Kay Wang

Identification of children at risk of influenza-related complications in primary and ambulatory care: a systematic review and meta-analysis

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 We requested unpublished data from investigators of studies that had obtained, but not published, relevant data.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<0·0001). 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.

Whooping cough in school age children presenting with persistent cough in UK primary care after introduction of the preschool pertussis booster vaccination: prospective cohort study.

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.

Mycoplasma pneumoniae and respiratory virus infections in children with persistent cough in England: a retrospective analysis.

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.

Foreign body inhalation in children

Children, especially toddlers, tend to place objects in their mouths while exploring their environment. They are therefore at increased risk of inhaling foreign bodies, which may become lodged in the tracheobronchial system. #### Case scenario A 2 year old boy presented to his general practitioner with a two week history of a dry, persistent cough. His mother recalled an episode two weeks ago when he had a violent coughing fit while eating nuts and raisins. She took him to the nearest hospital emergency department, but he was discharged a few hours later after a normal physical examination and normal chest radiograph. Nevertheless, this history of persistent cough following a choking episode should raise concern about possible foreign body inhalation. #### How common is it? Diagnosis of an inhaled foreign body was delayed by more than a week in 29% of cases …

Pertussis-induced cough.

Pertussis (whooping cough) is one of the commonest vaccine preventable diseases in the UK, despite vaccination coverage being maintained for the last 15 years at over 90% among infants and the addition of a pre-school booster to the UK national immunisation programme in 2001. However, it is known that pertussis vaccine does not confer long-term immunity to clinical infection. Evidence of pertussis infection has been reported in 37% of children presenting in UK primary care and 20% of adolescents and adults presenting in Canadian health centres with persistent cough. In children and adults with persistent cough, paroxysmal coughing is the most sensitive indicator of pertussis, but has poor specificity and limited diagnostic value. Vomiting and whooping, particularly in combination, are stronger predictors of pertussis. Cough duration is longer in children than in adults with pertussis (median cough duration 112 days versus 42 days); individuals may take even longer to recover fully and regain previous levels of exercise tolerance. A diagnosis of pertussis may be confirmed by culture, Polymerase Chain Reaction (PCR) or serology. Single estimates of anti-pertussis toxin (PT) antibody titres in blood or oral fluid samples are highly specific. There are currently no proven efficacious treatments for pertussis-induced cough. Treatment with macrolide antibiotics reduces the duration of an individuals infectious period, but does not alter the duration of cough. Further research is needed to re-examine the epidemiology of pertussis in countries with different vaccination schedules, find efficacious treatments and develop methods of measuring cough frequency and severity in patients with pertussis-induced cough.

Non-contact infrared thermometers for measuring temperature in children: primary care diagnostic technology update.

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 …

Prescribing antibiotics to 'at-risk' children with influenza-like illness in primary care: qualitative study.

Objectives National Institute for Health and Care Excellence guidelines recommend immediate antibiotic treatment of respiratory tract infections in ‘at-risk’ individuals with comorbidities. Observational evidence suggests that influenza particularly predisposes children to bacterial complications. This study investigates general practitioners’ (GPs’) accounts of factors influencing their decision-making about antibiotic prescribing in the management of at-risk children with influenza-like illness (ILI). Design Qualitative interview study using a maximum variation sample with thematic analysis through constant comparison. Setting Semistructured telephone interviews with UK GPs using a case vignette of a child with comorbidities presenting with ILI. Participants There were 41 GPs (41.5% men; 40 from England, 1 from Northern Ireland) with a range of characteristics including length of time in practice, paediatrics experience, practice setting and deprivation. Results There was considerable uncertainty and variation in the way GPs responded to the case and difference of opinion about how long-term comorbidities should affect their antibiotic prescribing pattern. Factors influencing their decision included the childs case history and clinical examination; the GPs view of the parents ability to self-manage; the GPs own confidence and experiences of managing sick children and assessment of individual versus abstract risk. GPs rarely mentioned potential influenza infection or asked about immunisation status. All said that they would want to see the child; views about delayed prescribing varied in relation to local health service provision including options for follow-up and paediatric services. Conclusions The study demonstrates diagnostic uncertainty and wide variation in GP decision-making about prescribing antibiotics to children with comorbidity. Future guidelines might encourage consideration of a specific diagnosis such as influenza, and risk assessment tools could be developed to allow clinicians to quantify the levels of risk associated with different types of comorbidity. However, the wide range of clinical and non-clinical factors involved in decision-making during these consultations should also be considered in future guidelines.

Effect of Oral Prednisolone on Symptom Duration and Severity in Nonasthmatic Adults With Acute Lower Respiratory Tract Infection: A Randomized Clinical Trial

Importance Acute lower respiratory tract infection is common and often treated inappropriately in primary care with antibiotics. Corticosteroids are increasingly used but without sufficient evidence. Objective To assess the effects of oral corticosteroids for acute lower respiratory tract infection in adults without asthma. Design, Setting, and Participants Multicenter, 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. Interventions Two 20-mg prednisolone tablets (n = 199) or matched placebo (n = 202) once daily for 5 days. Main Outcomes and Measures The 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. Results Among 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 &agr; = .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 &agr; = .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 Relevance Oral 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 Registration ISRCTN.com Identifier: ISRCTN57309858

Cough management in primary, secondary and tertiary settings

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.

Early use of Antibiotics for at Risk CHildren with InfluEnza (ARCHIE): protocol for a double-blind, randomised, placebo-controlled trial.

Introduction Influenza 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 analysis The 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. Ethics The 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 numbers ISRCTN 70714783; Pre-results. EudraCT 2013-002822-21; Pre-results.