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Aim: To evaluate the the understanding, proficiency, confidence with and anticipated usefulness of common airway assessment techniques when assessing patients for provision of conscious sedation amongst dental sedationists. Methods: An online questionnaire was sent to conscious sedation providers in dentistry in the UK. The questionnaire explored current practice, use and documentation of airway assessment and information regarding airway-related complications experienced. Results: 254 responses were received. 67% routinely carried out airway assessment whilst 40% documented this finding most or all the time. The average number of airway assessment techniques known was 3.96 of 8. The most common technique known was measurement of mouth opening (71%); this was the most used, the technique participants were most confident using, and the technique found to be the most useful. 11 % had experienced an incident where obstruction or hypoxia had occurred where an airway assessment could have predicted this. Conclusions: The need for airway assessment is recognised within current guidelines and this study illustrates dentists do routinely carry out airway assessment. The technique used, documentation and level of training are varied. A uniform approach to training and the use of a formalised tool may help improve application of airway assessment in sedation in dentistry. [ABSTRACT FROM AUTHOR]

Michael Gillen,1 Shakti Valdez,2 Dongmei Zhou,2 Bradley Kerr,2 Caroline A Lee,2 Zancong Shen2 1AstraZeneca LP, Gaithersburg, MD, 2Ardea Biosciences, Inc., San Diego, CA, USA Introduction: Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI) in patients who have not achieved target serum uric acid (sUA) levels with an XOI alone. Most people with gout have chronic kidney disease. The pharmacokinetics, pharmacodynamics, and safety of lesinurad were assessed in subjects with impaired renal function. Methods: Two Phase I, multicenter, open-label, single-dose studies enrolled subjects with normal renal function (estimated creatinine clearance [eCrCl] >90 mL/min; N=12) or mild (eCrCl 60–89 mL/min; N=8), moderate (eCrCl 30–59 mL/min; N=16), or severe (eCrCl

Zancong Shen,1 Michael Gillen,2 Kathy Tieu,1 Mai Nguyen,1 Erin Harmon,1 David M Wilson,1 Bradley Kerr,1 Caroline A Lee1 1Ardea Biosciences, Inc., San Diego, CA, 2AstraZeneca LP, Gaithersburg, MD, USA Introduction: Lesinurad is a selective uric acid reabsorption inhibitor approved in the United States and Europe for treatment of gout in combination with a xanthine oxidase inhibitor. A maximum tolerated dose study was conducted to determine the lesinurad supratherapeutic dose, followed by a thorough QTc study to characterize the effect of lesinurad on cardiac repolarization.Methods: The maximum tolerated dose study was a randomized, double-blind, placebo-controlled, single-ascending dose study that enrolled 35 healthy men and women. Lesinurad plasma exposure (maximum observed plasma concentration and area under the plasma concentration versus time curve) was determined at doses of 800 mg, 1,200 mg, and 1,600 mg. The thorough QTc study was a double-blind, four-period, placebo-controlled crossover study with 54 healthy men and women who received single doses of lesinurad 1,600 mg (supratherapeutic dose), lesinurad 400 mg, moxifloxacin 400 mg, and placebo in randomized sequence. Digital 12-lead electrocardiograms were recorded at eleven time points over 24 hours in each treatment period. QT intervals were corrected for heart rate using an individual-specific correction factor (QTcI).Results: The upper bound of the one-sided 95% confidence interval for time-matched, placebo-subtracted, baseline-adjusted QTcI intervals (ΔΔQTcI) was 480 ms or QTcI increases >30 ms were observed. Moxifloxacin mean QTcI intervals were >5 ms, and the lower bounds of the 90% confidence interval were >5 ms at 2 hours, 3 hours, and 4 hours, confirming assay sensitivity.Conclusion: Lesinurad, at supratherapeutic doses, does not have a significant effect on the QT interval in healthy male or female subjects. Keywords: pharmacokinetics, maximum tolerated dose study, QT interval, selective uric acid reabsorption inhibitor

Zancong Shen, Colin Rowlings, Brad Kerr, Vijay Hingorani, Kimberly Manhard, Barry Quart, Li-Tain Yeh, Chris Storgard Ardea Biosciences, Inc. (a member of the AstraZeneca group), San Diego, CA, USA Abstract: Lesinurad is a selective uric acid reabsorption inhibitor under investigation for the treatment of gout. Single and multiple ascending dose studies were conducted to evaluate pharmacokinetics, pharmacodynamics, and safety of lesinurad in healthy males. Lesinurad was administered as an oral solution between 5 mg and 600 mg (single ascending dose; N=34) and as an oral solution or immediate-release capsules once daily (qday) between 100 mg and 400 mg for 10 days under fasted or fed condition (multiple ascending dose; N=32). Following single doses of lesinurad solution, absorption was rapid and exposure (maximum observed plasma concentration and area under the plasma concentration–time curve) increased in a dose-proportional manner. Following multiple qday doses, there was no apparent accumulation of lesinurad. Urinary excretion of unchanged lesinurad was generally between 30% and 40% of dose. Increases in urinary excretion of uric acid and reductions in serum uric acid correlated with dose. Following 400 mg qday dosing, serum uric acid reduction was 35% at 24 hours post-dose, supporting qday dosing. A relative bioavailability study in healthy males (N=8) indicated a nearly identical pharmacokinetic profile following dosing of tablets or capsules. Lesinurad was generally safe and well tolerated. Keywords: urinary excretion, urate lowering, URAT1, single and multiple doses, food effect, clearance

The article describes the identification of six different point mutations (P35A, P35S, A36P, E48K, R167G, and P187S) in the bone morphogenetic protein (BMP) antagonist NOGGIN (NOG).

A Study provides molecular evidence implicating the role of a specific 3-bp inframe deletion of the neurofibromatosis type 1 (NF1) gene in the determination of a clinical phenotype such as development of cutaneous, subcutaneous and superficial plexiform neurofibromas. Molecular analysis led to the identification of the same 3-bp inframe deletion (c.2970-2972 delAAT) in exon 17 of the NF1 gene in all affected subjects.

Aims: To compare the natural history of sporadic optic glioma with those associated with neurofibromatosis type 1 (NF1 ). Methods: Optic glioma cases were identified using both the Manchester Children's [...]