoniae. Wheeze was 12% more likely to be absent in children with M. pneumoniae (pooled positive likelihood ratio (LR+) 0.76, 95% CI 0.60 to 0.97; pooled negative likelihood ratio (LR‐) 1.12, 95% CI 1.02 to 1.23). Our sensitivity analysis showed that the presence of crepitations was associated with M. pneumoniae, but this finding was of borderline statistical significance (pooled LR+ 1.10, 95% CI 0.99 to 1.23; pooled LR‐ 0.66, 95% CI 0.46 to 0.96). Authors' conclusions: M. pneumoniae cannot be reliably diagnosed in children and adolescents with community‐acquired pneumonia based on clinical symptoms and signs. Although the absence of wheeze is a statistically significant diagnostic indicator, it does not have sufficient diagnostic value to guide empirical macrolide treatment. Data from two studies suggest that the presence of chest pain more than doubles the probability of M. pneumoniae. However, further research is needed to substantiate this finding. More high quality large‐scale studies in primary care settings are needed to help develop prediction rules based on epidemiological data as well as clinical and baseline patient characteristics.

Background: During epidemics, influenza attack rates in children may exceed 40%. Options for prevention and treatment currently include the neuraminidase inhibitors zanamivir and oseltamivir. Laninamivir octanoate, the prodrug of laninamivir, is currently being developed. Objectives: To assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prevention of influenza in children. Search methods: For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1) which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January week 2, 2011) and EMBASE (January 2010 to January 2011). Selection criteria: Double‐blind, randomised controlled trials (RCTs) comparing neuraminidase inhibitors with placebo or other antiviral drugs in children aged up to and including 12 years. We also included safety and tolerability data from other types of studies. Data collection and analysis: Four review authors selected studies, assessed study quality and extracted data for the current and previous versions of this review. We analysed data separately for oseltamivir versus placebo, zanamivir versus placebo and laninamivir octanoate versus oseltamivir. Main results: Six treatment trials involving 1906 children with clinical influenza and 450 children with influenza diagnosed on rapid near‐patient influenza testing were included. Of these 2356 children, 1255 had laboratory‐confirmed influenza. Three prophylaxis trials involving 863 children exposed to influenza were also included. In children with laboratory‐confirmed influenza oseltamivir reduced median duration of illness by 36 hours (26%, P < 0.001). One trial of oseltamivir in children with asthma who had laboratory‐confirmed influenza showed only a small reduction in illness duration (10.4 hours, 8%), which was not statistically significant (P = 0.542). Laninamivir octanoate 20 mg reduced symptom duration by 2.8 days (60%, P < 0.001) in children with oseltamivir‐resistant influenza A/H1N1. Zanamivir reduced median duration of illness by 1.3 days (24%, P < 0.001). Oseltamivir significantly reduced acute otitis media in children aged one to five years with laboratory‐confirmed influenza (risk difference (RD) ‐0.14, 95% confidence interval (CI) ‐0.24 to ‐0.04). Prophylaxis with either zanamivir or oseltamivir was associated with an 8% absolute reduction in developing influenza after the introduction of a case into a household (RD ‐0.08, 95% CI ‐0.12 to ‐0.05, P < 0.001). The adverse event profile of zanamivir was no worse than placebo but vomiting was more commonly associated with oseltamivir (number needed to harm = 17, 95% CI 10 to 34). The adverse event profiles of laninamivir octanoate and oseltamivir were similar. Authors' conclusions: Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir‐resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high‐quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups.