Using negative control outcomes to assess the comparability of treatment groups among women with osteoporosis in the United States

Purpose: In contrast to randomized clinical trials, comparative safety and effectiveness assessments of osteoporosis medications in clinical practice may be subject to confounding by indication. We used negative control outcomes to detect residual confounding when comparing osteoporosis medications. Methods: Using MarketScan Commercial and Supplemental claims, we identified women aged ≥55 years who initiated an oral bisphosphonate (BP) (risedronate, alendronate, or ibandronate), denosumab (an injected biologic), or intravenous zoledronic acid (ZA) from October 1, 2010 to September 30, 2015. Women with Paget's disease or cancer were excluded. We compared individual oral BPs to each other, denosumab to ZA, denosumab to oral BPs, and ZA to oral BPs, with respect to 11 negative control outcomes identified by subject matter experts. We estimated the 12-month cumulative risk difference (RD) using inverse probability of treatment and censoring weights. Results: Among 148 587 women, most initiated alendronate (57%), followed by ibandronate (12%), ZA (11%), risedronate (10%), and denosumab (10%). Compared with denosumab, patients initiating ZA had similar risks of all negative control outcomes. Compared with oral BPs, patients initiating denosumab had a higher risk of a wellness visit (RD = 1.2%, 95% CI: 0.4, 1.9) and a lower risk of receiving herpes zoster vaccine (RD = −0.6%, 95% CI: −1.1, −0.2). Comparing ZA with oral BP initiators resulted in two outcomes with positive associations. Conclusions: Caution is warranted when comparing injectable vs oral osteoporosis medications, given the potential for unmeasured confounding. Evaluating negative control outcomes could be a standard validity check prior to conducting comparative studies

A systematic survey of floral nectaries

The construction of classifications, as well as the understanding of biological diversity, depends upon a careful comparison of attributes of the organisms studied (Stuessy, 1990). It is widely known that data from diverse sources showing differences from taxon to taxon are of systematic significance. Dur-ing the 20th century, systematists have emphasized that their discipline involves a synthesis of all knowledge (Stevens, 1994) or, in other words, the variation of as many relevant characters as possible should be incorporated into the natural system to be constructed. The extent to which particular characters are constant or labile will determine their usefulness to syste-matics. In general, more conservative characters will be valuable in defining families and orders, whereas more labile characters may be useful at the ge-neric and specific levels (Webb, 1984). There is no doubt that floral characters are among the most used in the classification of flowering plants. At the same time, they constitute essential features in diagnostic keys to taxa in both taxonomic treatments and Floras (Cronquist, 1981, 1988).Fil: Bernardello, Gabriel Luis Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentin