Risk of Myocarditis After Sequential Doses of COVID-19 Vaccine and SARS-CoV-2 Infection by Age and Sex.

BACKGROUND: Myocarditis is more common after severe acute respiratory syndrome coronavirus 2 infection than after COVID-19 vaccination, but the risks in younger people and after sequential vaccine doses are less certain. METHODS: A self-controlled case series study of people ages 13 years or older vaccinated for COVID-19 in England between December 1, 2020, and December 15, 2021, evaluated the association between vaccination and myocarditis, stratified by age and sex. The incidence rate ratio and excess number of hospital admissions or deaths from myocarditis per million people were estimated for the 1 to 28 days after sequential doses of adenovirus (ChAdOx1) or mRNA-based (BNT162b2, mRNA-1273) vaccines, or after a positive SARS-CoV-2 test. RESULTS: In 42 842 345 people receiving at least 1 dose of vaccine, 21 242 629 received 3 doses, and 5 934 153 had SARS-CoV-2 infection before or after vaccination. Myocarditis occurred in 2861 (0.007%) people, with 617 events 1 to 28 days after vaccination. Risk of myocarditis was increased in the 1 to 28 days after a first dose of ChAdOx1 (incidence rate ratio, 1.33 [95% CI, 1.09-1.62]) and a first, second, and booster dose of BNT162b2 (1.52 [95% CI, 1.24-1.85]; 1.57 [95% CI, 1.28-1.92], and 1.72 [95% CI, 1.33-2.22], respectively) but was lower than the risks after a positive SARS-CoV-2 test before or after vaccination (11.14 [95% CI, 8.64-14.36] and 5.97 [95% CI, 4.54-7.87], respectively). The risk of myocarditis was higher 1 to 28 days after a second dose of mRNA-1273 (11.76 [95% CI, 7.25-19.08]) and persisted after a booster dose (2.64 [95% CI, 1.25-5.58]). Associations were stronger in men younger than 40 years for all vaccines. In men younger than 40 years old, the number of excess myocarditis events per million people was higher after a second dose of mRNA-1273 than after a positive SARS-CoV-2 test (97 [95% CI, 91-99] versus 16 [95% CI, 12-18]). In women younger than 40 years, the number of excess events per million was similar after a second dose of mRNA-1273 and a positive test (7 [95% CI, 1-9] versus 8 [95% CI, 6-8]). CONCLUSIONS: Overall, the risk of myocarditis is greater after SARS-CoV-2 infection than after COVID-19 vaccination and remains modest after sequential doses including a booster dose of BNT162b2 mRNA vaccine. However, the risk of myocarditis after vaccination is higher in younger men, particularly after a second dose of the mRNA-1273 vaccine.

Antibiotics for lower respiratory tract infection in children presenting in primary care in England (ARTIC PC): a double-blind, randomised, placebo-controlled trial.

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. FUNDING: National Institute for Health Research.

The early use of Antibiotics for at Risk CHildren with InfluEnza-like illness (ARCHIE): a double-blind randomised placebo-controlled trial.

INTRODUCTION: The 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. RESULTS: We 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. CONCLUSION: Our 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.

Death audits and reviews for reducing maternal, perinatal and child mortality.

BACKGROUND: The United Nations' Sustainable Development Goals (SDGs) include reducing the global maternal mortality rate to less than 70 per 100,000 live births and ending preventable deaths of newborns and children under five years of age, in every country, by 2030. Maternal and perinatal death audit and review is widely recommended as an intervention to reduce maternal and perinatal mortality, and to improve quality of care, and could be key to attaining the SDGs. However, there is uncertainty over the most cost-effective way of auditing and reviewing deaths: community-based audit (verbal and social autopsy), facility-based audits (significant event analysis (SEA)) or a combination of both (confidential enquiry). OBJECTIVES: To assess the impact and cost-effectiveness of different types of death audits and reviews in reducing maternal, perinatal and child mortality. SEARCH METHODS: We searched the following from inception to 16 January 2019: CENTRAL, Ovid MEDLINE, Embase OvidSP, and five other databases. We identified ongoing studies using ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform, and searched reference lists of included articles. SELECTION CRITERIA: Cluster-randomised trials, cluster non-randomised trials, controlled before-and-after studies and interrupted time series studies of any form of death audit or review that involved reviewing individual cases of maternal, perinatal or child deaths, identifying avoidable factors, and making recommendations. To be included in the review, a study needed to report at least one of the following outcomes: perinatal mortality rate; stillbirth rate; neonatal mortality rate; mortality rate in children under five years of age or maternal mortality rate. DATA COLLECTION AND ANALYSIS: We used standard Cochrane Effective Practice and Organisation of Care (EPOC) group methodological procedures. Two review authors independently extracted data, assessed risk of bias and assessed the certainty of the evidence using GRADE. We planned to perform a meta-analysis using a random-effects model but included studies were not homogeneous enough to make pooling their results meaningful. MAIN RESULTS: We included two cluster-randomised trials. Both introduced death review and audit as part of a multicomponent intervention, and compared this to current care. The QUARITE study (QUAlity of care, RIsk management, and TEchnology) concerned maternal death reviews in hospitals in West Africa, which had very high maternal and perinatal mortality rates. In contrast, the OPERA trial studied perinatal morbidity/mortality conferences (MMCs) in maternity units in France, which already had very low perinatal mortality rates at baseline. The OPERA intervention in France started with an outreach visit to brief obstetricians, midwives and anaesthetists on the national guidelines on morbidity/mortality case management, and was followed by a series of perinatal MMCs. Half of the intervention units were randomised to receive additional support from a clinical psychologist during these meetings. The OPERA intervention may make little or no difference to overall perinatal mortality (low certainty evidence), however we are uncertain about the effect of the intervention on perinatal mortality related to suboptimal care (very low certainty evidence).The intervention probably reduces perinatal morbidity related to suboptimal care (unadjusted odds ratio (OR) 0.62, 95% confidence interval (CI) 0.40 to 0.95; 165,353 births; moderate-certainty evidence). The effect of the intervention on stillbirth rate, neonatal mortality, mortality rate in children under five years of age, maternal mortality or adverse effects was not reported. The QUARITE intervention in West Africa focused on training leaders of hospital obstetric teams using the ALARM (Advances in Labour And Risk Management) course, which included one day of training about conducting maternal death reviews. The leaders returned to their hospitals, established a multidisciplinary committee and started auditing maternal deaths, with the support of external facilitators. The intervention probably reduces inpatient maternal deaths (adjusted OR 0.85, 95% CI 0.73 to 0.98; 191,167 deliveries; moderate certainty evidence) and probably also reduces inpatient neonatal mortality within 24 hours following birth (adjusted OR 0.74, 95% CI 0.61 to 0.90; moderate certainty evidence). However, QUARITE probably makes little or no difference to the inpatient stillbirth rate (moderate certainty evidence) and may make little or no difference to the inpatient neonatal mortality rate after 24 hours, although the 95% confidence interval includes both benefit and harm (low certainty evidence). The QUARITE intervention probably increases the percent of women receiving high quality of care (OR 1.87, 95% CI 1.35 - 2.57, moderate-certainty evidence). The effect of the intervention on perinatal mortality, mortality rate in children under five years of age, or adverse effects was not reported. We did not find any studies that evaluated child death audit and review or community-based death reviews or costs. AUTHORS' CONCLUSIONS: A complex intervention including maternal death audit and review, as well as development of local leadership and training, probably reduces inpatient maternal mortality in low-income country district hospitals, and probably slightly improves quality of care. Perinatal death audit and review, as part of a complex intervention with training, probably improves quality of care, as measured by perinatal morbidity related to suboptimal care, in a high-income setting where mortality was already very low. The WHO recommends that maternal and perinatal death reviews should be conducted in all hospitals globally. However, conducting death reviews in isolation may not be sufficient to achieve the reductions in mortality observed in the QUARITE trial. This review suggests that maternal death audit and review may need to be implemented as part of an intervention package which also includes elements such as training of a leading doctor and midwife in each hospital, annual recertification, and quarterly outreach visits by external facilitators to provide supervision and mentorship. The same may also apply to perinatal and child death reviews. More operational research is needed on the most cost-effective ways of implementing maternal, perinatal and paediatric death reviews in low- and middle-income countries.

Home deaths of children under 5 years in rural South Africa: a population-based longitudinal study.

OBJECTIVES: To determine the proportion of under-5 deaths that occurred at home in rural South Africa, whether care was sought prior to death, and determinants of home deaths amongst those who sought care. METHODS: Verbal autopsy data were used for all under-5 deaths, 2000-2015, in two health and demographic surveillance system sites. Trends in place of death and care-seeking were assessed. Associations between sociodemographic factors and home death despite seeking care were assessed by multivariate logistic regressions. RESULTS: There were 3760 under-5 deaths; 1954 (53%) at home and 1510 (41%) in health facilities. Eighty-four per cent of children who died at home accessed healthcare during their final illness. Amongst neonates for whom care was sought, those who were 8-27 days old were more likely to die at home than those who were 0-7 days old (OR = 5.56, 95%CI 2.69-11.55, P < 0.001). Factors associated with home death of infants and young children despite seeking care included low maternal education (OR = 1.71, 95%CI 1.31-2.24, P < 0.001), larger household size (OR = 1.56, 95%CI 1.17-2.06, P = 0.002), traditional medicine use (OR = 2.33, 95%CI 1.75-3.12, P < 0.001) and Mozambican descent (OR = 1.47, 95%CI 1.06-2.03, P = 0.020). The proportion of HIV-related deaths that occurred at home fell from 60% in 2008-2011 to 39% in 2012-2015 ( χ2  = 13.86, P < 0.001). CONCLUSION: More than half of under-5 deaths in rural South Africa occurred at home although healthcare was sought for most children, highlighting that home deaths are not simply a function of poor care-seeking. Interventions should target high-risk sociodemographic groups.

OBJECTIFS: Déterminer la proportion de décès d'enfants de moins de 5 ans survenus à domicile dans les zones rurales d'Afrique du Sud, si des soins ont été recherchés avant le décès et les déterminants des décès à domicile chez ceux qui ont recherché des soins. MÉTHODES: Les données d'autopsie verbale ont été utilisées pour tous les décès d'enfants de moins de 5 ans entre 2000 et 2015, dans deux sites du système de surveillance démographique et de santé. Les tendances en matière de lieu de décès et de recherche de soins ont été évaluées. Les associations entre les facteurs sociodémographiques et le décès à domicile malgré les soins recherchés ont été évaluées par des régressions logistiques multivariées. RÉSULTATS: Il y a eu 3.760 décès de moins de 5 ans; 1.954 (53%) à domicile et 1.510 (41%) dans les établissements de santé. 84% des enfants décédés à domicile ont eu accès à des soins de santé au cours de leur dernière maladie. Parmi les nouveau-nés pour lesquels des soins ont été recherchés, ceux âgés de 8 à 27 jours étaient plus susceptibles de mourir à domicile que ceux âgés de 0 à 7 jours (OR = 5,56; IC95% 2,69-11,55; p <0,001). Les facteurs associés au décès des nourrissons et des jeunes enfants à domicile malgré la recherche de soins comprenaient un niveau d'éducation maternelle faible (OR = 1,71; IC95%: 1,31-2,24; p <0,001), une taille du ménage plus grande (OR = 1,56; IC95%: 1,17-2,06; p = 0,002), l'utilisation de la médecine traditionnelle (OR = 2,33; IC95%: 1,75-3,12; p <0,001) et l'origine mozambicaine (OR = 1,47; IC95%: 1,06-2,03; p = 0,020). La proportion de décès liés au VIH survenus à domicile est passée de 60% en 2008-2011 à 39% en 2012-2015 (Chi2 = 13,86; p <0,001). CONCLUSION: Plus de la moitié des décès des moins de 5 ans dans les zones rurales d'Afrique du Sud sont survenus à domicile bien que pour la plupart des enfants une recherche de soins de santé a été effectuée, soulignant que les décès à domicile ne sont pas simplement liés à un mauvais recours aux soins. Les interventions devraient cibler les groupes sociodémographiques à haut risque.

Preference-based measures to obtain health state utility values for use in economic evaluations with child-based populations: a review and UK-based focus group assessment of patient and parent choices.

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.

Hospital readmissions with acute infectious diseases in New Zealand children < 2 years of age.

BACKGROUND: Infectious diseases are the leading cause of hospital admissions in young children. Hospitalisation with an infectious disease is a recurrent event for some children. Our objective was to describe risk factors for infectious disease readmission following hospital admission with an infectious disease in the first two years of life. METHODS: We performed a national cohort study of New Zealand children, born 2005-2009, with an infectious disease admission before age 24 months. Children readmitted with an infectious disease within 12 months of the first infectious disease admission were identified. Every infectious disease admission was categorised as a respiratory, enteric, skin and soft tissue, urinary or other infection. Independent associations of demographic and child health factors with infectious disease readmission were determined using multiple variable logistic regression. RESULTS: From 2005 to 2011, there were 69,902 infectious disease admissions for 46,657 children less than two years old. Of these 46,657 children, 10,205 (22%) had at least one infectious disease readmission within 12 months of their first admission. The first infectious disease admission was respiratory (54%), enteric (15%), skin or soft tissue (7%), urinary (4%) or other (20%). Risk of infectious disease readmission was increased if the first infectious disease admission was respiratory (OR = 1.87, 95% CI 1.78-1.95) but not if it was in any other infectious disease category. Risk factors for respiratory infectious disease readmission were male gender, Pacific or Maori ethnicity, greater household deprivation, presence of a complex chronic condition, or a first respiratory infectious disease admission during autumn or of ≥3 days duration. Fewer factors (younger age, male gender, presence of a complex chronic condition) were associated with enteric infection readmission. The presence of a complex chronic condition was the only factor associated with urinary tract infection readmission and none of the factors were associated with skin or soft tissue infection readmission. CONCLUSIONS: In children less than two years old, infectious disease readmission risk is increased if the first infectious disease admission is a respiratory infectious disease but not if it is another infectious disease category. Risk factors for respiratory infectious disease readmission are different from those for other infectious disease readmissions.

Ethnic disparities in infectious disease hospitalisations in the first year of life in New Zealand.

AIM: Infectious disease (ID) hospitalisation rates are increasing in New Zealand (NZ), especially in pre-school children, and Maori and Pacific people. We aimed to identify risk factors for ID hospitalisation in infancy within a birth cohort of NZ children, and to identify differences in risk factors between ethnic groups. METHODS: We investigated an established cohort of 6846 NZ children, born in 2009-2010, with linkage to a national data set of hospitalisations. We used multivariable logistic regression to obtain odds ratios (OR) for factors associated with ID hospitalisation in the first year of life, firstly for all children, and then separately for Maori or Pacific children. RESULTS: In the whole cohort, factors associated with ID hospitalisation were Maori (OR: 1.49, 95% CI: 1.17-1.89) or Pacific (2.51; 2.00-3.15) versus European maternal ethnicity, male gender (1.32; 1.13-1.55), low birthweight (1.94, 1.39-2.66), exclusive breastfeeding for <4 months (1.22, 1.04-1.43), maternal experience of health-care racism (1.60, 1.19-2.12), household deprivation (most vs. least deprived quintile of households (1.50, 1.12-2.02)), day-care attendance (1.43, 1.12-1.81) and maternal smoking (1.55, 1.26-1.91). Factors associated with ID hospitalisation for Maori infants were high household deprivation (2.16, 1.06-5.02) and maternal smoking (1.48, 1.02-2.14); and for Pacific infants were delayed immunisation (1.72, 1.23-2.38), maternal experience of health-care racism (2.20, 1.29-3.70) and maternal smoking (1.59, 1.10-2.29). CONCLUSIONS: Maori and Pacific children in NZ experience a high burden of ID hospitalisation. Some risk factors, for example maternal smoking, are shared, while others are ethnic-specific. Interventions aimed at preventing ID hospitalisations should address both shared and ethnic-specific factors.

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 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 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.

Effect of nasal balloon autoinflation in children with otitis media with effusion in primary care: an open randomized controlled trial.

BACKGROUND: Otitis media with effusion is a common problem that lacks an evidence-based nonsurgical treatment option. We assessed the clinical effectiveness of treatment with a nasal balloon device in a primary care setting. METHODS: We conducted an open, pragmatic randomized controlled trial set in 43 family practices in the United Kingdom. Children aged 4-11 years with a recent history of ear symptoms and otitis media with effusion in 1 or both ears, confirmed by tympanometry, were allocated to receive either autoinflation 3 times daily for 1-3 months plus usual care or usual care alone. Clearance of middle-ear fluid at 1 and 3 months was assessed by experts masked to allocation. RESULTS: Of 320 children enrolled, those receiving autoinflation were more likely than controls to have normal tympanograms at 1 month (47.3% [62/131] v. 35.6% [47/132]; adjusted relative risk [RR] 1.36, 95% confidence interval [CI] 0.99 to 1.88) and at 3 months (49.6% [62/125] v. 38.3% [46/120]; adjusted RR 1.37, 95% CI 1.03 to 1.83; number needed to treat = 9). Autoinflation produced greater improvements in ear-related quality of life (adjusted between-group difference in change from baseline in OMQ-14 [an ear-related measure of quality of life] score -0.42, 95% CI -0.63 to -0.22). Compliance was 89% at 1 month and 80% at 3 months. Adverse events were mild, infrequent and comparable between groups. INTERPRETATION: Autoinflation in children aged 4-11 years with otitis media with effusion is feasible in primary care and effective both in clearing effusions and improving symptoms and ear-related child and parent quality of life. TRIAL REGISTRATION: ISRCTN, No. 55208702.

Symptomatic treatment of the cough in whooping cough.

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.

Safety outcomes following COVID-19 vaccination and infection in 5.1 million children in England.

The risk-benefit profile of COVID-19 vaccination in children remains uncertain. A self-controlled case-series study was conducted using linked data of 5.1 million children in England to compare risks of hospitalisation from vaccine safety outcomes after COVID-19 vaccination and infection. In 5-11-year-olds, we found no increased risks of adverse events 1-42 days following vaccination with BNT162b2, mRNA-1273 or ChAdOX1. In 12-17-year-olds, we estimated 3 (95%CI 0-5) and 5 (95%CI 3-6) additional cases of myocarditis per million following a first and second dose with BNT162b2, respectively. An additional 12 (95%CI 0-23) hospitalisations with epilepsy and 4 (95%CI 0-6) with demyelinating disease (in females only, mainly optic neuritis) were estimated per million following a second dose with BNT162b2. SARS-CoV-2 infection was associated with increased risks of hospitalisation from seven outcomes including multisystem inflammatory syndrome and myocarditis, but these risks were largely absent in those vaccinated prior to infection. We report a favourable safety profile of COVID-19 vaccination in under-18s.

"People don't have the answers": A qualitative exploration of the experiences of young people with Long COVID.

Young people living with Long COVID are learning to navigate life with a constellation of poorly understood symptoms. Most qualitative studies on experiences living with Long COVID focus on adult populations. This study aimed to understand the experiences of young people living with Long COVID. Qualitative, semi-structured interviews were conducted (n = 16); 11 young people (aged 13-19) and five parents were recruited from the Children and Young People with Long COVID (CLoCk) study (n = 11) or its patient and public involvement and engagement (PPIE) group (n = 5). Thematic analysis generated four themes: (i) Unravelling Long COVID: Exploring Symptom Journeys and Diagnostic Dilemmas; (ii) Identity Disruption and Adjustment; (iii) Long COVID's Ripple Effect: the impact on Mental Health, Connections, and Education; and (iv) Navigating Long COVID: barriers to support and accessing services. Treatment options were perceived as not widely available or ineffective, emphasising the need for viable and accessible interventions for young people living with Long COVID.

Why was the study done? Capturing the broad impact of Long COVID and the experiences of young people and their families living with persisting symptoms will help to identify the unique needs and challenges experienced by this population and help shape effective treatments going forward. What did the researchers do? Researchers conducted interviews with children and young people living with Long COVID. Parents of young people were also invited to participate to gain a comprehensive understanding of the effects of Long COVID and its impact on the wider family. What did the researchers find? Analysis of 11 interviews with young people and 5 with parents revealed four themes central to young people's experiences of living with Long COVID relating to unknowns and uncertainties, identity shifts, the impact of symptoms and accessing support. What do findings mean? Findings from the study suggest the implications of Long COVID were far-reaching and impairing. Current treatment options were not perceived as widely available or effective, suggesting a need for further research to develop effective interventions for young people living with Long COVID.

Antibiotics for lower respiratory tract infection in children presenting in primary care: ARTIC-PC RCT.

Background: Antimicrobial resistance is a global health threat. Antibiotics are commonly prescribed for children with uncomplicated lower respiratory tract infections, but there is little randomised evidence to support the effectiveness of antibiotics in treating these infections, either overall or relating to key clinical subgroups in which antibiotic prescribing is common (chest signs; fever; physician rating of unwell; sputum/rattly chest; shortness of breath). Objectives: To estimate the clinical effectiveness and cost-effectiveness of amoxicillin for uncomplicated lower respiratory tract infections in children both overall and in clinical subgroups. Design: Placebo-controlled trial with qualitative, observational and cost-effectiveness studies. Setting: UK general practices. Participants: Children aged 1-12 years with acute uncomplicated lower respiratory tract infections. Outcomes: The primary outcome was the duration in days of symptoms rated moderately bad or worse (measured using a validated diary). Secondary outcomes were symptom severity on days 2-4 (0 = no problem to 6 = as bad as it could be); symptom duration until very little/no problem; reconsultations for new or worsening symptoms; complications; side effects; and resource use. Methods: Children were randomised to receive 50 mg/kg/day of oral amoxicillin in divided doses for 7 days, or placebo using pre-prepared packs, using computer-generated random numbers by an independent statistician. Children who were not randomised could participate in a parallel observational study. Semistructured telephone interviews explored the views of 16 parents and 14 clinicians, and the data were analysed using thematic analysis. Throat swabs were analysed using multiplex polymerase chain reaction. Results: A total of 432 children were randomised (antibiotics, n = 221; placebo, n = 211). The primary analysis imputed missing data for 115 children. The duration of moderately bad symptoms was similar in the antibiotic and placebo groups overall (median of 5 and 6 days, respectively; hazard ratio 1.13, 95% confidence interval 0.90 to 1.42), with similar results for subgroups, and when including antibiotic prescription data from the 326 children in the observational study. Reconsultations for new or worsening symptoms (29.7% and 38.2%, respectively; risk ratio 0.80, 95% confidence interval 0.58 to 1.05), illness progression requiring hospital assessment or admission (2.4% vs. 2.0%) and side effects (38% vs. 34%) were similar in the two groups. Complete-case (n = 317) and per-protocol (n = 185) analyses were similar, and the presence of bacteria did not mediate antibiotic effectiveness. NHS costs per child were slightly higher (antibiotics, £29; placebo, £26), with no difference in non-NHS costs (antibiotics, £33; placebo, £33). A model predicting complications (with seven variables: baseline severity, difference in respiratory rate from normal for age, duration of prior illness, oxygen saturation, sputum/rattly chest, passing urine less often, and diarrhoea) had good discrimination (bootstrapped area under the receiver operator curve 0.83) and calibration. Parents found it difficult to interpret symptoms and signs, used the sounds of the child's cough to judge the severity of illness, and commonly consulted to receive a clinical examination and reassurance. Parents acknowledged that antibiotics should be used only when 'necessary', and clinicians noted a reduction in parents' expectations for antibiotics. Limitations: The study was underpowered to detect small benefits in key subgroups. Conclusion: Amoxicillin for uncomplicated lower respiratory tract infections in children is unlikely to be clinically effective or to reduce health or societal costs. Parents need better access to information, as well as clear communication about the self-management of their child's illness and safety-netting. Future work: The data can be incorporated in the Cochrane review and individual patient data meta-analysis. Trial registration: This trial is registered as ISRCTN79914298. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 9. See the NIHR Journals Library website for further project information.

Children are commonly prescribed antibiotics for chest infections, but such infections are becoming resistant to antibiotics, and it is not clear if antibiotics work in treating them. A total of 432 children who saw their general practitioner with a chest infection were given either an antibiotic (amoxicillin) or a placebo (no antibiotic) for 7 days. Symptom diaries documented the infection's duration and its side effects. Children not in the placebo study were able to participate in another study that documented the same outcomes (an 'observational study'). We interviewed parents, doctors and nurses about their observations and concerns. Our patient and public involvement and engagement work with parents indicated that a 3-day symptom reduction was required to justify giving antibiotics. After seeing the doctor, parents whose children received antibiotics rated infective symptoms as moderately bad or worse for 5 days, and parents whose children received the placebo rated these for 6 days. Side effects and complications were similar in the two groups. Findings were similar when including the results of the observational study, and for children in whose chest the doctor could hear wheeze or rattles; who had fever; who were rated by the doctor as more unwell, who were short of breath, or who had had bacteria detected in the throat. The costs to the NHS per child were similar (antibiotics, £29; placebo, £26), and the wider costs to society were the same (antibiotics, £33; placebo, £33). Parents found it difficult to interpret their child's symptoms, and commonly used the sound of the cough to judge severity. Parents commonly consulted to receive an examination and reassurance, and accepted that antibiotics should be used only when 'necessary'. Clinicians noted a reduction in parents' expectations for antibiotics. Amoxicillin for chest infections in children is unlikely to be effective. General practitioners should support parents to self-manage at home and give clear communication about when and how to seek medical help if they continue to be concerned.

Neuraminidase inhibitors for preventing and treating influenza in children.

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. 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.

Neuraminidase inhibitors for preventing and treating influenza in children (published trials only).

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.

Clinical symptoms and signs for the diagnosis of Mycoplasma pneumoniae in children and adolescents with community-acquired pneumonia.

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.

Symptomatic treatment of the cough in whooping cough.

BACKGROUND: The worldwide incidence of whooping cough (pertussis) has been estimated at 48.5 million cases and nearly 295,000 deaths per year. In low-income countries, the case-fatality rate among infants may be as high as 4%. 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, beta 2-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 searches of the Cochrane Central Register of Controlled Trials (CENTRAL Issue 2, 2012), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, the Database of Abstracts of Reviews of Effects (DARE Issue 2, 2012) accessed from The Cochrane Library, MEDLINE (1950 to January 2012), EMBASE (1980 to January 2012), AMED (1985 to January 2012), CINAHL (1980 to January 2012) and LILACS (January 2012). 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 search in 2012. 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: Ten trials were included of varying sample sizes (N = 9 to 135) from high-income countries. Study quality was generally poor. 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. One study on pertussis immunoglobulin reported a possible mean reduction of -3.1 whoops per 24 hours (95% CI -6.2 to 0.02) but no change in hospital stay (MD -0.7 days; 95% CI -3.8 to 2.4). Dexamethasone did not show a clear decrease in length of hospital stay (MD -3.5 days; 95% CI -15.3 to 8.4) and salbutamol showed no change in coughing paroxysms per 24 hours (MD -0.2; 95% CI -4.1 to 3.7). Only one trial comparing pertussis immunoglobulin versus placebo 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.

Prioritizing areas for quality marker development in children in UK general practice: extending the use of the nominal group technique.

BACKGROUND: There is a deficiency in the ability to measure the quality of care of children in primary care and there is no professional consensus in UK general practice regarding which quality markers should be used. OBJECTIVES: To prioritize clinical areas on which to focus quality marker development in paediatric primary care and to describe the challenges in generating professional consensus. METHODS: We convened an expert panel of GPs with a special interest in child health and using the nominal group technique (NGT), a well-established structured, multistep facilitated group meeting technique, we generated consensus around the key clinical areas to focus quality marker development. RESULTS: Twelve GPs participated in the expert panel. The eight items agreed by panellists as most important were early recognition of serious illness, whole practice involvement in safeguarding, health promotion, mental health, evidence-based management of common conditions, child and carer friendliness and safe and cost-effective prescribing. Panel members struggled to balance the broad clinical areas while attempting to focus on specific areas that are important. The main challenges included managing panel uncertainty, effective organization, presentation of items for review and group inclination to 'include everything'. CONCLUSIONS: This is the first consensus study of UK GPs to identify key areas to target quality marker development in children. By using the NGT, we have highlighted front-line health care professionals' priorities to improve the quality of care of children and identified the benefits and challenges of developing consensus in a broad topic area.