Which treatment for low back pain? A factorial randomised controlled trial comparing intravenous analgesics with oral analgesics in the emergency department and a centrally acting muscle relaxant with placebo over three days [ISRCTN09719705]

BACKGROUND: About two thirds of adults suffer from backpain at some time during their life. In the emergency room many patients with acute back pain are treated with intravenous non-steroidal analgesics. Whether this treatment is superior to oral administration of non-steroidal analgesics is unknown. Intravenous administration, however, requires considerable amounts of resources and accounts for high workload in busy clinics. In the further course centrally acting muscle relaxants are prescribed but the effectiveness remains unclear. The objective of this study is on the one hand to compare the effectiveness of intravenous with oral non-steroidal analgesics for acute treatment and on the other hand to compare the effectiveness of a centrally active muscle relaxant with placebo given for three days after presentation to the ED (emergency department). METHODS/DESIGN: This study is intended as a randomised controlled factorial trial mainly for two reasons: (1) the sequence of treatments resembles the actual proceedings in every-day clinical practice, which is important for the generalisability of the results and (2) this design allows to take interactions between the two sequential treatment strategies into account. There is a patient preference arm included because patients preference is an important issue providing valuable information: (1) it allows to assess the interaction between desired treatment and outcome, (2) results can be extrapolated to a wider group while (3) conserving the advantages of a fully randomised controlled trial. CONCLUSION: We hope to shed more light on the effectiveness of treatment modalities available for acute low back pain

The standardisation of i and y in Early Modern English (1500-1700)

Between the sixteenth and the seventeenth century, i and y shifted from an early distribution principle to a new, modern standard, which generally resulted in the establishment of vocalic word-initially and word-medially, as well as for glides word-initially and for vowels word-finally. Previous scholars have offered interesting insights into some of the graphemes above, but the overall history of development in i and y, and the factors behind their modern standardisation, still remain partially uncovered. This paper investigates graphemic changes in the two letters in printed English between 1500 and 1700, using a quantitative model for the analysis of patterns across a range of texts from Early English Books Online. The analysis establishes the presence of a quantitative shift in the wholesale uses of and between the sixteenth and the seventeenth centuries, and provides a precise chronology for the standardisation of word-initial, word-medial and word-final graphemic changes in i and y. The discussion reflects upon the development of the positional graphemes, and argues for pragmatic factors within the Early Modern English printing industry as primarily responsible for the modern standardisation of i and y