Development and usability of a new subcutaneous auto-injector device to administer hydroxyprogesterone caproate to reduce the risk of recurrent preterm birth

Michael N Travanty,1 Bryon Calawa,2 Waleed S Shalaby,3 Michael J Jozwiakowski,3 Kyle B Haraldsen4 1Product Development, Antares Pharma, Minneapolis, MN, USA; 2Research Department, Design Science, Philadelphia, PA, USA; 3Medical Affairs, AMAG Pharmaceuticals, Inc., Waltham, MA, USA; 4Technical Operations & Project Management, AMAG Pharmaceuticals, Inc., Waltham, MA, USA Background: Current administration of hydroxyprogesterone caproate (HPC) by intramuscular injection is associated with limitations, including the potential for human error and contamination, patient anxiety, and increased risk of needlestick injury. Objective: To describe the design of an auto-injector for subcutaneous (SC) administration of HPC and the results of studies that evaluated the target user’s understanding of the proper use of this device. Materials and methods: A single-use, prefilled, fixed-dose, disposable auto-injector intended for the SC administration of HPC was developed, and its usability by health care providers was evaluated in 3 formative (N=32, 64 injections) and 3 validation studies (N=45, 90 injections). These studies consisted of one-on-one testing sessions performed in a simulated home environment. Analyses were based on observed use error or use difficulty during the performance of specific tasks, including those considered critical (associated with high severity harms). Results: In the formative studies, the majority of participants correctly administered an injection with the auto-injector, but prior training improved performance. Specific errors were noted, including holding the device at the injection site for a period inconsistent with its instructions for use (IFU). The IFU was modified to reduce potential occurrence of these errors. Use errors were subsequently observed on critical tasks in the first and second validation studies, including hold-time errors that were attributed to using visual cues rather than counting seconds. For the third validation study, the IFU was modified to focus on visual cues and all users were able to successfully perform the injection per the IFU. Conclusion: An auto-injector device for SC administration of HPC for reduction in risk of recurrent preterm birth was successfully developed through iterative design and validation testing. The device design provides high usability and acceptance of this device by health care professionals. Keywords: hydroxyprogesterone caproate, 17P, auto-injector, subcutaneous injection, usability, human factors, combination devic

History and evolution of the arctic flora: in the footsteps of Eric Hultén

A major contribution to our initial understanding of the origin, history and biogeography of the present-day arctic flora was made by Eric Hulten in his landmark book Outline of the History of Arctic and Boreal Biota during the Quarternary Period, published in 1937. Here we review recent molecular and fossil evidence that has tested some of Hulten's proposals. There is now excellent fossil, molecular and phytogeographical evidence to support Hulten's proposal that Beringia was a major northern refugium for arctic plants throughout the Quaternary. In contrast, most molecular evidence fails to support his proposal that contemporary east and west Atlantic populations of circumarctic and amphi-Atlantic species have been separated throughout the Quaternary. In fact, populations of these species from opposite sides of the Atlantic are normally genetically very similar, thus the North Atlantic does not appear to have been a strong barrier to their dispersal during the Quaternary. Hulten made no detailed proposals on mechanisms of speciation in the Arctic; however, molecular studies have confirmed that many arctic plants are allopolyploid, and some of them most probably originated during the Holocene. Recurrent formation of polyploids from differentiated diploid or more low-ploid populations provides one explanation for the intriguing taxonomic complexity of the arctic flora, also noted by Hulten. In addition, population fragmentation during glacial periods may have lead to the formation of new sibling species at the diploid level. Despite the progress made since Hulten wrote his book, there remain large gaps in our knowledge of the history of the arctic flora, especially about the origins of the founding stocks of this flora which first appeared in the Arctic at the end of the Pliocene (approximately 3 Ma). Comprehensive analyses of the molecular phylogeography of arctic taxa and their relatives together with detailed fossil studies are required to fill these gaps.</p

Response of alpine plant florwer production to temperature and snow cover fluctuation at the species range boundary

Surface temperatures have risen globally during the last 30 years, especially in alpine areas. It is recognized that these increases are influencing phenology, physiology and distribution of plants. However, few studies have addressed the effects of climate warming at the species range boundary, where plants are expected to be more stressed. We analysed 11-year data sets of inflorescence production of four alpine plants (Carex foetida, Leucanthemopsis alpina, Senecio incanus, Silene suecica) at the southern boundary of their distribution range in the N-Apennines (N-Italy), in relation to air temperature and snow cover persistence. Inflorescence production of all species fluctuated greatly and was significantly affected by the variation of the mean temperature of June/July. We found significant relationships also between species data series and the snow cover persistence. Moreover, species responded differently to such parameters. One species showed a significant decrease of the reproductive effort, whereas the other three showed a stable trend of inflorescence production. We have shown that some alpine species are favoured by increased temperature and reduced snow cover even at the boundary of their range, where they are thought to be particularly sensitive to warming. However, the aptitude to cope with climate change might be limited by competition against thermophilous species migrating from lower altitude and in some cases by the low altitude of mountain peaks that prevent species upward migration. The individualistic response of species to climate change found here, support the statement that the composition of plant communities might rapidly change in the future. © 2011 Springer Science+Business Media B.V