A national surveillance study of childhood epilepsy mortality in the UK and Ireland.

BACKGROUND AND PURPOSE: Patients with epilepsy are significantly more likely to die prematurely than the general population, with causes ranging from associated comorbidities to sudden unexpected death in epilepsy (SUDEP). The aim was to estimate the UK and Ireland incidence of childhood epilepsy deaths and to describe case demographics and clinical characteristics. METHODS: This was a prospective, population-based surveillance study using established active surveillance methodology designed by the British Paediatric Surveillance Unit. RESULTS: Eighty-eight confirmed cases were reported with an overall annual incidence of 0.65 per 100 000 children aged <16 years (95% confidence interval 0.52-0.81). More cases were male (65%) and cases fell across all age groups, with more deaths reported in older children. Twenty-five per cent of deaths were epilepsy-related (including SUDEP); 75% of deaths were non-epilepsy-related. SUDEP was the most common cause of seizure-related deaths, accounting for 13 out of 17 children (76%). An underlying epilepsy syndrome was present in 36% of deaths, and 88% had global developmental delay. In addition, 90% of the children had comorbid conditions in addition to epilepsy. CONCLUSIONS: In this study, it has been demonstrated that death in children diagnosed with epilepsy occurs mainly in 'complicated epilepsy' secondary to factors associated with neurodisability, consolidating previous data. SUDEP is also a significant cause of paediatric epilepsy mortality that needs further attention. There is a clear need to better understand and reduce the number of epilepsy deaths in children in the UK, and national surveillance of SUDEP is warranted to better understand this entity in paediatric populations.

Can you detect early dementia from an email? A proof of principle study of daily computer use to detect cognitive and functional decline.

OBJECTIVE: To determine whether multiple computer use behaviours can distinguish between cognitively healthy older adults and those in the early stages of cognitive decline, and to investigate whether these behaviours are associated with cognitive and functional ability. METHODS: Older adults with cognitive impairment (n = 20) and healthy controls (n = 24) completed assessments of cognitive and functional abilities and a series of semi-directed computer tasks. Computer use behaviours were captured passively using bespoke software. RESULTS: The profile of computer use behaviours was significantly different in cognitively impaired compared with cognitively healthy control participants including more frequent pauses, slower typing, and a higher proportion of mouse clicks. These behaviours were significantly associated with performance on cognitive and functional assessments, in particular, those related to memory. CONCLUSION: Unobtrusively capturing computer use behaviours offers the potential for early detection of neurodegeneration in non-clinical settings, which could enable timely interventions to ultimately improve long-term outcomes.

Cancer risk in children born after donor ART.

STUDY QUESTION: Do children born after donor ART have an increased risk of developing childhood cancer in comparison to the general population? SUMMARY ANSWER: This study showed no overall increased risk of childhood cancer in individuals born after donor ART. WHAT IS KNOWN ALREADY: Most large population-based studies have shown no increase in overall childhood cancer incidence after non-donor ART; however, other studies have suggested small increased risks in specific cancer types, including haematological cancers. Cancer risk specifically in children born after donor ART has not been investigated to date. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study utilized record linkage to determine the outcome status of all children born in Great Britain (1992-2008) after donor ART. The cohort included 12 137 members who contributed 95 389 person-years of follow-up (average follow-up 7.86 years). PARTICIPANTS/MATERIALS, SETTING, METHODS: Records of all children born in Great Britain (England, Wales, Scotland) after all forms of donor ART (1992-2008) were linked to the UK National Registry of Childhood Tumours (NRCT) to determine the number who subsequently developed cancer by 15 years of age, by the end of 2008. Rates of overall and type specific cancer (selected a priori) were compared with age, sex and calendar year standardized population-based rates, stratifying for potential mediating/moderating factors including sex, age at diagnosis, birth weight, multiple births, maternal previous live births, assisted conception type and fresh/ cryopreserved cycles. MAIN RESULTS AND THE ROLE OF CHANCE: In our cohort of 12 137 children born after donor ART (52% male, 55% singleton births), no overall increased risk of cancer was identified. There were 12 cancers detected compared to 14.4 expected (standardized incidence ratio (SIR) 0.83; 95% CI 0.43-1.45; P = 0.50). A small, significant increased risk of hepatoblastoma was found, but the numbers and absolute risks were small (<5 cases observed; SIR 10.28; 95% CI 1.25-37.14; P < 0.05). This increased hepatoblastoma risk was associated with low birthweight. LIMITATIONS REASONS FOR CAUTION: Although this study includes a large number of children born after donor ART, the rarity of specific diagnostic subgroups of childhood cancer results in few cases and therefore wide CIs for such outcomes. As this is an observational study, it is not possible to adjust for all potential confounders; we have instead used stratification to explore potential moderating and mediating factors, where data were available. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to investigate cancer risk in children born after donor ART. Although based on small numbers, results are reassuring for families and clinicians. The small but significant increased risk of hepatoblastoma detected was associated with low birthweight, a known risk factor for this tumour type. It should be emphasized that the absolute risks are very small. However, on-going investigation with a longer follow-up is needed. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by Cancer Research UK (C36038/A12535) and the National Institute for Health Research (405526) and supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The work of the Childhood Cancer Research Group (CCRG) was supported by the charity CHILDREN with CANCER UK, the National Cancer Intelligence Network, the Scottish Government and the Department of Health for England and Wales. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Non-invasive respiratory support for infants with bronchiolitis: a national survey of practice.

BACKGROUND: Bronchiolitis is a common respiratory illness of early childhood. For most children it is a mild self-limiting disease but a small number of children develop respiratory failure. Nasal continuous positive airway pressure (nCPAP) has traditionally been used to provide non-invasive respiratory support in these children, but there is little clinical trial evidence to support its use. More recently, high-flow nasal cannula therapy (HFNC) has emerged as a novel respiratory support modality. Our study aims to describe current national practice and clinician preferences relating to use of non-invasive respiratory support (nCPAP and HFNC) in the management of infants (<12 months old) with acute bronchiolitis. METHODS: We performed a cross-sectional web-based survey of hospitals with inpatient paediatric facilities in England and Wales. Responses were elicited from one senior doctor and one senior nurse at each hospital. We analysed the proportion of hospitals using HFNC and nCPAP; clinical thresholds for their initiation; and clinician preferences regarding first-line support modality and future research. RESULTS: The survey was distributed to 117 of 171 eligible hospitals; 97 hospitals provided responses (response rate: 83%). The majority of hospitals were able to provide nCPAP (89/97, 91.7%) or HFNC (71/97, 73.2%); both were available at 65 hospitals (67%). nCPAP was more likely to be delivered in a ward setting in a general hospital, and in a high dependency setting in a tertiary centre. There were differences in the oxygenation and acidosis thresholds, and clinical triggers such as recurrent apnoeas or work of breathing that influenced clinical decisions, regarding when to start nCPAP or HFNC. More individual respondents with access to both modalities (74/106, 69.8%) would choose HFNC over nCPAP as their first-line treatment option in a deteriorating child with bronchiolitis. CONCLUSIONS: Despite lack of randomised trial evidence, nCPAP and HFNC are commonly used in British hospitals to support infants with acute bronchiolitis. HFNC appears to be currently the preferred first-line modality for non-invasive respiratory support due to perceived ease of use.

Modelling the Evolution of Social Structure.

Although simple social structures are more common in animal societies, some taxa (mainly mammals) have complex, multi-level social systems, in which the levels reflect differential association. We develop a simulation model to explore the conditions under which multi-level social systems of this kind evolve. Our model focuses on the evolutionary trade-offs between foraging and social interaction, and explores the impact of alternative strategies for distributing social interaction, with fitness criteria for wellbeing, alliance formation, risk, stress and access to food resources that reward social strategies differentially. The results suggest that multi-level social structures characterised by a few strong relationships, more medium ties and large numbers of weak ties emerge only in a small part of the overall fitness landscape, namely where there are significant fitness benefits from wellbeing and alliance formation and there are high levels of social interaction. In contrast, 'favour-the-few' strategies are more competitive under a wide range of fitness conditions, including those producing homogeneous, single-level societies of the kind found in many birds and mammals. The simulations suggest that the development of complex, multi-level social structures of the kind found in many primates (including humans) depends on a capacity for high investment in social time, preferential social interaction strategies, high mortality risk and/or differential reproduction. These conditions are characteristic of only a few mammalian taxa.

CCL2 release by airway smooth muscle is increased in asthma and promotes fibrocyte migration.

BACKGROUND: Asthma is characterized by variable airflow obstruction, airway inflammation, airway hyper-responsiveness and airway remodelling. Airway smooth muscle (ASM) hyperplasia is a feature of airway remodelling and contributes to bronchial wall thickening. We sought to investigate the expression levels of chemokines in primary cultures of ASM cells from asthmatics vs healthy controls and to assess whether differentially expressed chemokines (i) promote fibrocyte (FC) migration towards ASM and (ii) are increased in blood from subjects with asthma and in sputum samples from those asthmatics with bronchial wall thickening. METHODS: Chemokine concentrations released by primary ASM were measured by MesoScale Discovery platform. The chemokine most highly expressed by ASM from asthmatics compared with healthy controls was confirmed by ELISA, and expression of its cognate chemokine receptor by FCs was examined by immunofluorescence and flow cytometry. The role of this chemokine in FC migration towards ASM was investigated by chemotaxis assays. RESULTS: Chemokine (C-C motif) ligand 2 (CCL2) levels were increased in primary ASM supernatants from asthmatics compared with healthy controls. CCR2 was expressed on FCs. Fibrocytes migrated towards recombinant CCL2 and ASM supernatants. These effects were inhibited by CCL2 neutralization. CCL2 levels were increased in blood from asthmatics compared with healthy controls, and sputum CCL2 was increased in asthmatics with bronchial wall thickening. CONCLUSIONS: Airway smooth muscle-derived CCL2 mediates FC migration and potentially contributes to the development of ASM hyperplasia in asthma.

Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial.

OBJECTIVE: To assess the effectiveness and safety of melatonin in treating severe sleep problems in children with neurodevelopmental disorders. DESIGN: 12 week double masked randomised placebo controlled phase III trial. SETTING: 19 hospitals across England and Wales. PARTICIPANTS: 146 children aged 3 years to 15 years 8 months were randomised. They had a range of neurological and developmental disorders and a severe sleep problem that had not responded to a standardised sleep behaviour advice booklet provided to parents four to six weeks before randomisation. A sleep problem was defined as the child not falling asleep within one hour of lights out or having less than six hours' continuous sleep. INTERVENTIONS: Immediate release melatonin or matching placebo capsules administered 45 minutes before the child's bedtime for a period of 12 weeks. All children started with a 0.5 mg capsule, which was increased through 2 mg, 6 mg, and 12 mg depending on their response to treatment. MAIN OUTCOME MEASURES: Total sleep time at night after 12 weeks adjusted for baseline recorded in sleep diaries completed by the parent. Secondary outcomes included sleep onset latency, assessments of child behaviour, family functioning, and adverse events. Sleep was measured with diaries and actigraphy. RESULTS: Melatonin increased total sleep time by 22.4 minutes (95% confidence interval 0.5 to 44.3 minutes) measured by sleep diaries (n=110) and 13.3 (-15.5 to 42.2) measured by actigraphy (n=59). Melatonin reduced sleep onset latency measured by sleep diaries (-37.5 minutes, -55.3 to -19.7 minutes) and actigraphy (-45.3 minutes, -68.8 to -21.9 minutes) and was most effective for children with the longest sleep latency (P=0.009). Melatonin was associated with earlier waking times than placebo (29.9 minutes, 13.6 to 46.3 minutes). Child behaviour and family functioning outcomes showed some improvement and favoured use of melatonin. Adverse events were mild and similar between the two groups. CONCLUSIONS: Children gained little additional sleep on melatonin; though they fell asleep significantly faster, waking times became earlier. Child behaviour and family functioning outcomes did not significantly improve. Melatonin was tolerable over this three month period. Comparisons with slow release melatonin preparations or melatonin analogues are required. TRIAL REGISTRATION: ISRCT No 05534585.

The use of MElatonin in children with neurodevelopmental disorders and impaired sleep: a randomised, double-blind, placebo-controlled, parallel study (MENDS).

BACKGROUND: Difficulties in initiating and maintaining sleep are common in children with neurodevelopmental disorders. Melatonin is unlicensed in children yet widely prescribed for sleep problems. OBJECTIVE: To determine whether or not immediate-release melatonin is beneficial compared with placebo in improving total duration of night-time sleep in children with neurodevelopmental problems. DESIGN: Randomised, double-blind, placebo-controlled, parallel study. SETTING: Hospitals throughout England and Wales recruited patients referred by community paediatricians and other clinical colleagues. PARTICIPANTS: Children with neurodevelopmental problems aged from 3 years to 15 years 8 months who did not fall asleep within 1 hour of lights out or who had < 6 hours of continuous sleep. Before randomisation, patients meeting eligibility criteria entered a 4- to 6-week behaviour therapy period in which a behaviour therapy advice booklet was provided. Sleep was measured using sleep diaries and actigraphy. After this period the sleep diaries were reviewed to determine if the sleep problem fulfilled the eligibility criteria. Eligible participants were randomised and followed for 12 weeks. INTERVENTIONS: Melatonin or placebo capsules in doses of 0.5 mg, 2 mg, 6 mg and 12 mg for a period of 12 weeks. The starting dose was 0.5 mg and the dose could be escalated through 2 mg and 6 mg to 12 mg during the first 4 weeks, at the end of which the child was maintained on that dose. MAIN OUTCOME MEASURES: The primary outcome was total night-time sleep time (TST) calculated using sleep diaries at 12 weeks compared with baseline. Secondary outcome measures included TST calculated using actigraphy data, sleep-onset latency (SOL) (time taken to fall asleep), sleep efficiency, Composite Sleep Disturbance Index score, global measure of child's sleep quality, Aberrant Behaviour Checklist, Family Impact Module of the Pediatric Quality of Life Inventory (PedsQL™), the Epworth Sleepiness Scale, number and severity of seizures and adverse events. Salivary melatonin concentrations and association of genetic variants with abnormal melatonin production were also investigated. RESULTS: A total of 275 children were screened to enter the trial; 263 (96%) children were registered and completed the 4- to 6-week behaviour therapy period and 146 (56%) children were randomised, of whom 110 (75%) contributed data for the primary outcome. The difference in TST time between the melatonin and placebo groups adjusted for baseline was 22.43 minutes [95% confidence interval (CI) 0.52 to 44.34 minutes; p = 0.04] measured using sleep diaries. A reduction in SOL, adjusted for baseline, was seen for melatonin compared with placebo when measured by sleep diaries (-37.49 minutes, 95% CI -55.27 to -19.71 minutes; p < 0.0001) and actigraphy (-45.34 minutes, 95% CI -68.75 to -21.93 minutes; p = 0.0003). There were no significant differences between the two groups in terms of the reporting of adverse events. The results of other secondary outcomes favoured melatonin but were not statistically significant. CONCLUSIONS: On average, the children treated with melatonin slept 23 minutes longer than those in the placebo group; however, the upper limit of the confidence interval was less than 1 hour, the minimum clinically worthwhile difference specified at the outset of the trial. Melatonin is effective in reducing SOL in children with neurodevelopmental delay by a mean of 45 minutes; a value of 30 minutes was specified a priori to be clinically important. Future studies should be conducted over longer periods and directly compare different formulations of melatonin with conventional hypnotic and sedative medications. It would also be important to study groups of children with specific neurological disorders. TRIAL REGISTRATION: Current Controlled Trials ISRCTN05534585. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 40. See the HTA programme website for further project information.

How reliably can paediatric professionals identify pale stool from cholestatic newborns?

BACKGROUND: The success of surgery in infants with hepatobiliary disease is inversely proportional to the age when surgery was performed. Pale stool colour is a major indicator of biliary obstruction. However, simple recognition has been inadequate, resulting in late diagnosis and referral. Objective To assess the skills of healthcare professionals in recognising pale stools. METHOD: Photographs of normal, acholic and indeterminate infant stools were shown to paediatric professionals who have regular contact with jaundiced babies at three London teaching hospitals. Each stool was classified as 'healthy' or 'suspect'. RESULTS: One-third of the stools were not correctly identified by physicians and nurses. CONCLUSION: Experienced professionals often do not recognise stool colour associated with biliary obstruction. The authors propose that stool colour cards similar to those used in Japan and Taiwan may improve early detection of hepatobiliary disease at a minimal cost.

Prospective surveillance study of the management of intussusception in UK and Irish infants.

BACKGROUND: Intussusception is the most common cause of acute intestinal obstruction in infants. This study examined the clinical presentation, management and outcomes of intussusception in this age group. METHODS: Prospective surveillance of intussusception in infants was carried out between March 2008 and March 2009 in the UK and Ireland. Monthly cards were sent to paediatric clinicians who were requested to notify cases of intussusception. RESULTS: The study identified 261 confirmed cases. The commonest presenting symptom/sign was non-bilious vomiting, in 210 (80·5 per cent) of the infants. Abdominal ultrasonography was done in 247 infants (94·6 per cent) and was diagnostic in 242 (98·0 per cent), compared with plain abdominal X-ray, which was diagnostic in 33 (23·6 per cent) of 140 infants. Enema reduction was carried out in 240 (92·0 per cent) of the 261 infants; the majority (237, 98·8 per cent) had pneumatic reduction with a success rate of 61·2 per cent (145 of 237). Surgery was required in 111 infants (42·5 per cent); 92 operations were as a result of unsuccessful enema reduction, and the remaining 19 infants (17·1 per cent) had primary surgery. Forty-four infants (39·6 per cent of operations) needed a bowel resection. The majority of children (238, 91·2 per cent) recovered uneventfully; 21 (8·0 per cent) had sequelae, one child died (0·4 per cent), and the outcome was unknown for one infant. CONCLUSION: This study described current treatment patterns for intussusception in infancy; these represent a benchmark for improved standards of care for this condition.

General anaesthesia for deep brain stimulator electrode insertion in Parkinson's disease.

BACKGROUND: This paper compares the use of general and local anaesthetic in patients having deep brain stimulator (DBS) surgery. It is a retrospective case note study of 46 patients treated consecutively with subthalamic nucleus stimulation for Parkinson's disease as practise changed in a Neurosurgical unit. METHODS: The first 20 patients (LA group) had permanent electrodes placed under local anaesthesia. The remaining 26 patients (GA group) had the entire procedure under general anaesthesia. The groups were similar for age, sex, duration of Parkinson's disease and preoperative levodopa requirement. RESULTS: The clinical results were similar in that within each group, the reduction in levodopa was not only clinically but also statistically significant (p < 0.001 for both, paired t test): for the LA group, the 6-month requirement was 39.4% (29.5-52.6%) of the preoperative requirement and for the GA group, the 6-month requirement was 32.3% (25.2-41.5%) of the preoperative requirement. The reduction in levodopa was maintained at 1 year. Of note, duration of surgery and length of stay were reduced. The mean duration of surgery was 8.2 h (7.8-8.6) for the LA group and 7.5 h (7.2-7.8) for the GA group (p = 0.003). The geometric mean of length of hospital stay was 5.4 days(4.6-6.3) for the LA group and 3.8 days (3.4-4.4) for the GA group (p = 0.001) There was no difference in electrophysiological recording. CONCLUSION: This study describes benefits in the GA group for the entire procedure of STN DBS. In these samples, there was no difference in the adverse effects seen in patients undergoing deep brain stimulator insertion with general anaesthetic compared with local anaesthetic. The use of general anaesthetic did not detract from the known benefits of surgery.

Supporting creativity and appreciation of uncertainty in exploring geo-coded public health data.

BACKGROUND AND OBJECTIVES: We present a prototype visualisation tool, ADVISES (Adaptive Visualization for e-Science), designed to support epidemiologists and public health practitioners in exploring geo-coded datasets and generating spatial epidemiological hypotheses. The tool is designed to support creative thinking while providing the means for the user to evaluate the validity of the visualization in terms of statistical uncertainty. We present an overview of the application and the results of an evaluation exploring public health researchers' responses to maps as a new way of viewing familiar data, in particular the use of thematic maps with adjoining descriptive statistics and forest plots to support the generation and evaluation of new hypotheses. METHODS: A series of qualitative evaluations involved one experienced researcher asking 21 volunteers to interact with the system to perform a series of relatively complex, realistic map-building and exploration tasks, using a 'think aloud' protocol, followed by a semi-structured interview The volunteers were academic epidemiologists and UK National Health Service analysts. RESULTS: All users quickly and confidently created maps, and went on to spend substantial amounts of time exploring and interacting with system, generating hypotheses about their maps. CONCLUSIONS: Our findings suggest that the tool is able to support creativity and statistical appreciation among public health professionals and epidemiologists building thematic maps. Software such as this, introduced appropriately, could increase the capability of existing personnel for generating public health intelligence.

Serial NT-proBNP measurements for risk stratification of patients with decompensated heart failure.

PURPOSE: NT-proBNP is an important prognostic predictor in patients with heart failure. However, it is unknown whether a change of NT-proBNP plasma levels in the early phase of decompensation might be of additional prognostic value in patients with acute decompensation of heart failure. METHODS AND RESULTS: NT-proBNP plasma levels of 116 patients with decompensated heart failure from ischemic/non-ischemic origin were measured at baseline and at 12, 24 and 48 h after hospital admission. Baseline levels and changes of plasma levels within the first 48 h were correlated with 30-day mortality. In all patients, NT-proBNP 12 h after admission was highest and superior with respect to the prediction of 30-day mortality compared to plasma levels on admission. In total, 38 patients died within the first 30 days. In these patients absolute NT-proBNP plasma levels were significantly higher and the increase within 12 h after admission was more pronounced compared to survivors (p<0.001). NT-proBNP at 12 h after admission also had the highest predictive value for the 30-day mortality rate in patients with acute myocardial infarction. The increase of NT-proBNP plasma levels within 12 h after admission had the highest predictive value in patients suffering from decompensated heart failure. CONCLUSIONS: NT-proBNP is a powerful marker of 30-day mortality in patients with decompensated heart failure of ischemic and non-ischemic origin. Compared with single baseline measurements, serial measurements of NT-proBNP plasma levels within 12 h after hospital admission may be used to increase the predictive value of NT-proBNP with regard to the early identification of patients who are at high risk of mortality.

Perturbations in finger length and digit ratio (2D:4D) in ICSI children.

Intracytoplasmic sperm injection (ICSI) is used to overcome severe male-factor infertility where males are azoospermic or have poor quality spermatozoa. Perturbations of finger length (short finger length adjusted for height and high second-to-fourth digit ratio, or 2D:4D) have been described in azoospermic men and men who are rated as having low sexual attractiveness. High 2D:4D has been described in women with high fecundity. Such perturbations may be related to endocrine regulation of some homeobox genes. This study compared finger length and 2D:4D in singleton children conceived with the help of ICSI with those in naturally conceived singleton controls. Participants were recruited from centres in Germany and the UK. There were 211 children conceived by ICSI and 195 controls. Finger length was measured from photocopies of the ventral surface of the hand. In comparison to controls, male and female ICSI children had shorter fingers after correction for height. There was also evidence that female ICSI children may have higher 2D:4D than female controls. Perturbations in finger length in ICSI children may be inherited from their fathers and, in the case of boys, could be associated with lower fertility and reduced sexual attractiveness. For ICSI females, increased 2D:4D may be associated with increased fertility.

Assessment of vision and hearing in children conceived spontaneously and by ICSI: a prospective controlled, single-blinded follow-up study.

Long-term follow-up studies on the health of children born after assisted reproduction technologies are mandatory. Vision and hearing are the most important senses that continue to develop during childhood. There are few reports on vision and hearing in preschool children born after assisted conception. This prospective controlled blinded follow-up study examined 276 term-born singleton intracytoplasmic injection (ICSI) children and 273 spontaneously conceived controls at a mean age of 5.5 years and performed detailed vision and hearing test and clinically examined eyes and ears. There was no significant difference between ICSI and control children regarding the occurrence of vision or hearing impairments. Unsurprisingly, children with abnormalities in otoscopy were more likely to have an abnormal hearing test compared with children without abnormalities. Only 8.5% of ICSI parents and 25.4% of control parents whose children showed an abnormal hearing test knew about the hearing problems of their child. In conclusion, there was no difference in the development of hearing and vision in ICSI children and spontaneously conceived controls. But only few parents knew about hearing problems of their child after undergoing routine screening examinations. Parental interviews would therefore not be sufficient in order to assess vision and hearing in follow-up studies.

Airway smooth muscle proliferation and survival is not modulated by mast cells.

BACKGROUND: Airway smooth muscle (ASM) hyperplasia and mast cell localization within the ASM bundle are important features of asthma. The cause of this increased ASM mass is uncertain and whether it is a consequence of ASM-mast cell interactions is unknown. OBJECTIVE: We sought to investigate ASM proliferation and survival in asthma and the effects of co-culture with mast cells. METHODS: Primary ASM cultures were derived from 11 subjects with asthma and 12 non-asthmatic controls. ASM cells were cultured for up to 10 days in the presence or absence of serum either alone or in co-culture with the human mast cell line-1, unstimulated human lung mast cells (HLMC) or IgE/anti-IgE-activated HLMC. Proliferation was assessed by cell counts, CFSE assay and thymidine incorporation. Apoptosis and necrosis were analysed by Annexin V/propidium iodide staining using flow cytometry and by assessment of nuclear morphology using immunofluorescence. Mast cell activation was confirmed by the measurement of histamine release. RESULTS: Using a number of techniques, we found that ASM proliferation and survival was not significantly different between cells derived from subjects with or without asthma. Co-culture with mast cells did not affect the rate of proliferation or survival of ASM cells. CONCLUSION: Our findings do not support a role for increased airway smooth proliferation and survival as the major mechanism driving ASM hyperplasia in asthma.

Airway smooth muscle chemokine receptor expression and function in asthma.

BACKGROUND: Chemokine receptors play an important role in cell migration and wound repair. In asthma, CCR3 and 7 are expressed by airway smooth muscle (ASM) and CCR7 has been implicated in the development of ASM hyperplasia. The expression profile of other chemokine receptors by ASM and their function needs to be further explored. OBJECTIVE: We sought to investigate ASM chemokine receptor expression and function in asthma. METHODS: ASM cells were derived from 17 subjects with asthma and 36 non-asthmatic controls. ASM chemokine receptor expression was assessed by flow cytometry and immunofluorescence. The function of chemokine receptors expressed by more than 10% of ASM cells was investigated by intracellular calcium measurements, chemotaxis, wound healing, proliferation and survival assays. RESULTS: In addition to CCR3 and 7, CXCR1, 3 and 4 were highly expressed by ASM. These CXC chemokine receptors were functional with an increase in intracellular calcium following ligand activation and promotion of wound healing [CXCL10 (100 ng/mL) 34 +/- 2 cells/high-powered field (hpf) vs. control 29 +/- 1; P=0.03; n=8]. Spontaneous wound healing was inhibited by CXCR3 neutralizing antibody (mean difference 7 +/- 3 cells/hpf; P=0.03; n=3). CXC chemokine receptor activation did not modulate ASM chemotaxis, proliferation or survival. No differences in chemokine receptor expression or function were observed between ASM cells derived from asthmatic or non-asthmatic donors. CONCLUSIONS: Our findings suggest that the chemokine receptors CXCR1, 3 and 4 modulate some aspects of ASM function but their importance in asthma is uncertain.

Follow-up of children born after ART.

Assisted reproductive therapies (ART), namely in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), have become widely used in the treatment of human infertility. Children conceived using ART represent a substantial proportion of the population. Follow-up of these children is necessary in order to evaluate the risks of infertility treatment upon subsequently conceived offspring. In recent years there has been considerable work in this field. This review summarises current evidence regarding the health of children conceived following ART, encompassing neonatal outcomes, the risk of congenital malformations, neurodevelopmental outcome, physical health, psychosocial well being, and the risk of cancer. The main risks for the future well being of ART children remain multiple pregnancies and low birth weight. Evidence regarding the outcome of singletons born at term following ART is generally reassuring. It is essential that follow-up of ART children continues as they progress through adolescence into adulthood.

Spontaneous pregnancy after successful ICSI treatment: evaluation of risk factors in 899 families in Germany.

There are only scarce data on the incidence of spontaneous pregnancy in infertility patients. Contraception after infertility treatment is another topic that has been neglected so far. Therefore, a questionnaire was sent to 1614 couples with a child conceived by intracytoplasmic sperm injection (ICSI) aged 4-6 years. A total of 899 couples responded (response rate 55.7%). A total of 10.9% of couples had used contraception. Of the couples that had actively tried to conceive, 20.0% had conceived spontaneously, resulting in a live-birth rate of 16.4%. 74.5% of these pregnancies were conceived within 2 years after delivery. A further 26.6% of couples conceived again by ICSI, with a live-birth rate of 20.9%. Maternal age was the only prognostic factor for spontaneous conception. Parents of multiples after ICSI did not have a higher chance of spontaneous conception than parents of singletons. Couples can be counselled that one out of five couples conceive spontaneously after successful ICSI. Even when assuming that none of the families that were lost to follow-up had conceived spontaneously, one out of eight couples would have conceived spontaneously. Therefore, it is important to counsel patients about the possibility of natural conception and necessity to use contraception despite their history of subfertility.