Angela Wade

Investigation of risk factors in children with arterial ischemic stroke

We present data on the known risk factors encountered in children presenting with a first arterial ischemic stroke to a single tertiary center over 22 years. Two hundred twelve patients (54% male; median age, 5 years) were identified. One hundred fifteen (54%) were previously healthy. Cerebral arterial imaging was undertaken in 185 patients (87%) and was abnormal in 79%. Of 104 previously healthy patients investigated with echocardiography, only 8 had abnormal studies. Genetic or acquired conditions causing thrombophilia were rare. Forty percent of patients were anemic, and 21% either had elevated total plasma homocysteine or were homozygous for the t‐MTHFR mutation. Trauma and previous varicella zoster infection were significantly more common in the previously healthy group. There was a significant association between cerebral arterial abnormalities and systolic blood pressure greater than 90th percentile and a trend for an association with varicella within the previous year. Clinical history and examination usually identify underlying risk factors and precipitating triggers for arterial ischemic stroke in childhood. Cerebral arterial imaging is usually abnormal, but echocardiography and prothrombotic screening are commonly negative. Ann Neurol 2003

Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study

BACKGROUND Convulsive status epilepticus is the most common childhood medical neurological emergency, and is associated with significant morbidity and mortality. Most data for this disorder are from mainly adult populations and might not be relevant to childhood. Thus we undertook the North London Status Epilepticus in Childhood Surveillance Study (NLSTEPSS): a prospective, population-based study of convulsive status epilepticus in childhood, to obtain a uniquely paediatric perspective. METHODS Clinical and demographic data for episodes of childhood convulsive status epilepticus that took place in north London were obtained through a clinical network that covered the target population. We obtained these data from anonymised copies of a standardised admission proforma; accident and emergency, nursing, ambulance, and intensive-care unit notes; and interviews with parents, medical, nursing, and paramedic staff. We investigated ascertainment using capture-recapture modelling. FINDINGS Of 226 children enrolled, 176 had a first ever episode of convulsive status epilepticus. We estimated that ascertainment was between 62% and 84%. The ascertainment-adjusted incidence was between 17 and 23 episodes per 100,000 per year. 98 (56%, 95% CI 48-63) children were neurologically healthy before their first ever episode and 56 (57%, 47-66) of those children had a prolonged febrile seizure. 11 (12%, 6-18) of children with first ever febrile convulsive status epilepticus had acute bacterial meningitis. Conservative estimation of 1-year recurrence of convulsive status epilepticus was 16% (10-24%). Case fatality was 3% (2-7%). INTERPRETATION Convulsive status epilepticus in childhood is more common, has a different range of causes, and a lower risk of death than that in adults. These paediatric data will help inform management of convulsive status epilepticus and appropriate allocation of resources to reduce the effects of this disorder in childhood.

Clinical and Radiological Recurrence After Childhood Arterial Ischemic Stroke

Background— Data on rates and risk factors for clinical and radiological recurrence of childhood arterial ischemic stroke (AIS) might inform secondary prevention strategies. Methods and Results— Consecutive Great Ormond Street Hospital patients with first AIS were identified retrospectively (1978–1990) and prospectively (1990–2000). Patients underwent repeat neuroimaging at the time of clinical recurrence or, if asymptomatic, at least 1 year after AIS. Cox and logistic regression analyses were used to explore the relationships between risk factors and clinical and radiological recurrence, respectively. A total of 212 patients were identified, of whom 97 had another prior diagnosis. Seventy-nine children had a clinical recurrence (29 strokes, 46 transient ischemic attacks [TIAs], 4 deaths with reinfarction 1 day to 11.5 years (median 267 days) later); after 5 years, 59% (95% confidence interval, 51% to 67%) were recurrence free. Moyamoya on angiography and low birth weight were independently associated with clinical recurrence in the whole group. Genetic thrombophilia was associated with clinical recurrence in previously healthy patients, independent of the presence of moyamoya. Sixty of 179 patients who had repeat neuroimaging had radiological reinfarction, which was clinically silent in 20. Previous TIA, bilateral infarction, prior diagnosis (specifically immunodeficiency), and leukocytosis were independently associated with reinfarction. Previous TIA and leukocytosis were also independently associated with clinically silent reinfarction. Conclusions— Clinical and radiological recurrence are common after childhood AIS. The risk of clinical recurrence is increased in children with moyamoya and, in previously healthy patients, in those with genetic thrombophilia. Preexisting pathology, including immunodeficiency, and persistent leukocytosis are risk factors for radiological recurrence, which suggests a potential role for chronic infection.

Lung function from infancy to the preschool years after clinical diagnosis of cystic fibrosis.

RATIONALE After recent standardization of forced expiratory maneuvers for both infants and preschool children, longitudinal measurements are now possible from birth. OBJECTIVES The aim of this study was to investigate the evolution of lung function during the first 6 years of life after a clinical diagnosis of cystic fibrosis (CF) in infancy in children with CF and in healthy control subjects. METHODS The raised volume technique was used during infancy and incentive spirometry during the preschool years. MEASUREMENTS AND MAIN RESULTS Forty-eight children with CF and 33 healthy control subjects had up to seven (median, 3) measurements. Over these early years, the diagnosis of CF itself accounted for a significant mean reduction of 7.5% (95% confidence interval, 0.9 - 13.6%) in FEV(0.75) and 15.1% (95% confidence interval, 3.6 - 25.3%) in FEF(25-75). Wheeze on auscultation, recent cough, and Pseudomonas aeruginosa (PsA) infection (even if apparently effectively treated) were all independently associated with further reductions in lung function. Premorbid lung function did not predict infection with PsA. CONCLUSIONS This is the first study to describe physiologic measurements from infancy through the preschool years in subjects with CF and healthy control subjects, the understanding of which is critical for future intervention trials. Airflow obstruction in uncomplicated CF persists through the preschool years despite treatment, with PsA acquisition being associated with further deterioration in lung function, even when apparently eradicated. This suggests that new therapies are needed to treat the airflow obstruction of uncomplicated CF, and rigorous strategies to prevent PsA acquisition.

Symptom-pattern phenotype and pulmonary function in preschool wheezers

BACKGROUND Pulmonary function in preschool wheezing phenotypes based on wheeze onset and duration and atopic status has been extensively described but has not been studied in symptom-pattern phenotypes of episodic (viral) and multiple-trigger wheeze. OBJECTIVE We investigated whether multiple-trigger wheezers were more likely to have abnormal pulmonary function and increased fraction of exhaled nitric oxide (FeNO) than episodic (viral) wheezers and whether multiple-breath wash-out was more sensitive at detecting abnormal pulmonary function than specific airways resistance (sR(aw)) in preschool wheezers. METHODS FeNO, multiple-breath wash-out indices (lung clearance index [LCI] and conductive airways ventilation inhomogeneity [S(cond)]) and sR(aw) were measured in healthy children and those with recurrent wheeze aged 4 to 6 years. Subgroup analysis was performed according to current symptom-pattern (multiple-trigger vs episodic [viral]), atopic status (atopic vs nonatopic), and wheeze status (currently symptomatic vs asymptomatic). RESULTS Seventy-two control subjects and 62 wheezers were tested. Multiple-trigger wheezers were associated with an average increase of 11% (95% CI, 7% to 18%; P < .001) in LCI, 211% (95% CI, 70% to 470%; P < .001) in S(cond), and 15% (95% CI, 3% to 28%; P = .01) in sR(aw) compared with episodic (viral) wheezers. Pulmonary function in episodic (viral) wheezers did not differ significantly from control subjects. The presence of current atopy or wheeze was associated with higher FeNO (P = .05) but did not influence pulmonary function significantly. On average, LCI was abnormal in 39% (95% CI, 32% to 45%), S(cond) was abnormal in 68% (95% CI, 61% to 74%), and sR(aw) was abnormal in 26% (95% CI, 16% to 35%) of multiple-trigger wheezers. CONCLUSIONS Multiple-trigger wheeze is associated with pulmonary function abnormalities independent of atopic and current wheeze status. S(cond) is the most sensitive indicator of abnormal pulmonary function in preschool wheezers.

Lung function is abnormal in 3-month-old infants with cystic fibrosis diagnosed by newborn screening

Background Long-term benefits of newborn screening (NBS) for cystic fibrosis (CF) have been established with respect to nutritional status, but effects on pulmonary health remain unclear. Hypothesis With early diagnosis and commencement of standardised treatment, lung function at ∼3 months of age is normal in NBS infants with CF. Methods Lung clearance index (LCI) and functional residual capacity (FRC) using multiple breath washout (MBW), plethysmographic (pleth) FRC and forced expirations from raised lung volumes were measured in 71 infants with CF (participants in the London CF Collaboration) and 54 contemporaneous healthy controls age ∼3 months. Results Compared with controls, and after adjustment for body size and age, LCI, FRCMBW and FRCpleth were significantly higher in infants with CF (mean difference (95% CI): 0.5 (0.1 to 0.9), p=0.02; 0.4 (0.1 to 0.7), p=0.02 and 0.9 (0.4 to 1.3), p<0.001, z-scores, respectively), while forced expiratory volume (FEV0.5) and flows (FEF25–75) were significantly lower (−0.9 (−1.3 to −0.6), p<0.001 and −0.7 (−1.1 to −0.2), p=0.004, z-scores, respectively). 21% (15/70) of infants with CF had an elevated LCI (>1.96 z-scores) and 25% (17/68) an abnormally low FEV0.5 (below −1.96 z-scores). While only eight infants with CF had abnormalities of LCI and FEV0.5, using both techniques identified abnormalities in 35% (24/68). Hyperinflation (FRCpleth >1.96 z-scores) was identified in 18% (10/56) of infants with CF and was significantly correlated with diminished FEF25–75 (r=−0.43, p<0.001) but not with LCI or FEV0.5. Conclusion Despite early diagnosis of CF by NBS and protocol-driven treatment in specialist centres, abnormal lung function, with increased ventilation inhomogeneity and hyperinflation and diminished airway function, is evident in many infants with CF diagnosed through NBS by 3 months of age.

Urban residential fire and flame injuries: a population based study

Background—Fires are a leading cause of death, but non-fatal injuries from residential fires have not been well characterised. Methods—To identify residential fire injuries that resulted in an emergency department visit, hospitalisation, or death, computerised databases from emergency departments, hospitals, ambulance and helicopter services, the fire department, and the health department, and paper records from the local coroner and fire stations were screened in a deprived urban area between June 1996 and May 1997. Result—There were 131 fire related injuries, primarily smoke inhalation (76%), an incidence of 36 (95% confidence interval (CI) 30 to 42)/100 000 person years. Forty one patients (32%) were hospitalised (11 (95% CI 8 to 15)/100 000 person years) and three people (2%) died (0.8 (95% CI 0.2 to 2.4)/100 000 person years). Injury rates were highest in those 0–4 (68 (95% CI 39 to 112)/100 000 person years) and ≥85 years (90 (95% CI 29 to 213)/100 000 person years). Rates did not vary by sex. Leading causes of injury were unintentional house fires (63%), assault (8%), clothing and nightwear ignition (6%), and controlled fires (for example, gas burners) (4%). Cooking (31%) and smokers materials (18%) were leading fire sources. Conclusions—Because of the varied causes of fire and flame injuries, it is likely that diverse interventions, targeted to those at highest risk, that is, the elderly, young children, and the poor, may be required to address this important public health problem.

Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study

Objectives To assess the accuracy of fetal RHD genotyping using cell-free fetal DNA in maternal plasma at different gestational ages. Design A prospective multicentre cohort study. Setting Seven maternity units in England. Participants RhD negative pregnant women who booked for antenatal care before 24 weeks’ gestation. Interventions Women who gave consent for fetal RHD genotyping had blood taken at the time of booking for antenatal care and, when possible, at other routine visits such as for Down’s syndrome screening between 11 and 21 weeks’ gestation, at the anomaly scan at 18-21 weeks, and in the third trimester when blood was taken for the routine antibody check. The results of cord blood analysis, done routinely in RhD negative pregnancies, were also obtained to confirm the fetal RHD genotyping. Main outcome measures The accuracy of fetal RHD genotyping compared with RhD status predicted by cord blood serology. Results Up to four analyses per woman were performed in 2288 women, generating 4913 assessable fetal results. Sensitivity for detection of fetal RHD positivity was 96.85% (94.95% to 98.05%), 99.83% (99.06% to 99.97%), 99.67% (98.17% to 99.94%), 99.82% (98.96% to 99.97%), and 100% (99.59% to 100%) at <11, 11-13, 14-17, 18-23, and >23 completed weeks’ gestation, respectively. Before 11 weeks’ gestation 16/865 (1.85%) babies tested were falsely predicted as RHD negative. Conclusions Mass throughput fetal RHD genotyping is sufficiently accurate for the prediction of RhD type if it is performed from 11 weeks’ gestation. Testing before this time could result in a small but significant number of babies being incorrectly classified as RHD negative. These mothers would not receive anti-RhD immunoglobulin, and there would be a risk of haemolytic disease of the newborn in subsequent pregnancies.

The "Let's Get Alarmed!" initiative: a smoke alarm giveaway programme

Objectives—To reduce fires and fire related injuries by increasing the prevalence of functioning smoke alarms in high risk households. Setting—The programme was delivered in an inner London area with above average material deprivation and below average smoke alarm ownership. The target population included low income and rental households and households with elderly persons or young children. Methods—Forty wards, averaging 4000 households each, were randomised to intervention or control status. Free smoke alarms and fire safety information were distributed in intervention wards by community groups and workers as part of routine activities and by paid workers who visited target neighbourhoods. Recipients provided data on household age distribution and housing tenure. Programme costs were documented from a societal perspective. Data are being collected on smoke alarm ownership and function, and on fires and related injuries and their costs. Results—Community and paid workers distributed 20 050 smoke alarms, potentially sufficient to increase smoke alarm ownership by 50% in intervention wards. Compared with the total study population, recipients included greater proportions of low income and rental households and households including children under 5 years or adults aged 65 and older. Total programme costs were £145 087. Conclusions—It is possible to implement a large scale smoke alarm giveaway programme targeted to high risk households in a densely populated, multicultural, materially deprived community. The programmes effects on the prevalence of installed and functioning alarms and the incidence of fires and fire related injuries, and its cost effectiveness, are being evaluated as a randomised controlled trial.

Prevalence of working smoke alarms in local authority inner city housing: randomised controlled trial

Abstract Objectives: To identify which type of smoke alarm is most likely to remain working in local authority inner city housing, and to identify an alarm tolerated in households with smokers. Design: Randomised controlled trial. Setting:Two local authority housing estates in inner London. Participants: 2145 households. Intervention: Installation of one of five types of smoke alarm (ionisation sensor with a zinc battery; ionisation sensor with a zinc battery and pause button; ionisation sensor with a lithium battery and pause button; optical sensor with a lithium battery; or optical sensor with a zinc battery). Main outcome measure: Percentage of homes with any working alarm and percentage in which the alarm installed for this study was working after 15 months. Results: 54.4% (1166/2145) of all households and 45.9% (465/1012) of households occupied by smokers had a working smoke alarm. Ionisation sensor, lithium battery, and there being a smoker in the household were independently associated with whether an alarm was working (adjusted odds ratios 2.24 (95% confidence interval 1.75 to 2.87), 2.20 (1.77 to 2.75), and 0.62 (0.52 to 0.74)). The most common reasons for non-function were missing battery (19%), missing alarm (17%), and battery disconnected (4%). Conclusions: Nearly half of the alarms installed were not working when tested 15 months later. Type of alarm and power source are important determinants of whether a household had a working alarm. What is already known on this topic Functioning smoke alarms can reduce the risk of death in the event of a house fire Many local authorities install smoke alarms in their properties Several different types of smoke alarm are available What this study adds Only half of the smoke alarms installed in local authority housing were still working 15 months later Ionising smoke alarms with long life lithium batteries were most likely to remain functioning Installing smoke alarms may not be an effective use of resources