Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis

BACKGROUND: Treatment with glucocorticoids is associated with bone loss starting soon after therapy is initiated and an increased risk of fracture. METHODS: We performed a randomized, double-placebo, double-blind clinical trial of 18 months' duration among patients with a rheumatic disease who were starting glucocorticoids at a daily dose that was equivalent to at least 7.5 mg of prednisone. A total of 201 patients were assigned to receive either alendronate (10 mg) and a placebo capsule of alfacalcidol daily or alfacalcidol (1 mu g) and a placebo tablet of alendronate daily. The primary outcome was the change in bone mineral density of the lumbar spine in 18 months; the secondary outcome was the incidence of morphometric vertebral deformities. RESULTS: A total of 100 patients received alendronate, and 101 received alfacalcidol; 163 patients completed the study. The bone mineral density of the lumbar spine increased by 2.1 percent in the alendronate group (95 percent confidence interval, 1.1 to 3.1 percent) and decreased by 1.9 percent in the alfacalcidol group (95 percent confidence interval, -3.1 to -0.7 percent). At 18 months, the mean difference of change in bone mineral density between the two groups was 4.0 percent (95 percent confidence interval, 2.4 to 5.5 percent). Three patients in the alendronate group had a new vertebral deformity, as compared with eight patients in the alfacalcidol group (of whom three had symptomatic vertebral fractures) (hazard ratio, 0.4; 95 percent confidence interval, 0.1 to 1.4). CONCLUSIONS: During this 18-month trial in patients with rheumatic diseases, alendronate was more effective in the prevention of glucocorticoid-induced bone loss than was alfacalcidol

Is there evidence for accelerated polyethylene wear in uncemented compared to cemented acetabular components? A systematic review of the literature

Joint arthroplasty registries show an increased rate of aseptic loosening in uncemented acetabular components as compared to cemented acetabular components. Since loosening is associated with particulate wear debris, we postulated that uncemented acetabular components demonstrate a higher polyethylene wear rate than cemented acetabular components in total hip arthroplasty. We performed a systematic review of the peer-reviewed literature, comparing the wear rate in uncemented and cemented acetabular components in total hip arthroplasty. Studies were identified using MEDLINE (PubMed), EMBASE and the Cochrane Central Register of Controlled Trials. Study quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The search resulted in 425 papers. After excluding duplicates and selection based on title and abstracts, nine studies were found eligible for further analysis: two randomised controlled trials, and seven observational studies. One randomised controlled trial found a higher polyethylene wear rate in uncemented acetabular components, while the other found no differences. Three out of seven observational studies showed a higher polyethylene wear in uncemented acetabular component fixation; the other four studies did not show any differences in wear rates. The available evidence suggests that a higher annual wear rate may be encountered in uncemented acetabular components as compared to cemented components

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

Solutions of Initial Value Problems with Non-Singular, Caputo Type and Riemann-Liouville Type, Integro-Differential Operators

Motivated by the recent interest in generalized fractional order operators and their applications, we consider some classes of integro-differential initial value problems based on derivatives of the Riemann–Liouville and Caputo form, but with non-singular kernels. We show that, in general, the solutions to these initial value problems possess discontinuities at the origin. We also show how these initial value problems can be re-formulated to provide solutions that are continuous at the origin but this imposes further constraints on the system. Consideration of the intrinsic discontinuities, or constraints, in these initial value problems is important if they are to be employed in mathematical modelling applications

Coordinated optimization of visual cortical maps (II) Numerical studies

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractable coordinated optimization models and solved representative examples in which a spatially complex organization of the orientation preference map is induced by inter-map interactions. We found that attractor solutions near symmetry breaking threshold predict a highly ordered map layout and require a substantial OD bias for OP pinwheel stabilization. Here we examine in numerical simulations whether such models exhibit biologically more realistic spatially irregular solutions at a finite distance from threshold and when transients towards attractor states are considered. We also examine whether model behavior qualitatively changes when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. Our numerical results support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the spatially irregular architecture of the visual cortex. We discuss several alternative scenarios and additional factors that may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with arXiv:1102.335

A Systematic Approach to Delay Functions

We present a systematic introduction to a class of functions that provide fundamental solutions for autonomous linear integer-order and fractional-order delay differential equations. These functions, referred to as delay functions, are defined through power series or fractional power series, with delays incorporated into their series representations. Using this approach, we have defined delay exponential functions, delay trigonometric functions and delay fractional Mittag-Leffler functions, among others. We obtained Laplace transforms of the delay functions and demonstrated how they can be employed in finding solutions to delay differential equations. Our results, which extend and unify previous work, offer a consistent framework for defining and using delay functions

Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L