Inactivation of ricin by constituents present in a skin decontamination lotion.

Ricin is a proteinaceous toxin, listed on the schedules of both the chemical and biological weapons conventions. The ease of accessibility to the Ricinus communis plant and toxin extraction makes ricin a viable concern for use of intentional release and causal effects. The adverse effects following exposure to the toxin are caused by the bipartite molecular structure of ricin which allows binding to the mammalian cell surface, enter via endocytic uptake, and deliver the catalytically active polypeptide into the cell cytosol where it irreversibly inhibits protein synthesis, causing cell death. In the present study, the inactivation effectiveness of RSDL® (Reactive Skin Decontamination Lotion) and its individual inactivating constituents (Potassium 2,3-butanedione monoximate (KBDO) and 2,3-butanedione (DAM)) was evaluated for ricin using a number of read out systems including a cytotoxicity assay, quantitative sandwich ELISA test, and a mass spectrometry-based assay. The results demonstrate that RSDL is able to abolish ricin activity after an incubation time of 30 min as determined in the cytotoxicity assay, and after 2 min as determined in the ELISA assay. Mass spectrometric analysis provided evidence that RSDL is able to induce cleavage of the disulfide linkage between the A- and B- polypeptide chain of ricin which is crucial to the inactivation of the toxin, but this seems not the only mechanism of inactivation. Follow on studies would assist to elucidate the details of the toxin inactivation because it is possible that additional generic mechanisms are in place for denaturation with the RSDL lotion components. This may also provide a promise for testing and inactivation with RSDL of other protein toxins.

Clinical experience of paediatric self-expanding foam cuffed tracheostomy tubes.

INTRODUCTION: Use of self-expanding foam-filled tracheostomy tube cuffs (Bivona® FOME cuf®) in paediatrics has become a recent practice within our institution for patients with intractable aspiration. The current literature, clinical indications and subsequent management is lacking. We present our experience with a cohort of children with a foam-cuffed tracheostomy tube managed at Great Ormond Street Hospital, describing their indications and outcomes, as well as routine and emergency management. METHOD: Our tracheostomy patient population was reviewed and those with a Bivona® FOME cuf® tracheostomy tube were identified and reviewed. The indications for foam-cuffed tracheostomy tube insertion, progress, and further management, including emergency care, were reviewed. RESULTS: Ten patients were identified, all with a chronic history of respiratory infections secondary to aspiration being the leading indication. All patients had an ongoing improvement in their chest function following insertion with no episodes of cuff trauma. One patient had difficulty when a port line was accidently cut, which resulted in difficulty of removal, and we outline a strategy for dealing with this. CONCLUSION: The foam-cuffed tracheostomy tube is a useful tracheostomy tube to use in the management of chronic aspiration in children with poor chest health, however due to the lack of knowledge and experience they can prove to be a difficult tube to manage. Further educational information should be available as to the indications, routine care and emergency management of Bivona® FOME cuf® tracheostomy tubes. We believe they represent a useful option for institutions to consider in the paediatric population.

Decontamination of Toxic Industrial Chemicals and Fentanyl by Application of the RSDL® Kit.

PURPOSE: This study investigated the decontamination effectiveness of selected toxic industrial chemicals using RSDL® (Reactive Skin Decontamination Lotion Kit; Emergent BioSolutions Inc.; https://www.rsdl.com/). MATERIALS AND METHODS: Quantitative analytical methods were developed for dermal toxic compounds of varying physicochemical properties: sulfuric acid, hydrofluoric acid, ammonia, methylamine, hydrazine, phenylhydrazine, 1,2-dibromoethane, capsaicin, and fentanyl. These methods were subsequently used to evaluate the decontamination effectiveness on painted metal substrates at an initial chemical contamination level of 10g/m2 (0.1g/m2 for fentanyl). RESULTS: The decontamination effectiveness ranged from 97.79% to 99.99%. DISCUSSION AND CONCLUSION: This study indicates that the RSDL kit may be amenable for use as an effective decontaminant for material substrates beyond the classical chemical warfare agents and the analytical methods may be used for future decontamination assessment studies using contaminated skin or other materials.

Paediatric tracheostomy tubes: recent developments and our current practice.

OBJECTIVE: A variety of paediatric tracheostomy tubes are available. This article reviews the tubes in current use at Great Ormond Street Hospital for Children and Evelina London Children's Hospital. METHODS: This paper outlines our current preferences, and the particular indications for different tracheostomy tubes, speaking valves and other attachments. RESULTS: Our preferred types of tubes have undergone significant design changes. This paper also reports further experience with certain tubes that may be useful in particular circumstances. An updated sizing chart is included for reference purposes. CONCLUSION: The choice of a paediatric tracheostomy tube remains largely determined by individual clinical requirements. Although we still favour a small range of tubes for use in the majority of our patients, there are circumstances in which other varieties are indicated.

Computed tomography versus magnetic resonance imaging in paediatric cochlear implant assessment: a pilot study and our experience at Great Ormond Street Hospital.

BACKGROUND: To date, there is a lack of consensus regarding the use of both computed tomography and magnetic resonance imaging in the pre-operative assessment of cochlear implant candidates. METHODS: Twenty-five patients underwent high-resolution computed tomography and magnetic resonance imaging. 'Control scores' describing the expected visualisation of specific features by computed tomography and magnetic resonance imaging were established. An independent radiological review of all computed tomography and magnetic resonance imaging scan features was then compared to the control scores and the findings recorded. RESULTS: Agreement with control scores occurred in 83 per cent (20 out of 24) of computed tomography scans and 91 per cent (21 out of 23) of magnetic resonance imaging scans. Radiological abnormalities were demonstrated in 16 per cent of brain scans and 18 per cent of temporal bone investigations. CONCLUSION: Assessment in the paediatric setting constitutes a special situation given the likelihood of congenital temporal bone abnormalities and associated co-morbidities that may be relevant to surgery and prognosis following cochlear implantation. Both computed tomography and magnetic resonance imaging contribute valuable information and remain necessary in paediatric cochlear implant pre-operative assessment.

Paediatric injection medialisation laryngoplasty: Recent Great Ormond Street Hospital experience.

INTRODUCTION: Unilateral vocal fold paresis may significantly impair the vocal quality and laryngeal competence of a child. Relatively little literature relates to injection medialisation laryngoplasty (IML) in children and previous reports have involved small numbers of heterogenous cases. METHODS: A retrospective review was conducted of paediatric patients managed by our multidisciplinary specialist voice clinic undergoing IML for unilateral vocal fold paresis. Cases of bilateral paresis, those characterised by vocal fold fixation, and patients without formal pre and post-operative voice evaluation were excluded. RESULTS: Eighteen IML procedures were performed in 12 children eligible for inclusion between 2005 and 2015. The average age at time of procedure was 12 years (range 9-15 years). Autologous fat was used in 5 procedures, succeeded by calcium hydroxylapatite (Radiesse® Voice) from 2011 (n = 13). A significant improvement in median GRBAS score components was observed after calcium hydroxylapatite injection in terms of grade (p = 0.008), breathiness (p = 0.002) and aesthenia (p = 0.016). A pre- and post-procedural Voice Handicap Index was self-completed by 6 patients receiving calcium hydroxylapatite injection; the median change in score was an improvement of 19 points (interquartile range 36.5). CONCLUSION: We describe the outcomes of a comparatively large paediatric series and have found IML using calcium hydroxylapatite to be a reliable technique associated with improved subjective outcome measures. Management of UVCP in the child is a challenge with particular investigative and interventional considerations. Further study supported by high quality subjective and, where possible, objective outcome measures, is required to better inform patient selection, timing of intervention and choice of injection material.

Summary of the National Advisory Committee on Immunization (NACI) Statement on Seasonal Influenza Vaccine for 2016-2017.

BACKGROUND: Influenza is a respiratory infection caused primarily by influenza A and B viruses. Vaccination is the most effective way to prevent influenza and its complications. The National Advisory Committee on Immunization (NACI) provides recommendations regarding seasonal influenza vaccines annually to the Public Health Agency of Canada (the Agency). OBJECTIVE: To summarize the NACI recommendations regarding the use of seasonal influenza vaccines for the 2016-2017 influenza season. METHODS: Annual influenza vaccine recommendations are developed by NACI's Influenza Working Group for consideration and approval by NACI, based on NACI's evidence-based process for developing recommendations, and include a consideration of the burden of influenza illness and the target populations for vaccination; efficacy and effectiveness, immunogenicity and safety of influenza vaccines; vaccine schedules; and other aspects of influenza immunization. These recommendations are published annually on the Agency's website in the NACI Advisory Committee Statement: Canadian Immunization Guide Chapter on Influenza and Statement on Seasonal Influenza Vaccine (the Statement). RESULTS: The annual NACI seasonal influenza vaccine recommendations have been updated for the 2016-2017 influenza season to include adults with neurologic or neurodevelopment conditions among the groups for whom influenza vaccination is particularly recommended; to include the new high-dose, trivalent inactivated influenza vaccine for use in adults 65 years of age and over; to recommend that egg-allergic individuals may also be vaccinated against influenza using the low ovalbumin-containing live attenuated influenza vaccine (LAIV) licensed for use in Canada (NACI has previously recommended that egg-allergic individuals may be vaccinated using inactivated influenza vaccines); and to remove the preferential recommendation for the use of LAIV in children 2-17 years of age. Two addenda to the 2016-2017 Statement address these new LAIV recommendations. CONCLUSION: NACI continues to recommend annual influenza vaccination for all individuals aged six months and older, with particular focus on people at high risk of influenza-related complications or hospitalization, people capable of transmitting influenza to those at high risk and others as indicated.

The bowel cancer awareness campaign 'Be Clear on Cancer': sustained increased pressure on resources and over-accessed by higher social grades with no increase in cancer detected.

AIM: To evaluate the impact of the national 'Be Clear on Cancer' bowel cancer reminder campaign on service and diagnosis at a single UK institution. Secondly, to evaluate the socio-economic background of patients referred before and after the reminder campaign compared with the regional demographic. METHOD: Suspected cancer 2-week wait patients in the 3 months precampaign, postcampaign and after the reminder campaign were included. Demographics, investigations and diagnosis were recorded. The postcode was used to allocate a National Readership Survey social grade. RESULTS: Three hundred and eighty-three referrals were received in the 3 months precampaign, 550 postcampaign and 470 postreminder campaign. There were significant increases in the monthly referral rates following the campaign (P < 0.001 in both the post- and postreminder periods). Significantly more patients from social grades AB and C1C2 than expected from regional demographics were referred precampaign and after the reminder campaign (P < 0.001 in each case). There were no significant differences between the proportions of patients diagnosed with colorectal cancer in the three study periods (P = 0.710). CONCLUSION: The 'Be Clear on Cancer' bowel cancer campaign has had a significant sustained impact on resources. It has failed to increase referrals among lower socio-economic grades, leading to an increase in 'worried well' referrals and no change in numbers, or the stage, of colorectal cancers diagnosed.

An infant formula toxicity and toxicokinetic feeding study on carrageenan in preweaning piglets with special attention to the immune system and gastrointestinal tract.

A toxicity/toxicokinetic swine-adapted infant formula feeding study was conducted in Domestic Yorkshire Crossbred Swine from lactation day 3 for 28 consecutive days during the preweaning period at carrageenan concentrations of 0, 300, 1000 and 2250 ppm under GLP guidelines. This study extends the observations in newborn baboons (McGill et al., 1977) to piglets and evaluates additional parameters: organ weights, clinical chemistry, special gastrointestinal tract stains (toluidine blue, Periodic Acid-Schiff), plasma levels of carrageenan; and evaluation of potential immune system effects. Using validated methods, immunophenotyping of blood cell types (lymphocytes, monocytes, B cells, helper T cells, cytotoxic T cells, mature T cells), sandwich immunoassays for blood cytokine evaluations (IL-6, IL-8, IL1ß, TNF-α), and immunohistochemical staining of the gut for IL-8 and TNF-α were conducted. No treatment-related adverse effects at any carrageenan concentration were found on any parameter. Glucosuria in a few animals was not considered treatment-related. The high dose in this study, equivalent to ~430 mg/kg/day, provides an adequate margin of exposure for human infants, as affirmed by JECFA and supports the safe use of carrageenan for infants ages 0-12 weeks and older and infants with special medical needs.

Nasal dermoids in children: a proposal for a new classification based on 103 cases at Great Ormond Street Hospital.

OBJECTIVES: Nasal dermoids are rare developmental anomalies seen in children. This study reports the largest case series of 103 patients seen in a quaternary specialist unit over a 10-year period. We report the surgical and radiological findings and propose a new classification system, which clearly describes the extent of the lesions, thus allowing better surgical planning. METHODS: A retrospective review of case notes was conducted. Data collection included demographics, initial presentation, site of lesion, pre-operative CT and MRI imaging, surgical procedure, intraoperative findings (including depth of lesion), complications and recurrence. Surgical findings were correlated with radiological findings. RESULTS: A total of 103 patients were included in the study. The mean age at presentation was 29 months. 89% of children presented with a naso-glabellar or columellar lesion and 11% had a medial canthal lesion. All the patients underwent preoperative imaging and were treated with surgical excision. 58 children had superficial lesions, 45 had subcutaneous tracts extending to varying depths. Of these, 38 had intraosseous extension into the frontonasal bones, eight extended intracranially but remained extradural and two had intradural extension. There was good correlation between radiological and surgical findings. The superficial lesions were locally excised. The lesions with intraosseous tracts were removed via open rhinoplasty and the frontonasal bones drilled for access. Intracranial extension was approached either via a bicoronal flap and frontal craniotomy or the less invasive anterior small window craniotomy. CONCLUSIONS: This report describes the largest published cases series of nasal dermoids. The cases demonstrate the presenting features and the variable extent of the lesions. The new proposed classification; superficial, intraosseous, intracranial extradural and intracranial intradural, allows precise surgical planning. In the presence of intracranial extension, the low morbidity technique of using a brow incision and small window anterior craniotomy avoids the more invasive and commonly used bicoronal flap and frontal craniotomy.

Does a history of depression actually mediate smoking-related pain? Findings from a cross-sectional general population-based study.

BACKGROUND: Smokers report more pain and worse functioning. The evidence from pain clinics suggests that depression affects this relationship: The association between smoking and chronic pain is weakened when controlling for depression. This study explored the relationship between smoking, pain and depression in a large general population-based cohort (Generation Scotland: Scottish Family Health Study). METHODS: Chronic pain measures (intensity, disability), self-reported smoking status and a history of major depressive disorder (MDD) were analysed. A multivariate analysis of covariance determined whether smoking status was associated with both pain measures and a history of depressive illness. Using a statistical mediation model any mediating effect of depression on the relationship between smoking and chronic pain was sought. RESULTS: Of all 24,024 participants, 30% (n = 7162) reported any chronic pain. Within this chronic pain group, 16% (n = 1158) had a history of MDD; 7108 had valid smoking data: 20% (n = 1408) were current smokers, 33% (n = 2351) former and 47% (n = 3349) never smokers. Current smokers demonstrated higher pain intensity and pain-related disability scores compared with former and non-smokers (p < 0.001 for all analyses). From the mediation model, the effect on pain intensity decreased (p < 0.001), indicating that the relationship between smoking and a history of depression contributes significantly to the effect of smoking on pain intensity. When applied to smoking-related pain disability, there was no mediation effect. CONCLUSIONS: In contrast to smokers treated in pain clinics, a history of MDD mediated the relationship between smoking and pain intensity, but not pain-related disability in smokers in the community.

Peri-operative complications after adenotonsillectomy in a UK pediatric tertiary referral centre.

OBJECTIVES: Adenoidectomy and/or tonsillectomy are commonly performed in tertiary pediatric hospitals for the management of obstructive sleep apnea, often in children with significant comorbidities. This study examines the peri-operative course of a large series of complex patients undergoing such surgery at a major pediatric centre, reporting particularly cases of respiratory compromise requiring intensive care admission, both electively and unplanned. METHODS: This study was conducted by the pediatric ENT department at Great Ormond Street Hospital. All children undergoing adenoidectomy and/or tonsillectomy from July 2003 to December 2010 were included in this study. This involved a retrospective review of the case notes and hospital databases, with particular emphasis on those children requiring admission to the pediatric intensive care unit. RESULTS: A total of 1735 consecutive admissions for adenoidectomy and/or tonsillectomy (1627 individual patients aged 4-197 months, median 46 months) were included between 2003 and 2010 (998 adenotonsillectomies, 182 tonsillectomies and 555 adenoidectomies). In this group, 999/1627 patients (61.4%) had a diagnosis of sleep disordered breathing or sleep apnea, including 258 who had polysomnography. 407/1627 (25.0%) had no specific comorbidities which were felt likely to influence their surgical outcome. Established high risk factors included age less than 24 months (292), Down syndrome (99), neuromuscular problems (314), craniofacial abnormalities (94), storage diseases (23), morbid obesity (20), cardiovascular disease (133), respiratory disease (261), hemoglobinopathy (76) and coagulophathy (34). 300/1735 admissions were day cases and 1082/1735 were observed for one night. 353/1735 required more than one night in hospital (294 for two to three nights). 7/1735 had primary hemorrhage necessitating return to the operating room, all after tonsillectomy. 41/1735 (38 with major comorbidities) required peri-operative intensive care admission, mostly for respiratory support. Of these, 7 were admitted pre-operatively to intensive care, and 17 were planned post-operative transfers. Only 17/1735 required unanticipated post-operative admission to intensive care. Odds ratio analysis suggested a significantly higher chance of PICU admission in children with particular comorbidities (Down Syndrome, cardiac disease, obesity, cerebral palsy, craniofacial anomalies, mucopolysaccharidoses and hemoglobinopathy) when compared to children without comorbidities. Adenotonsillectomy was associated with a higher risk of PICU admission than adenoidectomy alone, but patient age less than 24 months was not associated with significantly higher rates of PICU admission. There were no peri-operative mortalities in this cohort. CONCLUSIONS: The peri-operative course was largely uneventful for the majority of children undergoing surgery during this period, particularly given the high prevalence of sleep apnea and other risk factors in this cohort. Major complications were uncommon, with 2.4% of these selected, typically high risk cases requiring peri-operative intensive care admission. Importantly, only 1% of all admissions required unanticipated transfer to intensive care. This has informed changes in peri-operative management in this unit, with implications for other pediatric tertiary referral centres.

MRI brain abnormalities in cochlear implant candidates: how common and how important are they?

OBJECTIVE: To investigate the incidence of abnormal findings on brain MRI in paediatric cochlear implantation candidates. METHODS: Retrospective review of brain MRI scans of cochlear implant patients between 2000 and 2009 who underwent MRI brain as part of their pre-operative work-up. RESULTS: MRI scans of 162 patients were reviewed (76 female patients and 86 male patients). The mean age at time of MRI scan was 3 years 8 months. Abnormalities were detected/ reported in 49 patients (30%). The total number of abnormalities detected was 51 (two patients had two separate abnormalities each). Of the abnormalities 82% could be related to known pre-existing conditions. 18% of the abnormalities were incidental/unexpected. Incidental/unexpected abnormalities were found in 9 patients (6%). Four of the patients with incidental abnormalities required referral and further investigations (2.5%). The most common abnormality detected was white matter changes (70%). All the white matter changes were related to pre-existing known medical conditions. CONCLUSION: At our institution abnormalities detected by pre-operative brain MRI scans on cochlear implant candidates are common (30%). The majority of abnormalities are related to known pre-existing medical conditions. Incidental findings are rare (4%) and approximately half of them required further investigation or referral.

Laryngotracheal reconstruction and cricotracheal resection in children: recent experience at Great Ormond Street Hospital.

BACKGROUND: Surgery for paediatric airway stenosis is constantly evolving. Surgery is the primary treatment modality via either an open or endoscopic approach. The objective of this study was to review the results of laryngotracheal reconstruction (LTR) and cricotracheal resection (CTR) procedures performed at Great Ormond Street Hospital over the past 10 years. METHODS: All patients who underwent open airway reconstruction surgery from January 2000 to December 2010 were included in this study. Patients treated entirely endoscopically were excluded. The data was collected using the electronic operating theatre database and the discharge summary database. RESULTS: Complete data was available for 199 patients who underwent open airway reconstruction from January 2000 to December 2010. The procedures included single stage LTR (57, 28.6%), two stage LTR (115, 57.7%), single-stage stomal reconstruction (14), single-stage CTR (8) and two-stage CTR (5). The diagnoses at the initial airway endoscopy were laryngeal web (22), subglottic stenosis (151), posterior glottic stenosis (9), suprastomal collapse (15), supraglottic stenosis (1) and tracheal stenosis (1). For those with subglottic stenosis, the stenosis was grade 1 in 1 patient, grade 2 in 26 patients, grade 3 in 117 patients and grade 4 in 6 patients. At the completion of intervention 175/199 (87.9%) patients reported improvement in their symptoms. Amongst the subglottic stenosis group, post LTR success was achieved in 100% with grade 1 stenosis, 92.3% with grade 2 stenosis, 88.1% in grade 3 stenosis and 83.3% in grade 4 stenosis. Of the two-stage LTR procedures, 100/115 (86.9%) had their tracheostomy removed and 15/115 (13.1%) have failed decannulation. Of the single-stage LTR group, 50/57 (87.7%) patients were better both on airway examination and symptomatically postoperatively. Of the single-stage stomal reconstruction group, 13/14 (92.8%) were better symptomatically and on airway examination. Patients who underwent single-stage CTR had a better airway on examination and were symptomatically improved in all cases (8/8). For the patients who underwent two stage CTR, the tracheostomy was removed in 3/5 (60%) and retained in 2/5 (40%). For the whole group, 15/199 (7.5%) patients underwent a revision LTR. On further analysis, revision LTR was required in 4/57 (7.1%) single-stage LTR, 9/115 (7.8%) two-stage LTR, 1/5 (20%) two-stage CTR and 1/8 (12.5%) single-stage CTR. In this study complications occurred in 13/199 (6.5%). CONCLUSIONS: Subglottic stenosis in children needs to be approached on the basis of the nature and severity of stenosis and the individual patient's general health. Good outcomes are achieved with both LTR and CTR. Good results are obtained both with single-stage and two-stage LTR, but restenosis remains a problem. An individual approach is required for treatment of paediatric airway stenosis to achieve good final outcomes. The overall success rate has increased only marginally in our institution over the last 20 years.

Branchial anomalies in children.

BACKGROUND: Branchial cleft anomalies are the second most common head and neck congenital lesions seen in children. Amongst the branchial cleft malformations, second cleft lesions account for 95% of the branchial anomalies. This article analyzes all the cases of branchial cleft anomalies operated on at Great Ormond Street Hospital over the past 10 years. METHODS: All children who underwent surgery for branchial cleft sinus or fistula from January 2000 to December 2010 were included in this study. RESULTS: In this series, we had 80 patients (38 female and 42 male). The age at the time of operation varied from 1 year to 14 years. Amongst this group, 15 patients had first branchial cleft anomaly, 62 had second branchial cleft anomaly and 3 had fourth branchial pouch anomaly. All the first cleft cases were operated on by a superficial parotidectomy approach with facial nerve identification. Complete excision was achieved in all these first cleft cases. In this series of first cleft anomalies, we had one complication (temporary marginal mandibular nerve weakness. In the 62 children with second branchial cleft anomalies, 50 were unilateral and 12 were bilateral. In the vast majority, the tract extended through the carotid bifurcation and extended up to pharyngeal constrictor muscles. Majority of these cases were operated on through an elliptical incision around the external opening. Complete excision was achieved in all second cleft cases except one who required a repeat excision. In this subgroup, we had two complications one patient developed a seroma and one had incomplete excision. The three patients with fourth pouch anomaly were treated with endoscopic assisted monopolar diathermy to the sinus opening with good outcome. CONCLUSION: Branchial anomalies are relatively common in children. There are three distinct types, first cleft, second cleft and fourth pouch anomaly. Correct diagnosis is essential to avoid inadequate surgery and multiple procedures. The surgical approach needs to be tailored to the type of anomaly of origin of the anomaly. Complete excision is essential for good outcomes.

Measuring the accuracy of different ways to identify the 'at-risk' foot in routine clinical practice.

AIMS: We aimed to identify which individual risk factors best predict foot ulceration in routine clinical practice and whether an integrated clinical tool is a better screening tool for future foot ulceration. METHODS: Routinely collected clinical information on foot and general diabetes indicators were recorded on the regional diabetes electronic register. Follow-up data on foot ulceration were collected from the same electronic record, the local multidisciplinary foot clinic and community and hospital podiatry paper records. Data were electronically linked to see which criteria best predicted future foot ulceration. RESULTS: Foot risk scores were recorded on 3719 patients (44% female, mean age 59±15years) across community and hospital clinics. Overall, 851 (22.9%) had insensitivity to monofilaments, in 629 (17.2%) both pulses were absent and 184 (4.9%) had a prior ulcer. In multivariate analysis, the strongest predictors of foot ulceration were prior ulcer, insulin treatment, absent monofilaments, structural abnormality and proteinuria and retinopathy. The sensitivity of predicting foot ulceration was 52% for prior ulcer, 61% for absent monofilaments, 75% for 'high risk' on an integrated risk score and 91% for high and moderate risk combined. The corresponding specificities were 99, 81, 89 and 61%. Positive likelihood ratio was 52 for prior ulcer and 6.8 for foot risk, with negative likelihood ratios of 0.48 and 0.15, respectively. CONCLUSIONS: Integrated foot risk scores are more sensitive than individual clinical criteria in predicting future foot ulceration and are likely to be better screening tools, where excluding false negative results is of paramount importance.

Increased BDNF levels and NTRK2 gene association suggest a disruption of BDNF/TrkB signaling in autism.

The brain-derived neurotrophic factor (BDNF), a neurotrophin fundamental for brain development and function, has previously been implicated in autism. In this study, the levels of BDNF in platelet-rich plasma were compared between autistic and control children, and the role of two genetic factors that might regulate this neurotrophin and contribute to autism etiology, BDNF and NTRK2, was examined. We found that BDNF levels in autistic children (n = 146) were significantly higher (t = 6.82; P < 0.0001) than in control children (n = 50) and were positively correlated with platelet serotonin distribution (r = 0.22; P = 0.004). Heritability of BDNF was estimated at 30% and therefore candidate genes BDNF and NTRK2 were tested for association with BDNF level distribution in this sample, and with autism in 469 trio families. Genetic association analysis provided no evidence for BDNF or NTRK2 as major determinants of the abnormally increased BDNF levels in autistic children. A significant association with autism was uncovered for six single nucleotide polymorphisms (SNPs) [0.004 (Z((1df)) = 2.85) < P < 0.039 (Z((1df)) = 2.06)] and multiple haplotypes [5 × 10(-4) (χ((3df)) = 17.77) < P < 0.042 (χ((9df)) = 17.450)] in the NTRK2 gene. These results do not withstand correction for multiple comparisons, however, reflect a trend toward association that supports a role of NTRK2 as a susceptibility factor for the disorder. Genetic variation in the BDNF gene had no impact on autism risk. By substantiating the previously observed increase in BDNF levels in autistic children in a larger patient set, and suggesting a genetic association between NTRK2 and autism, this study integrates evidence from multiple levels supporting the hypothesis that alterations in BDNF/tyrosine kinase B (TrkB) signaling contribute to an increased vulnerability to autism.

Parotid duct ligation for treatment of drooling in children with neurological impairment.

OBJECTIVE: Multiple surgical procedures have been advocated for the management of problematic drooling in neurologically impaired children. Parotid duct ligation is a quick and simple operation conducted via an intra-oral approach and usually performed simultaneously with other procedures. In this study, we aimed to evaluate the effectiveness of parotid duct ligation as a discrete procedure. METHODS: All children who underwent bilateral parotid duct ligation as the solitary operative intervention at that time, between February 2003 and September 2006, were included in the study. RESULTS: Ten children were studied. Surgery was successful in 80 per cent of cases. One patient (10 per cent) had a post-operative wound infection. CONCLUSIONS: Bilateral parotid duct ligation is an effective yet conservative operation for drooling in neurologically impaired children. It requires minimal surgical dissection and has a low morbidity rate. It should be considered as a potential first-line procedure in children who aspirate, and as a further surgical option in anterior droolers or those who continue to drool unacceptably following prior surgical intervention.