An informatics strategy to assure enrollment criteria compliance in studies of the critically ill

Up to 18% of acutely ill patients randomized into multicenter clinical trials may not satisfy inclusion/exclusion criteria. To improve compliance with such criteria in an ICU-based multicenter international drug trial, we established a novel Internet/telephone-based strategy for providing rapid case approval or disapproval by centralized panels of critical care physicians. We assessed whether these panels could acquire and record accurate patient information, and whether this approach would minimize enrollment of ineligible patients and could be accomplished in a timely fashion. Analysis of the first 1000 submitted patients showed accurate data capture for 98.7% of enrolled and randomized patients. Median response time from case submission to panel member decision was 34.7 min. Over 99% of enrolled patients met critical study criteria. We conclude that, an Internet-based communications strategy appears to be a valuable adjunct to multicenter clinical trials in acutely ill patients when rapid assurance of eligibility is required.     

Effect of three radicular dentine treatments and two luting cements on the regional bond strength of quartz fibre posts

The purpose was to investigate by push-out tests and scanning electron microscopy (SEM)/energy-dispersive spectroscopy (EDS) the effect, after first acid etching the post space walls, of three radicular dentine treatments on the regional bond strength of quartz fibre posts placed using two heavily filled resin luting cements. The crowns of 39 extracted maxillary central incisors were sectioned transversely 2 mm coronal to the labial cement-enamel junction and the roots endodontically treated. After standardized post space preparations and etching 15 s with 32% phosphoric acid, 36 roots were randomly divided into six equal groups. Quartz fibre posts (D.T. LIGHT-POST) were placed using three radicular dentine treatments (0.9% sodium chloride (NaCl) for 60 s, 10% sodium hypochlorite (NaOCl) for 60 s, 17% ethylenediaminetetraacetic acid (EDTA) for 60 s followed by 5.25% NaOCl for 60 s) and two resin composite luting cements (ONE-STEP PLUS/DUO-LINK; ONE-STEP PLUS/LuxaCore Dual). Transverse segments (S1–S7), 1.00 mm (SD = 0.05 mm) thick, were sectioned from the coronal 8 mm of each root. Push-out bond strength tests were performed on coronal, middle and apical post space segments (S2, S4, S6) at a crosshead speed of 0.5 mm/min. Data were recorded and analyzed using a two-way mixed ANOVA design (a = 0.05). Three segments (S1, S5, S7) from roots in each group were examined using SEM/EDS. After post space preparation, acid etching and using each of the three radicular dentine treatments, the three remaining roots were sectioned longitudinally for SEM observation of the post space walls. At all root segment sites, the mean bond strengths from using 0.9% NaCl were significantly lower than for the other two radicular dentine treatments (P ≤ 0.02), and DUO-LINK cement had significantly higher mean bond strengths than LuxaCore Dual cement (P ≤ 0.01). There was a significant linear trend for reduced bond strengths from coronal to apical post space segments (P < 0.001), which was supported by the SEM/EDS observations of dentine tubule appearance and resin tag formation. Acid etching followed by either 10% NaOCl or 17% EDTA and 5.25% NaOCl dentine treatments of the post spaces provided good adhesion and resin luting cement tag infiltration of dentinal tubules in the coronal and middle segments in particular.     

Design and synthesis of deuterated boceprevir analogs with enhanced pharmacokinetic properties

As part of an ongoing effort to apply the Deuterated Chemical Entity Platform (DCE Platform?) to clinically validated drugs, the synthesis of deuterated analogs of the hepatitis C virus protease inhibitor boceprevir was carried out. The devised synthetic routes allowed for site‐selective deuterium incorporation with high levels of isotopic purity. Application of the DCE Platform? to boceprevir enabled the identification of several deuterated analogs that display marked levels of in vitro metabolic stabilization. Most notably, analog 1g exhibits a near doubling of in vitro half‐life in human liver microsomal assays. The details of the convergent synthetic route to the boceprevir isotopologs and the results of the metabolic stability assays are described herein.