Royal Belfast Hospital for Sick Children

BACKGROUND: Children born by Caesarean section have modified intestinal bacterial colonization and consequently may have an increased risk of developing asthma under the hygiene hypothesis. The results of previous studies that have investigated the association between Caesarean section and asthma have been conflicting. OBJECTIVE: To review published literature and perform a meta-analysis summarizing the evidence in support of an association between children born by Caesarean section and asthma. METHODS: MEDLINE, Web Science, Google Scholar and PubMed were searched to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were calculated for each study from the reported prevalence of asthma in children born by Caesarean section and in control children. Meta-analysis was then used to derive a combined OR and test for heterogeneity in the findings between studies. RESULTS: Twenty-three studies were identified. The overall meta-analysis revealed an increase in the risk of asthma in children delivered by Caesarean section (OR=1.22, 95% CI 1.14, 1.29). However, in this analysis, there was evidence of heterogeneity (I(2)=46%) that was statistically significant (P<0.001). Restricting the analysis to childhood studies, this heterogeneity was markedly decreased (I(2)=32%) and no longer attained statistical significance (P=0.08). In these studies, there was also evidence of an increase (P<0.001) in the risk of asthma after Caesarean section (OR=1.20, 95% CI 1.14, 12.6). CONCLUSION: In this meta-analysis, we found a 20% increase in the subsequent risk of asthma in children who had been delivered by Caesarean section.

Aicardi-Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi-Goutières syndrome-related genes. Our findings also make it clear that a window of therapeutic opportunity exists relevant to the majority of affected patients and indicate that the assessment of type I interferon activity might serve as a useful biomarker in future clinical trials.

BACKGROUND: Hypophosphatasia results from mutations in the gene for the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). Inorganic pyrophosphate accumulates extracellularly, leading to rickets or osteomalacia. Severely affected babies often die from respiratory insufficiency due to progressive chest deformity or have persistent bone disease. There is no approved medical therapy. ENB-0040 is a bone-targeted, recombinant human TNSALP that prevents the manifestations of hypophosphatasia in Tnsalp knockout mice. METHODS: We enrolled infants and young children with life-threatening or debilitating perinatal or infantile hypophosphatasia in a multinational, open-label study of treatment with ENB-0040. The primary objective was the healing of rickets, as assessed by means of radiographic scales. Motor and cognitive development, respiratory function, and safety were evaluated, as well as the pharmacokinetics and pharmacodynamics of ENB-0040. RESULTS: Of the 11 patients recruited, 10 completed 6 months of therapy; 9 completed 1 year. Healing of rickets at 6 months in 9 patients was accompanied by improvement in developmental milestones and pulmonary function. Elevated plasma levels of the TNSALP substrates inorganic pyrophosphate and pyridoxal 5'-phosphate diminished. Increases in serum parathyroid hormone accompanied skeletal healing, often necessitating dietary calcium supplementation. There was no evidence of hypocalcemia, ectopic calcification, or definite drug-related serious adverse events. Low titers of anti-ENB-0040 antibodies developed in four patients, with no evident clinical, biochemical, or autoimmune abnormalities at 48 weeks of treatment. CONCLUSIONS: ENB-0040, an enzyme-replacement therapy, was associated with improved findings on skeletal radiographs and improved pulmonary and physical function in infants and young children with life-threatening hypophosphatasia. (Funded by Enobia Pharma and Shriners Hospitals for Children; ClinicalTrials.gov number, NCT00744042.).

<b>OBJECTIVE:</b> To determine concordance rate between functional MRI (fMRI) and Wada test for language lateralization in our cohort of patients with medically intractable epilepsy. <b>BACKGROUND:</b> Preoperative fMRI is a non-invasive test that has been used increasingly in the epilepsy surgery centers to lateralize language. However, concordance rate between fMRI and Wada test has been variable in different studies. We report our local experience. <b>DESIGN/METHODS:</b> Patients with intractable focal epilepsy were studied for language lateralization using fMRI and Wada testing between 2007 and 2014. Three language paradigm tasks were used for fMRI studies: verb generation, sentence completion and naming. fMRI laterality indices were defined as a ratio (L-R)/(L+R) between the number of activated voxels in the left and right ROIs for Brodmann areas 44+45+46+8+9 (Anterior Language Area, ALA) and 22+39+40 (Posterior Language Area, PLA). fMRI and Wada results were divided into the right, left or bilateral hemispheric language dominance. <b>RESULTS:</b> 28 patients (15 men) were studied. Mean age at seizure onset was 19.3±14.57 years, and the mean age at fMRI was 34.8±12.48 years. 17 patients had left temporal epilepsy (TLE), 6 right TLE, 3 bilateral TLE, 1 left frontal and 1 multifocal epilepsy. The concordance rate between Wada and fMRI tests for the ALA and PLA was 68.2[percnt] and 52.2[percnt] for sentence completion; 56[percnt] and 52[percnt] for verb generation and 25[percnt] and 35[percnt] for naming paradigm, respectively. The concordance rate did not improve by combining the activation results of the 3 fMRI paradigms. Bilateral representation in Wada test or fMRI accounted for 68[percnt] of the discordant cases. <b>CONCLUSIONS:</b><b>S</b>entence completion and verb generation fMRI paradigms showed greater concordance with Wada test than naming paradigm. The higher discordance between the Wada test and fMRI was related to bilateral results suggestive of less stringent thresholds used for either test. <b>Disclosure:</b> Dr. Massot-Tarrus has nothing to disclose. Dr. Mousavi has nothing to disclose. Dr. Bihari has nothing to disclose. Dr. Hayman-Abello has nothing to disclose. Dr. Hayman-Abello has nothing to disclose. Dr. Mirsattari has nothing to disclose.

The number of prescription opioid overdose deaths has increased dramatically in recent years and many prescribers are unsure how to balance treatment of pain with secondary prevention. Guidelines recommend low-severity injury patients not receive opioids early in the course of their care, but evidence supporting this guideline is limited. Data from 123 096 workers’ compensation claims with back and shoulder injuries were analysed to evaluate this guideline. Back and shoulder injury claimants with early opioid use (≤1 month after injury) had 33% lower (95% CI 24% to 41% lower) odds and 29% higher (95% CI 6% to 58% higher) odds, respectively, of long-term opioid use (&gt;3 months) than claimants with late opioid use, after adjusting for key covariates. Stratified analyses indicate that early opioid use does not appear to increase the risk of long-term use except in cases where no diagnosis or only the diagnosis of unspecified shoulder pain is given prior to prescription.

OBJECTIVE: Our objective was to determine whether adjustments related to patient age are made in the scanning parameters that are determinants of radiation dose for helical CT of pediatric patients. SUBJECTS AND METHODS: This prospective investigation included all body (chest and abdomen) helical CT examinations (n = 58) of neonates, infants, and children (n = 32) referred from outside institutions for whom radiologic consultation was requested. Information recorded included tube current, kilovoltage, collimation, and pitch. Examinations were arbitrarily grouped on the basis of the individual's age: group A, 0-4 years; group B, 5-8 years; group C, 9-12 years; and group D, 13-16 years old. RESULTS: Thirty-one percent (18/58) of the CT examinations were of the chest and 69% (40/58) were of the abdomen. Sixteen percent (9/58) of the CT examinations were combined chest and abdomen. In 22% (2/9) of these combined examinations, tube current was adjusted between the chest and abdomen CT; in one (11%) of these examinations, the tube current was higher for the chest than for the abdomen portion of the CT examination. The mean tube current setting for chest was 213 mA and was 206 mA for the abdomen, with no evident adjustment in tube current based on the age of the patient. Fifty-six percent of the examinations of neonates, infants, or children 8 years old or younger were performed at a collimation of greater than 5 mm and 53% of these examinations were performed using a pitch of 1.0. CONCLUSION: Pediatric helical CT parameters are not adjusted on the basis of the examination type or the age of the child. In particular, these results suggest that pediatric patients may be exposed to an unnecessarily high radiation dose during body CT.

Key Points In clinical practice, the level of arterial oxygenation can be measured either directly by blood gas sampling to measure partial pressure ( P aO 2 ) and percentage saturation ( S aO 2 ) or indirectly by pulse oximetry ( S pO 2 ). This review addresses the strengths and weaknesses of each of these tests and gives advice on their clinical use. The haemoglobin–oxygen dissociation curve describing the relationship between oxygen partial pressure and saturation can be modelled mathematically and routinely obtained clinical data support the accuracy of a historical equation used to describe this relationship. Educational Aims To understand how oxygen is delivered to the tissues. To understand the relationships between oxygen saturation, partial pressure, content and tissue delivery. The clinical relevance of the haemoglobin–oxygen dissociation curve will be reviewed and we will show how a mathematical model of the curve, derived in the 1960s from limited laboratory data, accurately describes the relationship between oxygen saturation and partial pressure in a large number of routinely obtained clinical samples. To understand the role of pulse oximetry in clinical practice. To understand the differences between arterial, capillary and venous blood gas samples and the role of their measurement in clinical practice. The delivery of oxygen by arterial blood to the tissues of the body has a number of critical determinants including blood oxygen concentration (content), saturation ( S O 2 ) and partial pressure, haemoglobin concentration and cardiac output, including its distribution. The haemoglobin–oxygen dissociation curve, a graphical representation of the relationship between oxygen satur­ation and oxygen partial pressure helps us to understand some of the principles underpinning this process. Historically this curve was derived from very limited data based on blood samples from small numbers of healthy subjects which were manipulated in vitro and ultimately determined by equations such as those described by Severinghaus in 1979. In a study of 3524 clinical specimens, we found that this equation estimated the S O 2 in blood from patients with normal pH and S O 2 &gt;70% with remarkable accuracy and, to our knowledge, this is the first large-scale validation of this equation using clinical samples. Oxygen saturation by pulse oximetry ( S pO 2 ) is nowadays the standard clinical method for assessing arterial oxygen saturation, providing a convenient, pain-free means of continuously assessing oxygenation, provided the interpreting clinician is aware of important limitations. The use of pulse oximetry reduces the need for arterial blood gas analysis ( S aO 2 ) as many patients who are not at risk of hypercapnic respiratory failure or metabolic acidosis and have acceptable S pO 2 do not necessarily require blood gas analysis. While arterial sampling remains the gold-standard method of assessing ventilation and oxygenation, in those patients in whom blood gas analysis is indicated, arterialised capillary samples also have a valuable role in patient care. The clinical role of venous blood gases however remains less well defined.

SUMMARY The role of intramuscular botulinum toxin A in the treatment of 26 children with cerebral palsy was evaluated. The indication for injection was the presence of a dynamic contracture of lower‐limb muscles interfering with positioning or walking. Spastic target muscles were identified by clinical examination and, in ambulant children, by gait analysis. Between 50 and 320 units of botulinum toxin were injected into each muscle group to a total dose of 100 to 400 units per child. The effects of injection were monitored by repeated clinical examination and gait analysis. There were no clinically detectable systemic side‐effects, and all but one patient had a reduction in tone, which occurred within three days and persisted for two to four months. There were significant improvements in ambulatory status and in sagittal‐plane kinematics. In some cases these gains persisted after the tone‐reducing effects of the toxin had worn off. RÉSUMÉ La toxine boiulinique dans le iraiiemenl de ľIMC au niveau des membres inférieurs Ľaction dc la toxine botulinique A en intramusculaire a étéévaluée chez 26 enfants IMC. Ľindication de ľinjection était la presence de contractions dynamiques des muscles du membre inférieur perturbant la station‐locomotion. Les cibles musculaires spastiques furent identifiées par ľexamen clinique et par ľanalyse de la démarche chez les enfants marchant. Entre 50 et 320 unités de toxine botulinique ont été injectées dans chaque groupe musculaire avec une dose totale de 100 a 400 unités par enfant. Les effets de ľinjection ont été contrôlés par des examens cliniques répétés et une analyse de la demarche. II n'a été découvert cliniquement aucun effet secondaire, et chez tous les patients sauf un, il a été observe une diminution du tonus, survenant au bout de trois jours et durant de deux à quatre mois. II fut noté des améliorations significatives dans ľallure de la démarche et dans la cinematique du plan sagittal. Dans quelques cas, les améliorations ont persiste alors même que les effets de réduction de tonus de la toxine avaient disparu. ZUSAMMENFASSUNG Botulinum Toxin zur Behandlung der unteren Extremitát bei Cerebralparese Bei 26 Kindern mit Cerebralparese wurde die Wirkung von intramuskulär injiziertem Botulinum Toxin A untersucht. Die Indikation fúr die Injektion war eine dynamische Kontraktur der Beinmuskeln, wodurch Lagerung oder Laufen beeinträchtigt waren. Die spastischen Zielmuskeln wurden durch klinische Untersuchungen und bei gehfähigen Patienten durch Ganganalysen identifiziert. In jede Muskelgruppe wurden 50 bis 320 E Botulinum Toxin injiziert, bis zu einer Gesamtdosis von 100 bis 400 E pro Kind. Die Wirkung der Injektionen wurde durch wiederholte klinische Untersuchungen und Ganganalysen überwacht. Es fanden sich keine klinisch manifesten Nebenwirkungen und bei alien Patienten, außer einem, konnte eine Tonusverminderung festgestellt werden, die innerhalß von drei Tagen auftrat und zwei bis vier Monate anhielt. Es fanden sich signifikante Besserungen der Gehfähigkeit und der sagittalen planen Kinematik. Bei einigen Patienten hielten diese Besserungen weiter an, nachdem die Tonus reduzierende Wirkung des Toxins abgeklungen war. RESUMEN Toxina botulínica en el manejo de la extremidad inferior en la parálisis infantile Se evaluó el papel de la toxina botulinica A por via intramuscular en 26 niños con parálisis cerebral. La indicación para la inyección era la presencia de una contractura dinámica de los músculos de la extremidad inferior que interferia con la postura y la marcha. Los músculos espásticos implicados fueron escogidos por examen clinico y, en niños que andaban, por análisis de la marcha. En cada grupo muscular se inyectaron entre 50 y 320 unidades de toxina botulinica con una dosis total de 100 a 400 unidades por niño. El efecto de la inyección fue monitorizado por exámenes clinicos repetidos y análisis de la marcha. No hubo ningun efecto secundario detectable clinicamente, todos los pacicntes, excepto uno, tuvierón una reduction del tono muscular que apareció en el curso de tres dias y persistió durante dos a cuatro meses. Hubo una mejoria significativa en la marcha y en la cinética en el plano sagital. En algunos casos estas ganancias persistieron después de que se agotara la actión reductora del tono de la toxina.

Cystathionine beta-synthase (CBS) deficiency is a rare inherited disorder in the methionine catabolic pathway, in which the impaired synthesis of cystathionine leads to accumulation of homocysteine. Patients can present to many different specialists and diagnosis is often delayed. Severely affected patients usually present in childhood with ectopia lentis, learning difficulties and skeletal abnormalities. These patients generally require treatment with a low-methionine diet and/or betaine. In contrast, mildly affected patients are likely to present as adults with thromboembolism and to respond to treatment with pyridoxine. In this article, we present recommendations for the diagnosis and management of CBS deficiency, based on a systematic review of the literature. Unfortunately, the quality of the evidence is poor, as it often is for rare diseases. We strongly recommend measuring the plasma total homocysteine concentrations in any patient whose clinical features suggest the diagnosis. Our recommendations may help to standardise testing for pyridoxine responsiveness. Current evidence suggests that patients are unlikely to develop complications if the plasma total homocysteine concentration is maintained below 120 μmol/L. Nevertheless, we recommend keeping the concentration below 100 μmol/L because levels fluctuate and the complications associated with high levels are so serious.

In a randomised, double-blind study, the effects of intramuscular injection of botulinum toxin type A (BtA) into the upper limb were compared with those of normal saline solution in 14 patients with cerebral palsy; their mean age was 9 years. Range of movement and function were assessed before injection and at 2 and 12 weeks after injection. BtA injection significantly increased maximum active elbow and thumb extension and significantly reduced tone at wrist and elbow. The hand grasp-and-release score improved, representing a modest functional change, but fine motor function, assessed by the ability to pick up coins, did not improve and in some cases deteriorated temporarily. The most notable subjective change was the cosmetic benefit of reduced involuntary elbow flexion. The tone-reducing effect of BtA was clinically detectable in comparison with the placebo and patients and parents perceived the change as beneficial. The median of changes in the treatment group was small but the range was large, suggesting that BtA can be useful in selected patients.

BACKGROUND: It seems plausible that children with atopy and persistent asthma symptoms will, like their adult counterparts, have chronic airways inflammation. However, many young children with no other atopic features have episodic wheezing that is triggered solely by viral respiratory infections. Little is known as to whether airways inflammation occurs in these two asthma patterns during relatively asymptomatic periods. METHODS: Using a non-bronchoscopic bronchoalveolar lavage (BAL) procedure on children presenting for an elective surgical procedure, this study has investigated the cellular constituents of BAL fluid in children with a history of atopic asthma (AA) non-asthmatic atopic children (NAA) or viral associated wheeze (VAW). RESULTS: A total of 95 children was studied: 52 with atopic asthma (8.0 years, range 1.1-15.3, 36 male), 23 with non-asthmatic atopy (median age 8.3 years, range 1.7-13.6, 11 male) and 20 with VAW (3.1 years, range 1.0-8.2, 13 male). No complications were observed during the lavage procedure and no adverse events were noted post-operatively. Total lavage fluid recovered was similar in all groups and the total cell numbers were higher in the VAW group. Eosinophil (P < or = 0.005) and mast cell (P < or = 0.05) numbers were significantly elevated in the group with atopic asthma. CONCLUSIONS: During relatively asymptomatic periods there is on-going airways inflammation, as demonstrated by eosinophil and mast cell recruitment, in children with asthma and atopy but not in children with viral associated wheeze or atopy alone. This strongly suggests that there are different underlying pathophysiological mechanisms in these two groups of children who wheeze.

<b>Background:</b> We have previously found that both obstructive sleep apnea (OSA) and central sleep apnea (CSA) have high prevalence in hospitalized patients with heart failure with reduced ejection fraction (HFrEF) and that SDB predicted post discharge mortality and readmissions. The role of SDB in post discharge outcomes in patients with HFpEF remains less well understood. <b>Methods:</b> We used an established inception prospective cohort of hospitalized heart failure patients who had inpatient testing for SDB (The OSU-Sleep Heart Program) to identify a subgroup of HFpEF (EF &lt; 45%) who underwent sleep testing. Patients who underwent sleep studies had their readmissions and vital status tracked post discharge. <b>Results:</b> Between 2009 and 2013, 1569 patients admitted for heart failure underwent sleep studies during hospitalization. Of those, 400 had HFpEF. 69 (17.3%) patients had CSA, and 204 (51%) had OSA. The remainder had no SDB (apnea hypopnea index &lt;15) (Table-1) The rate ratio for 6 month readmissions was 3.22 (95% CI 1.66, 6.25) (p&lt;0.001) in CSA patients compared to no SDB. This rate ratio is adjusted for age, sex, diabetes, chronic kidney disease and coronary artery disease. The adjusted rate ratio for 6 month readmissions was 2.08 (95% CI 1.23, 3.5) (p=0.01) in OSA patients compared no SDB (Table-2). <b>Conclusion:</b> In hospitalized HFpEF patients, OSA was more prevalent that CSA. Similar to patients with HFrEF, both OSA and CSA were independent predictors of readmissions.

Pathological findings are described in four cases of a new aminoaciduria in which homocystine is excreted in the urine. All the patients were mentally retarded children. Three of them presented diagnostic features of Marfan's syndrome. Necropsy on one case and biopsy findings in the others are described. Fatty change occurs in the liver. The most striking lesions are vascular. Metachromatic medial degeneration of the aorta and of the elastic arteries in the necropsied case are considered in relation to Marfan's syndrome. Other changes, particularly thrombosis which is prevalent in homocystinuria, suggest the possibility of a platelet defect. The findings are discussed in respect of an upset in the metabolism of sulphur-containing amino-acids and with particular reference to Marfan's syndrome.

Respiratory syncytial virus (RSV) is the major viral cause of severe pulmonary disease in young infants worldwide. However, the mechanisms by which RSV causes disease in humans remain poorly understood. To help bridge this gap, we developed an ex vivo/in vitro model of RSV infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs), the primary targets of RSV infection in vivo. Our RSV/WD-PBEC model demonstrated remarkable similarities to hallmarks of RSV infection in infant lungs. These hallmarks included restriction of infection to noncontiguous or small clumps of apical ciliated and occasional nonciliated epithelial cells, apoptosis and sloughing of apical epithelial cells, occasional syncytium formation, goblet cell hyperplasia/metaplasia, and mucus hypersecretion. RSV was shed exclusively from the apical surface at titers consistent with those in airway aspirates from hospitalized infants. Furthermore, secretion of proinflammatory chemokines such as CXCL10, CCL5, IL-6, and CXCL8 reflected those chemokines present in airway aspirates. Interestingly, a recent RSV clinical isolate induced more cytopathogenesis than the prototypic A2 strain. Our findings indicate that this RSV/WD-PBEC model provides an authentic surrogate for RSV infection of airway epithelium in vivo. As such, this model may provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines or therapeutics.

OBJECTIVE: To establish the relative risks of in utero exposure to lamotrigine (LTG), sodium valproate (NaV) and carbamazepine (CBZ) monotherapy for neurodevelopment. DESIGN: Observational cohort study. PATIENTS AND METHODS: The study group consisted of children in Northern Ireland aged 9-60 months born to mothers who had enrolled with the UK Epilepsy and Pregnancy Register. The control group consisted of children identified from the Child Health System database across Northern Ireland. Data were gathered on covariates recognised as influencing child development. MAIN OUTCOME MEASURES: Neurodevelopment assessed using either the Bayley Scales of Infant Development or the Griffiths Mental Development Scales. RESULTS: 210 children underwent assessment by a single researcher blinded to antiepileptic drug exposure. 23 (39.6%) children exposed in utero to NaV, 10 (20.4%) exposed to CBZ and one (2.9%) exposed to LTG had evidence of mild or significant developmental delay, compared to two (4.5%) children in the control group. Multivariable analysis demonstrated that in utero exposure to NaV (OR 26.1, 95% CI 4.9 to 139; p<0.001) and to CBZ (OR 7.7, 95% CI 1.4 to 43.1; p<0.01) but not to LTG had a significant detrimental effect on neurodevelopment. CONCLUSION: In utero exposure to LTG did not have the detrimental effect on child development that was seen with NaV and with CBZ.

Increasing concern has recently been expressed in the literature that the referring doctor's knowledge of radiation doses incurred during radiological procedures is inadequate. Such information may be particularly relevant when the expansion of imaging technology is considered. To assess this, a survey was conducted of the awareness of radiation dose and risk among health professionals in Northern Ireland. A questionnaire was circulated to 300 consultants and 200 junior doctors selected randomly from a range of specialties. Participants were asked about the radiation dose from a chest radiograph, the annual dose from background radiation, and to estimate the radiation dose and cancer risk from several common radiological procedures. In total, 153 questionnaires were returned. A mean score of 7.1 out of 18 was achieved (39%). 26% of doctors achieved a score of 50% or more, and 20% of respondents knew the effective dose of a chest radiograph. 52 doctors had received formal training about ionizing radiation, and these participants scored more highly than those with no previous training in this area (p = 0.003). Our survey confirmed that clinician awareness of radiation doses imparted during common radiological procedures, and the consequent risk to the individual patient, is poor. It identified that training does increase awareness about radiation dose. There is a need to educate clinicians about (i) ionizing radiation relevant to medical imaging, given their legal responsibility as referrers under the Ionizing Radiation (Medical Exposure) regulations in the UK, and (ii) their clinical role to provide accurate information to their patients.

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.

BACKGROUND: Studies based on molecular testing of oral/nasal swabs underestimate SARS-CoV-2 infection due to issues with test sensitivity, test timing and selection bias. The objective of this study was to report the presence of SARS-CoV-2 antibodies, consistent with previous infection. DESIGN: This multicentre observational cohort study, conducted between 16 April to 3 July 2020 at 5 UK sites, recruited children of healthcare workers, aged 2-15 years. Participants provided blood samples for SARS-CoV-2 antibody testing and data were gathered regarding unwell contacts and symptoms. RESULTS: 1007 participants were enrolled, and 992 were included in the final analysis. The median age of participants was 10·1 years. There were 68 (6.9%) participants with positive SARS-CoV-2 antibody tests indicative of previous SARS-CoV-2 infection. Of these, 34/68 (50%) reported no symptoms prior to testing. The presence of antibodies and the mean antibody titre was not influenced by age. Following multivariable analysis four independent variables were identified as significantly associated with SARS-CoV-2 seropositivity: known infected household contact OR=10.9 (95% CI 6.1 to 19.6); fatigue OR=16.8 (95% CI 5.5 to 51.9); gastrointestinal symptoms OR=6.6 (95% CI 3.0 to 13.8); and changes in sense of smell or taste OR=10.0 (95% CI 2.4 to 11.4). DISCUSSION: Children demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. Fatigue, gastrointestinal symptoms and changes in sense of smell or taste were the symptoms most strongly associated with SARS-CoV-2 antibody positivity. TRIAL REGISTRATION NUMBER: NCT0434740.

SUMMARY The hereditary spastic mouse was studied as a model of cerebral palsy in childhood to test the hypothesis that intramuscular botulinum toxin A would prevent the development of calf‐muscle contractures. A prospective randomised controlled trial of calf injection with botulinum A compared with injection of normal saline was performed on juvenile mice. At maturity, the calf muscles of the spastic mice were 16 per cent shorter than those of their normal siblings. The calf muscles of spastic mice injected with botulinum toxin A grew to within 2 per cent of normal length. This difference in mature muscle length was highly significant. RÉSUMÉ La toxine botulinique A dans la prévention des contractures chez la souris avec spasticité héréditaire La souris avec spasticité héréditaire a été utilisée comme modèle ďIMC de ľenfance pour évaluer ľhypothèse selon laquelle la toxine musculaire A en intramusculaire préviendrait le développement de rétractions des ischio‐jambiers. Un essai prospectif contrôlé et aléatoire ďinjection dans la région postérieure de la cuisse, dc toxine botulinique A ou de sérum salé isotonique a été effectué chez de jeunes souris spastiques. A maturité, les ischio‐jambiers des souris spastiques non traitées étaient de 16 pour cent plus courts que ches les contrôles de fratrie normaux. Les ischio‐jambiers des souris spastiques ayant bénéficié de ľinjection de toxine botulinique étaient dans les deux pour cent de la croissance normale. Cette différence sur la longueur des muscles à maturité est hautement significative. ZUSAMMENFASSUNG Botulinum Toxin A verhindert die Entwicklung von Kontrakluren bei der heriditáren Spastik der Maus Die heriditäre Spastik der Maus wurde als Modell für die Cerebralparese im Kindesalter untersucht. urn die Hypothese zu prüfen, daß intramuskuláre lnjektionen von Botulinum Toxin A die Entwicklung von Kontrakturen der Wadenmuskulatur verhindert. Es wurde ein propektiver randomisierter kontrollierter Versuch von lnjektionen mit Botulinum Toxin A und vergleichsweise mit Kochsalzlösung in die Wadenmuskulatur juveniler Mause durchgefiihrt. Voll entwickelt waren die Wadenmuskeln der spasiischen Mäuse 16 Prozent kürzer als die ihrer gesunden Geschwister. Die Wadenmuskeln der spastischen Mause, denen Botulinum Toxin A injiziert worden war, wuchsen bis auf 2 Prozent der normalen Länge. Dieser Längenunterschied des reifen Muskels war hochsignifikant. RESUMEN La loxina Botulinica A impide el desarrollo de contracturas en el raión con espasticidad hereditaria Se estudio el ratón con espasticidad hereditaria como modelo de la parálisis cerebral del niño para comprobar la hipótesis de que la toxina boiulinica A intramuscular podia prevenir el desarrollo de contracturas en los músculos de la pantorrila. Se realizó en ratones jovenes un ensayo prospectivo, randomizado y controlado, con inyección en la pantorrila de botulina A y se comparó con la inyección de una solución salina. Al llegar a la madurez, los músculos de la pantorrila de los ratones espasticos eran un 16 por ciento más cartos que los de sus hermanos normales. Los músculos de la pantorrila de los ratones espasticos inyectados con toxina boiulinica A crecieron dentro de un 2 por ciento de su longitud normal. Esta diferencia en la longitud del músculo maduro era altamente significativa.