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Adaptive clinical trial designs offer significant opportunities to optimize the conduct of clinical trials for the benefit of the subjects in the trial, the subjects that may be treated after the trial and the trial sponsor. However currently, the use of adaptive designs is limited, due to statistical, regulatory and logistical concerns. In this article we share our experience of overcoming the last of these over a range of phase 2, response adaptive, dose finding studies. Based on our experience we feel quite strongly that the logistics of executing adaptive trials should not be a barrier to their use., (Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.)

Signal transducer and activator of transcription (STAT) proteins are transcription factors that play a critical role in the response of a variety of eukaryotic cells to cytokine and growth factor signaling. In Drosophila, the STAT homolog encoded by the stat92E gene is required for the normal development of multiple tissues, including embryonic segmentation, imaginal discs, blood cells, male germ cells, and sex determination. We used multiple approaches to study the role of stat92E in oogenesis. Stat92E RNA expression is strongest in the differentiating follicle cells in the germarium, as determined by in situ hybridization. We generated an ethylmethane sulfonate-induced, temperature-sensitive allele, stat92E(F), in which the mutant protein contains a P506S substitution, located in the DNA binding domain. At the restrictive temperature, mutant females are sterile. Mutant ovaries have multiple defects, including fused egg chambers and an absence of interfollicular stalks cells and functional polar follicle cells. An analysis of mosaic clones, using an apparent null stat92E allele, indicates that Stat92E is required in the polar/stalk follicle cell lineage. We conclude that stat92E is necessary for the early differentiation of follicle cells and for proper germ line cell encapsulation during Drosophila oogenesis., ((C)2002 Elsevier Science (USA).)

Jak kinases are critical signaling components in hematopoiesis. While a large number of studies have been conducted on the roles of Jak kinases in the hematopoietic cells, much less is known about the requirements for these tyrosine kinases in other tissues. We have used loss of function mutations in the Drosophila Jak kinase Hopscotch (Hop) to determine the role of Hop in eye development. We find that Hop is required for cell proliferation/survival in the eye imaginal disc, for the differentiation of photoreceptor cells, and for the establishment of the equator and of ommatidial polarity. These results indicate that hop activity is required for multiple developmental processes in the eye, both cell-autonomously and nonautonomously., (Copyright 1999 Academic Press.)

Objectives: We hypothesised that, in the subgroup of seriously injured patients who receive early critical care in the operating theatre or intensive care unit, there would be a greater actual survival rate than that statistically predicted using trauma scoring techniques., Methods: 1031 seriously injured patients on a national trauma database were analysed. The numbers of survivors in 3 initial destination groups [intensive care unit (ICU), theatre and ward] were compared with the average number of survivors statistically predicted for similar groups of patients using the TRISS methodology. W statistics were then used to test for statistical significance., Results: 77/122 patients admitted to an ICU survived (predicted number 66, W stat 8.8 [2.6-15.0]). 129/178 patients transferred to theatre survived (predicted number 113, W stat 8.8 [4.2-13.5]). 296/348 patients admitted to a ward survived (predicted number 292, W stat 1.3 [-1.9-4.4])., Conclusions: The number of patients who survive after severe injury is significantly greater than the number predicted to survive by current trauma scoring methods if the patient is sent directly to theatre or are admitted directly to the ICU. Survival is as predicted if the patient is sent initially to a ward.

Percutaneous dilatation tracheostomy has become a common procedure for bedside insertion of tracheostomy tubes in the intensive care unit. Management of the airway during the procedure using the laryngeal mask airway (LMA) and other methods has been described. The intubating laryngeal mask airway has several potential benefits for airway management during percutaneous dilatation tracheostomy compared with the LMA. These include the use of both the fibreoptic bronchoscope and tracheal tube if necessary. We report the results of a pilot study of 10 patients that illustrates these advantages.

Study Objective: To determine the efficacy and speed of onset of analgesia of a single dose of intravenous (IV) or intramuscular (IM) ketorolac tromethamine following major orthopedic surgery., Study Design: Double-blind, randomized, placebo-controlled trial., Setting: A district general hospital in England., Patients: 112 patients aged 18 to 80 years suffering moderate or severe pain following orthopedic surgery., Interventions: Patients were randomized to receive 30 mg ketorolac IV, 30 mg ketorolac IM, or placebo following surgery., Measurements and Main Results: Verbal pain intensity scores were performed prior to admission to the study, then frequently for the first 45 minutes following administration of study medication, and subsequently at hourly intervals. Times to request for further analgesia were noted. Patient assessment of overall acceptability and pain relief of the study medication was recorded. There was no statistical difference in speed of onset of analgesia between the ketorolac groups and placebo. Median (range) times to first analgesic following study drugs were: ketorolac IV 45 minutes (9 to 1440 minutes), ketorolac IM 34 minutes (10 to 1440 minutes), placebo 24 minutes (10 to 615 minutes). There was a statistically significant difference between the ketorolac groups and placebo (ketorolac IV vs. placebo, p < 0.01; ketorolac IM vs. placebo, p = 0.03). Patient assessment of overall acceptability and pain relief was significantly better for IV ketorolac compared with placebo (p < 0.01). By 6 hours, 78% of the IV ketorolac group and 95% of the IM ketorolac and placebo groups required further analgesia., Conclusions: Despite high patient acceptability compared with placebo, the use of ketorolac as the sole analgesic failed to control postoperative pain following major orthopedic surgery. IV administration of ketorolac conferred no advantages over the IM route with regard to efficacy or speed of onset.

Continuous postoperative nocturnal pulse oximetry was performed in 20 patients undergoing elective cholecystectomy to examine if the composition of anaesthetic gas mixtures affects postoperative gas exchange. The patients were allocated randomly to receive either nitrogen or nitrous oxide during anaesthesia, and oximetry was performed on the night before operation and the first and third nights after operation. Considerable oxygen desaturation was seen in both groups. During the first night after operation the proportion of the night during which oxygen saturation was less than 85% was greater in the nitrogen group than in the nitrous oxide group, but there was no significant difference between the mean overnight saturation values of the two groups.