Sensorineural hearing loss is the most frequent sensory deficit of childhood and is of genetic origin in up to 75% of cases. It has been shown that mutations of the SLC26A4 (PDS) gene were involved in syndromic deafness characterized by congenital sensorineural hearing impairment and goitre (Pendred's syndrome), as well as in congenital isolated deafness (DFNB4). While the prevalence of SLC26A4 mutations in Pendred's syndrome is clearly established, it remains to be studied in large cohorts of patients with nonsyndromic deafness and detailed clinical informations. In this report, 109 patients from 100 unrelated families, aged from 1 to 32 years (median age: 10 years), with nonsyndromic deafness and enlarged vestibular aqueduct, were genotyped for SLC26A4 using DHPLC molecular screening and sequencing. In all, 91 allelic variants were observed in 100 unrelated families, of which 19 have never been reported. The prevalence of SLC26A4 mutations was 40% (40/100), with biallelic mutation in 24% (24/100), while six families were homozygous. All patients included in this series had documented deafness, associated with EVA and without any evidence of syndromic disease. Among patients with SLC26A4 biallelic mutations, deafness was more severe, fluctuated more than in patients with no mutation. In conclusion, the incidence of SLC26A4 mutations is high in patients with isolated deafness and enlarged vestibular aqueduct and could represent up to 4% of nonsyndromic hearing impairment. SLC26A4 could be the second most frequent gene implicated in nonsyndromic deafness after GJB2, in this Caucasian population.

Objective.: Although the equimolecular mixture of oxygen and nitrous oxide (EMONO) seems a good choice to relieve procedure-related pain in children, it has not been accepted everywhere. In France, the rapid spread of its use has elicited suspicion and doubts regarding its safety. To assess the use and the safety of this gas mixture in the pediatric settings in France, we conducted a national survey.Methodology.: Centers that had accepted a nation- wide invitation to participate in the survey filled out a questionnaire after each EMONO administration during a 2-month study. Procedure and inhalation characteristics, as well as pain evaluations and side effects, were reported.Results.: One thousand nineteen EMONO inhalations from 31 centers that agreed to participate in this 2-month survey were analyzed. Median (range) age was 6.4 (0–18) years. Four percent (46) of children were 12 months old or younger, 29% (295) were 5 years old or younger, 45% (459) were 6 to 10 years old, and 26% (265) were older than 10 years of age.The procedures performed with EMONO inhalation were: lumbar punctures (286), bone marrow aspirations (BMA; 231), laceration repairs (215), minor procedures (75), minor surgery (53), punctures (49), fractures (45), dental care (43), and pulmonary endoscopy (22). Nine percent of procedures were undertaken without the presence of a physician; the child being observed only by the attending nurse. A drug association was noted in 182 (17.9%) of procedures: midazolam (63%), acetaminophen (18%), nalbuphine (8.5%), hydroxyzine (5%), flunitrazepam (2%), chlorazepate (2%), morphine (1%), and lorazepam (.5%). EMLA cream (Astra) was applied in 98.6% of lumbar punctures, 93.7% of BMA, and 54.2% of punctures including lymph nodes, hematoma, or renal biopsies. Lidocaine infiltration was performed in 51% of minor surgery procedures, 40% of laceration repairs, and 28% of BMA.The inhalation system included a whistle, a scented mask, and a nonrebreathing respiratory valve in 48.9%, 71.2%, and 78.3% of the patients, respectively. Initial physical restraint was needed in 18.2% of all the patients. Inhalation refusal was noted in 129 (12.7%) children; of these, 53 had an alternative method of analgesia (EMLA or lidocaine infiltration), 15 had no other analgesia, and in the remaining 61, EMONO inhalation was maintained against the child's will.Median (interquartile) inhalation length was 4 (3–5) minutes before starting the procedure and 6 (6–15) minutes for the total inhalation.Median (interquartile) procedural pain evaluations were 9 (0–30) for children on a 0 to 100 visual analog scale, 1 (0–3) for both nurses and parents on a 0 to 10 numerical scale. Median (interquartile) procedural pain as evaluated by nurses for the 3 most frequent procedures were 0 (0–2) for lumbar punctures, 2 (0–4) for bone marrow aspiration, and 2 (0–4) for laceration repair. Comparison of pain assessed by nurses in children 3 years old or younger and those older than 3 years of age showed a median (range) score of 2 (0–10) versus 1 (0–10), respectively. Pain self-assessment was completed in 647 children 6 years of age or older. Median (interquartile) children pain assessments were as follows: lumbar puncture (5; 0–20), bone marrow aspiration (12.5; 0–40), laceration repair (12; 0–40), minor procedures (18; 0–32), minor surgery (10; 0–35), punctures (0; 0–18), fracture (15; 0–30), dental care (20; 0–40), and pulmonary endoscopy (15; 0–30). Ninety-three percent of the 647 children who were able to answer the question said they would accept EMONO analgesia if a new procedure were to be performed. Behavioral reactions during procedures varied with age of the child; cry was observed in 44.1%, 24.4%, 12.9%, and 11.2% of children 3 years or younger, 4 to 6 years, 7 to 10 years, and 11 years or older, respectively. Physical restraint was necessary in 34.2%, 22%, 13.5%, and 8.4% of children aged 3 years or younger, 4 to 6 years, 7 to 10 years, and 11 years or older, respectively.Staff satisfaction regarding EMONO efficacy was as follows: very satisfied (56.7%), satisfied (31.3%), not satisfied (8.6%), and very unsatisfied (3.3%). Minor side effects were observed during 381 (37%) inhalations. These side effects were euphoria (20.1%), change in visual or auditory perception (7.0%), dreams (5.7%), nausea and vomiting (3.7%), deep sedation (2.1%), paresthesia (1.7%), dizziness (1.6%), restlessness (1.5%), nightmares and hallucinations (1.2%), and miscellaneous (1.9%). All side effects were transient and vanished within 5 minutes after removing the inhalation device. No serious side effects were noted.Conclusions.: This survey shows that EMONO is used to provide analgesia in a great variety of procedures. Although analgesia obtained during procedures is good, this gas mixture is not efficacious in all patients. Therefore, physicians should quickly detect failures to switch to another analgesic approach. The best results are obtained in children 3 years of age or older. Although minor effects are frequent during EMONO inhalation, its use seems very safe because no single serious side effect was noted during this study. This helpful method is still underused, and it should be readily available in each emergency and pediatric department.

Most studies of neighborhood effects on health have used the multilevel approach. However, since this methodology does not incorporate any notion of space, it may not provide optimal epidemiologic information when modeling variations or when investigating associations between contextual factors and health. Investigating mental disorders due to psychoactive substance use among all 65,830 individuals aged 40–59 years in 2001 in Malmö, Sweden, geolocated at their place of residence, the authors compared a spatial analytical perspective, which builds notions of space into hypotheses and methods, with the multilevel approach. Geoadditive models provided precise cartographic information on spatial variations in prevalence independent of administrative boundaries. The multilevel model showed significant neighborhood variations in the prevalence of substance-related disorders. However, hierarchical geostatistical models provided information on not only the magnitude but also the scale of neighborhood variations, indicating a significant correlation between neighborhoods in close proximity to each other. The prevalence of disorders increased with neighborhood deprivation. Far stronger associations were observed when using indicators measured in spatially adaptive areas, centered on residences of individuals, smaller in size than administrative neighborhoods. In neighborhood studies, building notions of space into analytical procedures may yield more comprehensive information than heretofore has been gathered on the spatial distribution of outcomes.

Study objective: Most studies of place effects on health have followed the multilevel analytical approach that investigates geographical variations of health phenomena by fragmenting space into arbitrary areas. This study examined whether analysing geographical variations across continuous space with spatial modelling techniques and contextual indicators that capture space as a continuous dimension surrounding individual residences provided more relevant information on the spatial distribution of outcomes. Healthcare utilisation in France was taken as an illustrative example in comparing the spatial approach with the multilevel approach. Design: Multilevel and spatial analyses of cross sectional data. Participants: 10 955 beneficiaries of the three principal national health insurance funds, surveyed in 1998 and 2000 on continental France. Main results: Multilevel models showed significant geographical variations in healthcare utilisation. However, the Moran’s I statistic showed spatial autocorrelation unaccounted for by multilevel models. Modelling the correlation between people as a decreasing function of the spatial distance between them, spatial mixed models gave information not only on the magnitude, but also on the scale of spatial variations, and provided more accurate standard errors for risk factors effects. The socioeconomic level of the residential context and the supply of physicians were independently associated with healthcare utilisation. Place indicators better explained spatial variations in healthcare utilisation when measured across continuous space, rather than within administrative areas. Conclusions: The kind of conceptualisation of space during analysis influences the understanding of place effects on health. In many contextual studies, viewing space as a continuum may yield more relevant information on the spatial distribution of outcomes.