Context:
Denosumab 60 mg sc injection every 6 months for 36 months was well tolerated and effective in reducing the incidence of vertebral, nonvertebral, and hip fracture in predominantly Caucasian ...postmenopausal women with osteoporosis.
Objective:
The objective of this phase 3 fracture study was to examine the antifracture efficacy and safety of denosumab 60 mg in Japanese women and men with osteoporosis compared with placebo.
Design and Setting:
A randomized, double-blind, placebo-controlled trial with an open-label active comparator as a referential arm was conducted.
Patients:
Subjects were 1262 Japanese patients with osteoporosis aged 50 years or older, who had one to four prevalent vertebral fractures.
Intervention:
Subjects were randomly assigned to receive denosumab 60 mg sc every 6 months (n = 500), placebo for denosumab (n = 511), or oral alendronate 35 mg weekly (n = 251). All subjects received daily supplements of calcium and vitamin D.
Main Outcome Measure:
The primary endpoint was the 24-month incidence of new or worsening vertebral fracture for denosumab vs placebo.
Results:
Denosumab significantly reduced the risk of new or worsening vertebral fracture by 65.7%, with incidences of 3.6% in denosumab and 10.3% in placebo at 24 months (hazard ratio 0.343; 95% confidence interval 0.194–0.606, P = .0001). No apparent difference in adverse events was found between denosumab and placebo during the first 24 months of the study.
Conclusion:
These results provide evidence of the efficacy and safety of denosumab 60 mg sc every 6 months in Japanese subjects with osteoporosis.
Introduction
In anti-osteoporosis drug trials, vitamin D and calcium (Ca) are common supplements; however, the optimal dose of each is unclear. Using data from the randomized, double-blind, ...placebo-controlled DIRECT trial, we assessed whether baseline serum 25-hydroxy vitamin D (25OHD) level influences the efficacy of denosumab co-administered with vitamin D and Ca.
Materials and methods
In this prespecified sub-analysis, subjects with primary osteoporosis who received denosumab or placebo, plus vitamin D (≥ 400 IU/day) and Ca (≥ 600 mg/day), were classified as 25(OH)D deficient (< 20 ng/mL), insufficient (≥ 20 to < 30 ng/mL), and sufficient (≥ 30 ng/mL). Study endpoints included absolute serum 25(OH)D level at baseline, 12 months, and 24 months; change in serum 25(OH)D and bone mineral density (BMD) status from baseline; and incidence of new vertebral fractures at 24 months.
Results
In 475 denosumab-treated and 481 placebo-treated subjects, proportions with deficient/insufficient/sufficient 25(OH)D at baseline were 53.1%/37.1%/9.9% and 50.9%/42.0%/7.1%, respectively. Supplementation significantly increased mean serum 25(OH)D levels; at 24 months, mean levels were > 30 ng/mL (sufficient) in both treatment groups. Increase in BMD over time was higher in the denosumab group vs. placebo group in all three vitamin D status groups. At month 24, denosumab-treated subjects with deficient/insufficient baseline 25(OH)D had a significantly lower risk of new vertebral fracture vs. placebo-treated subjects.
Conclusion
Among DIRECT trial subjects supplemented with ≥ 400 IU/day of vitamin D and ≥ 600 mg/day of Ca, baseline 25(OH)D sufficiency may not influence the efficacy of denosumab in increasing BMD or preventing vertebral fractures.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this post hoc analysis of the Denosumab Fracture Intervention Randomized Placebo-Controlled Trial (DIRECT) in Japanese postmenopausal women and men with osteoporosis, we evaluated the relationship ...between vertebral fracture risk and both bone mineral density (BMD) T-score and percent change after 24 months of denosumab treatment at total hip, femoral neck, and lumbar spine. Logistic regression analysis was performed and the proportion of treatment effect explained by BMD in vertebral fracture risk was estimated. The results demonstrate that both total hip BMD T-score and change can be strong predictors of subsequent fracture risk, and that total hip BMD change explained 73%, while T-score explained 23%, of the treatment effect. In contrast, neither femoral neck BMD change nor T-score can predict the effect of denosumab on vertebral fracture risk. Furthermore, although lumbar spine BMD T-score was associated with vertebral fracture incidence, lumbar spine BMD change was inversely related to vertebral fracture risk. Because there was no relationship between lumbar spine BMD change and T-score at 24 months of denosumab treatment, and because there can be small undetectable vertebral deformities that may increase BMD values, these results suggest that lumbar spine BMD change is not a good surrogate for vertebral fracture risk assessment. It is suggested that both total hip BMD change and T-score can be good surrogates for predicting vertebral fracture risk in Japanese patients with osteoporosis under denosumab treatment.
ClinicalTrials.gov identifier: NCT00680953.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This study presents a comparative performance analysis involving single- and double-stage photovoltaic (PV) systems, which are connected to a three-phase four-wire electrical system by means of a ...four-leg inverter topology. The double-stage PV system is composed of a step-up DC/DC converter and a four-leg grid-connected inverter, while in the single-stage PV system the PV array is directly connected to the inverter DC bus. In addition to the active power injection into the grid, both PV systems have two attractive features, described as follows: (i) power quality improvement due to their capability to perform active power-line conditioning, such as load harmonic current suppression, reactive power compensation, and load unbalance compensation; (ii) dynamic improvement in the occurrence of abrupt solar irradiation variations, which is achieved through the implementation of a feed-forward control loop (FFCL) acting directly in the inverter DC-bus voltage control loop, resulting in speeding up of the dynamics of both the DC-bus voltage and the injected grid-inverter currents. The referred comparative analysis addresses the static and dynamic performances considering the PV systems operating under the action of the FFCL, as well as performing active power-line conditioning. Simulation and experimental results are presented to evaluate and validate the proposed study.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
It is well-known that performance of photovoltaic (PV) systems can be severely deteriorated when PV arrays are subjected to partial shading conditions, once the traditional techniques used for ...maximum power point tracking (MPPT) could not operate in the global maximum power point (GMPP). Thus, to overcome this problem and achieve the GMPP, four MPPT techniques bio-inspired in the grey wolf optimisation (GWO) are presented. These MPPT techniques, which are named as GWO, GWO-Beta, GWO-IC (Incremental Conductance), and GWO-P&O (Perturb and Observe), are evaluated and compared to each other by employing a double-stage three-phase grid-connected PV system, which is composed of DC/DC converter and three-phase inverter. Commonly, the DC-bus voltage regulation of double-stage PV systems presents slow dynamic behaviour to avoid disturbances in the currents injected into the grid. As a result, MPPT algorithms suffer with this problem since they must be executed considering this condition. To overcome this problem, a feed-forward control loop (FFCL) is implemented to improve the DC-bus voltage regulation during abrupt solar irradiance changes, as well as accelerating the MPPT algorithms dynamics. By means of extensive experimental and simulation results, the performance and effectiveness of the four MPPT techniques, as well as the FFCL, are evaluated.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Clinical Trials Express Nakamura, Toshitaka; Matsumoto, Toshio; Sugimoto, Toshitsugu ...
The journal of clinical endocrinology and metabolism,
2014-July, Volume:
99, Issue:
7
Journal Article
Peer reviewed
CONTEXT:Denosumab 60 mg sc injection every 6 months for 36 months was well tolerated and effective in reducing the incidence of vertebral, nonvertebral, and hip fracture in predominantly Caucasian ...postmenopausal women with osteoporosis.
OBJECTIVE:The objective of this phase 3 fracture study was to examine the antifracture efficacy and safety of denosumab 60 mg in Japanese women and men with osteoporosis compared with placebo.
DESIGN AND SETTING:A randomized, double-blind, placebo-controlled trial with an open-label active comparator as a referential arm was conducted.
PATIENTS:Subjects were 1262 Japanese patients with osteoporosis aged 50 years or older, who had one to four prevalent vertebral fractures.
INTERVENTION:Subjects were randomly assigned to receive denosumab 60 mg sc every 6 months (n = 500), placebo for denosumab (n = 511), or oral alendronate 35 mg weekly (n = 251). All subjects received daily supplements of calcium and vitamin D.
MAIN OUTCOME MEASURE:The primary endpoint was the 24-month incidence of new or worsening vertebral fracture for denosumab vs placebo.
RESULTS:Denosumab significantly reduced the risk of new or worsening vertebral fracture by 65.7%, with incidences of 3.6% in denosumab and 10.3% in placebo at 24 months (hazard ratio 0.343; 95% confidence interval 0.194–0.606, P = .0001). No apparent difference in adverse events was found between denosumab and placebo during the first 24 months of the study.
CONCLUSION:These results provide evidence of the efficacy and safety of denosumab 60 mg sc every 6 months in Japanese subjects with osteoporosis.
Forty-one open reading frames (ORFs) were identified in a 32-kb DNA fragment of alkaliphilic Bacillus sp. C-125. A similarity search using the BSORF database found 37 ORFs with significant sequence ...similarity to B. subtilis RNA polymerase subunits, elongation factor G. elongation factor Tu, and ribosomal proteins. Each ORF product showed more than 70% identity to those of B. subtilis. Gene organization in the region of str, S10, spc, and the alpha cluster was highly conserved among three stra
AIM:To examine whether commensal bacteria are a contributing cause of stress-related mucosal inflammation.METHODS:Human peripheral blood monocyte-deriveddendritic cells(MoDCs)were stimulated by ...commensal bacterial strains,including Escherichia coli,Clostridium clostridioforme,Bacteroides vulgatus(B.vulgatus),Fusobacterium varium(F.varium),and Lactobacillus delbrueckii subsp.bulgaricus.After incubation,corticotropin-releasing factor(CRF)and urocortin 1(UCN1)mRNA in the cells was examined by real-time reverse transcription polymerase chain reaction.Supernatants from the cells were tested for CRF and UCN1 using an enzyme-linked immunosorbent assay.RESULTS:Both CRF and UCN1 were significantly augmented by B.vulgatus and F.varium at both the mRNA and protein levels.In particular,B.vulgatus stimulated human MoDCs,resulting in extremely high levels of CRF and UCN1.CONCLUSION:Stimulation of MoDCs by B.vulgatus and F.varium may be associated with CRF/UCN1-related intestinal disorders,such as irritable bowel syndrome and inflammatory bowel disease.
The aim of the present study is to contribute to the operation and control of wind turbines situated in mountainous areas, which often suffer from over-speed due to highly gusty mountainous winds ...with high shear. By adding an electric load-brake to conventional pitch control we can suppress over-speed and increase power production.
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BFBNIB, NUK, OILJ, PNG, SAZU, UKNU, UL, UM, UPUK
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