Endpoint comparison for bone mineral density measurements in North Central Cancer Treatment Group cancer clinical trials N02C1 and N03CC (Alliance).

UNLABELLED: Bone mineral density (BMD) measurement can vary depending upon anatomical site, machine, and normative values used. This analysis compared different BMD endpoints in two clinical trials. Trial results differed across endpoints. Future clinical trials should consider inclusion of multiple endpoints in sensitivity analysis to ensure sound overall study conclusions. INTRODUCTION: Methodological issues hamper efficacy assessment of osteoporosis prevention agents in cancer survivors. Osteoporosis diagnosis can vary depending upon which bone mineral density (BMD) anatomical site and machine is used and which set of normative values are applied. This analysis compared different endpoints for osteoporosis treatment efficacy assessment in two clinical studies. METHODS: Data from North Central Cancer Treatment Group phase III clinical trials N02C1 and N03CC (Alliance) were employed involving 774 patients each comparing two treatments for osteoporosis prevention. Endpoints for three anatomical sites included raw BMD score (RawBMD); raw machine-based, sample-standardized, and reference population-standardized T scores (RawT, TSamp, TRef); and standard normal percentile corresponding to the reference population-standardized T score (TPerc). For each, treatment arm comparison was carried out using three statistical tests using change and percentage change from baseline (CB, %CB) at 1 year. RESULTS: Baseline correlations among endpoints ranged from 0.79 to 1.00. RawBMD and TPerc produced more statistically significant results (14 and 19 each out of 36 tests) compared to RawT (11/36), TSamp (8/36), and TRef (7/36). Spine produced the most statistically significant results (26/60) relative to femoral neck (20/60) and total hip (13/60). Lastly, CB resulted in 44 statistically significant results out of 90 tests, whereas %CB resulted in only 15 significant results. CONCLUSIONS: Treatment comparisons and interpretations were different across endpoints and anatomical sites. Transforming via sample statistics provided similar results as transforming via reference or machine-based norms. However, RawBMD and TPerc may be more sensitive to change as clinical trial endpoints.

Geological record and reconstruction of the late Pliocene impact of the Eltanin asteroid in the Southern Ocean.

In 1995, an expedition on board the research vessel FS Polarstern explored the impact site of the Eltanin asteroid in the Southern Ocean, the only known asteroid impact into a deep ocean basin. Analyses of the geological record of the impact region place the event in the late Pliocene (approximately 2.15 Myr) and constrain the size of the asteroid to be >1 km. The explosive force inferred for this event places it at the threshold of impacts believed to have global consequences, and its study should therefore provide a baseline for the reconstruction and modelling of similar events, which are common on geological timescales.

[Morphometric studies on lymphatic vessels of the axillary region]. / Morphometrische Untersuchungen an Lymphgefässen des Axillarbereiches.

Axillary lymph vessels of 94 autopsy cases (42 female, 52 male) have been investigated histologically in serial slices. Total diameter of the lymph vessels, vascular wall diameter, diameter of the medial connective tissue, finally that one of the artificial tissue spaces were measured in almost 8000 single measurements. The mean values of counts for the different vascular wall components were assessed statistically with the aid of a computer. By reason of the enormous individual variation of the number and the size in lymph vessel system a direct comparison of the measurement data from the different wall components was impossible. Therefore, the ratio of connective tissue to smooth muscle within the vascular media was regarded as a significant parameter for the development of a lymphangiosclerosis. The connective tissue/smooth muscle gradient increased from decade to decade with a slighter progression in groups with higher age A significant increase of lymphangi osclerosis was noted in cases with right heart insufficiency in correlation to the degree of heart insuffiency. Severe lymphangiosclerotic alterations were developed after radical mastectomy and radiotherapy of the axilla, after radiotherapy of other malignant tumors, and in cases with heart failures or vascular dysplasia. Morphometric investigations were not possible in cases with floride lymphangitis and in one case of general vascular amyloidosis.