Fracture rate associated with quality metric-based anti-osteoporosis treatment in glucocorticoid-induced osteoporosis.

UNLABELLED: Anti-osteoporosis medication (AOM) use in patients exposed to glucocorticoids is thought to reduce fractures. We found post-menopausal women using glucocorticoids for at least 90 days who also used an AOM within 90 days had 48 % fewer fractures by 1 year and 32 % fewer fractures by 3 years compared to non-AOM users. INTRODUCTION: The purpose of this study is to explore the effectiveness of adherence to quality measures by estimating the effect of anti-osteoporosis medication (AOM) initiation within 90 days after chronic (≥90 days) glucocorticoid (GC) therapy on osteoporotic fracture. METHODS: A new-user cohort was assembled using the MarketScan databases between 2000 and 2012. Included patients were female, age ≥50 at GC initiation, had a first GC fill daily dose ≥10 mg and persisted for at least 90 days. During a 365-day baseline period, patients were excluded for prior GC or AOM (bisphosphonate, denosumab, teriparatide) use, fracture, or cancer diagnosis. Initiators of an AOM in the 14 days pre- or 90 days post-GC fill were characterized as AOM users; those without, AOM non-users. Follow-up began 91 days after GC fill with patients followed until fracture, loss of continuous enrollment, initiation of AOM by AOM non-users, or end of study period. A propensity score was estimated for AOM receipt using all measured covariates and converted to a stabilized inverse probability of treatment weights (IPTW). Weighted hazard ratios (HR) and associated 95% confidence intervals (95% CI) were estimated using weighted Cox proportional hazard models. RESULTS: Of the 7885 women eligible for the study, 12.1% were AOM users. AOM use was associated with lower fracture incidence: weighted HR of 0.52 (95% CI 0.29, 0.94) at 1 year and weighted HR of 0.68 (95% CI 0.47, 0.99) at 3 years. CONCLUSIONS: AOM initiation within 90 days of chronic GC use was associated with a fracture reduction of 48% at 1 year and 32% at 3 years.

Effect of the women's health initiative on prescription anti-osteoporosis medication utilization.

UNLABELLED: Publication of the Women's Health Initiative (WHI) resulted in a 39% reduction in hormone therapy utilization and a 29% increase in the use of new anti-osteoporosis medications. Overall, the prevalence of prescription anti-osteoporosis medication use declined following the WHI. This has important implications for osteoporosis prevention and treatment. INTRODUCTION: Women who discontinued hormone therapy (HT) following the Women's Health Initiative (WHI) may have been more likely to initiate treatment with newer anti-osteoporosis medications (AOM). The objective of this study was to examine the influence of the WHI on AOM utilization among a nationally representative sample of older adult women in the U.S. METHODS: We used the Medical Expenditure Panel Survey (MEPS) to examine AOM utilization among women aged 50 years and older. National estimates of AOM utilization were predicted from a sample of 2089 women interviewed five times between 2002 and 2003. AOM utilization was dichotomized for HT and newer AOM. Generalized estimating equations were used to predict odds ratios (OR) for AOM utilization controlling for potential predisposing, enabling, and need confounders. RESULTS: Prior to the WHI, there were 8.7 and 3.6 million U.S. women using HT and newer AOM, respectively. One year following publication of the WHI, 5.3 million HT users persisted [OR 0.638 (95% CI: 0.617, 0.756)] while 4.7 million women used newer AOM [1.337 (95% CI: 1.120, 1.597)]. CONCLUSIONS: Although reductions in HT utilization were accompanied by increased utilization of newer AOM, treatment prevalence for osteoporosis remains sub-optimal.

A basis for a visual language for describing, archiving and analyzing functional models of complex biological systems.

BACKGROUND: We propose that a computerized, internet-based graphical description language for systems biology will be essential for describing, archiving and analyzing complex problems of biological function in health and disease. RESULTS: We outline here a conceptual basis for designing such a language and describe BioD, a prototype language that we have used to explore the utility and feasibility of this approach to functional biology. Using example models, we demonstrate that a rather limited lexicon of icons and arrows suffices to describe complex cell-biological systems as discrete models that can be posted and linked on the internet. CONCLUSIONS: Given available computer and internet technology, BioD may be implemented as an extensible, multidisciplinary language that can be used to archive functional systems knowledge and be extended to support both qualitative and quantitative functional analysis.

Expression of the F glycoprotein gene from human respiratory syncytial virus in Escherichia coli: mapping of a fusion inhibiting epitope.

A cDNA copy of the gene encoding the entire amino acid sequence of the fusion (F) protein of human respiratory syncytial virus (strain A2) was inserted into a bacterial expression vector containing the lambda PR promoter. Upon heat induction, Escherichia coli cells harboring the vector produced a 45-kDa peptide which reacted with rabbit polyclonal antiserum to the native F protein. Expression of the F gene resulted in severe inhibition of bacterial growth, which was overcome by deletion of the DNA sequences encoding the F signal peptide. The region of the F protein which reacted with a virus-neutralizing and fusion-inhibiting monoclonal antibody was probed by expressing cDNA fragments encoding different protein domains in E. coli and testing antibody reactivity by Western blot analysis. Analysis of six fragments yielded an overlapping antibody-reactive region between amino acids 253 and 298. Analysis of reactivity with a cassette of synthetic peptides confirmed that the virus-neutralizing epitope mapped between residues 289 and 298 defined by the amino acid sequence M-S-I-I-K-E-E-V-L-A.

Ultrastructural aspects of ascosporulation in Arthroderma quadrifidum (=Trichophyton terrestre).

The ultrastructural features of developing and mature ascospores were delineated after mating Arthroderma quadrifidum on pablum cereal agar. Incipient ascospores each contained a granulated nucleus bounded by a nuclear envelope while presumptive ascospore cytoplasm was bounded by a double membrane and resided in glycogen-rich epiplasm of the ascus. Mature ascospores contained nuclei and mitochondria while the ascus epiplasm still retained abundant inclusions. The ascospore wall demonstrated the presence of heterogeneous material between the plasmalemma and the outer spore membrane which appeared smooth.

Origin and ultrastructure of intra-hyphal hyphae in Trichophyton terrestre and T. rubrum.

A cell observation chamber was designed to perform continuous photomicroscopic observations of hyphal anastomosis and the origin of intra-hyphal hyphae in Trichophyton terrestre and T. rubrum. These data were correlated with ultrastructural features of intra-hyphal hyphae. Hyphal fusions occurred commonly in either species of Trichophyton when incubated alone. In T. terrestre, empty phyphal segments adjoined by live units were invaded at the septa from both directions by new hyphal ingrowth. Continuous observations revealed that the intra-hyphal hyphae subsequently anastomosed via a lateral fusion peg. Similar intra-hyphal hyphae were shown in T. rubrum. Electron microscopic studies revealed ascomycetous septa in both conventional hyphae and intra-hyphal hyphae. For the latter, the cytoplasm and wall of the inner hypha were bounded by cytoplasmic organelles and another cell wall of the outer hypha.