Randomized controlled trial of Vitamin D supplementation in older people to optimize bone health

Background: Vitamin D insufficiency is common in older people and may lead to increased bone resorption, bone loss, and increased falls and fractures. However, clinical trials assessing the effect of vitamin D supplementation on bone mineral density (BMD) have yielded conflicting results. Objectives This study examined the effect of vitamin D supplementation on BMD at the hip, using dual-energy X-ray absorptiometry. Methods: A total of 379 adults aged ≥70 y (48% women; mean age: 75 y) from the northeast of England were randomly allocated to 1 of 3 doses of vitamin D 3 [12,000 international units (IU), 24,000 IU, or 48,000 IU] given once a month. The primary outcome was change in BMD (δBMD) at the hip. Secondary endpoints comprised the dose effects on femoral neck BMD, falls, circulating calciotropic hormones, bone turnover markers, and adverse events. Results: The mean ± SD baseline plasma 25-hydroxyvitamin D [25(OH)D] concentration was 40.0 ± 20.1 nmol/L, which increased after 12 mo to a mean 25(OH)D of 55.9, 64.6, or 79.0 nmol/L for participants receiving a monthly dose of 12,000, 24,000, or 48,000 IU, respectively (P < 0.01 for difference). There was no between-group difference in δBMD. However, parathyroid hormone concentrations decreased in all 3 groups, with a significantly greater decrease in the 48,000-IU group compared with the 12,000-IU group (P < 0.01). There were no differences in any adverse events between groups, with 3 cases of hypercalcemia, none of nephrolithiasis, and 249 falls observed. Conclusions: There was no difference in change in BMD over 12 mo between the 3 doses of vitamin D, suggesting no effect of the intervention or a similar attenuation of the anticipated decrease in BMD over 12 mo. The treatment was safe and effective in increasing plasma 25(OH)D concentrations, with no dose-related adverse events. This trial was registered at the EU Clinical Trials Register (EudraCT 2011-004890-10) and the ISRCTN Registry (ISRCTN35648481)

Randomized controlled trial of Vitamin D supplementation in older people to optimize bone health

Background: Vitamin D insufficiency is common in older people and may lead to increased bone resorption, bone loss, and increased falls and fractures. However, clinical trials assessing the effect of vitamin D supplementation on bone mineral density (BMD) have yielded conflicting results. Objectives This study examined the effect of vitamin D supplementation on BMD at the hip, using dual-energy X-ray absorptiometry. Methods: A total of 379 adults aged ≥70 y (48% women; mean age: 75 y) from the northeast of England were randomly allocated to 1 of 3 doses of vitamin D 3 [12,000 international units (IU), 24,000 IU, or 48,000 IU] given once a month. The primary outcome was change in BMD (δBMD) at the hip. Secondary endpoints comprised the dose effects on femoral neck BMD, falls, circulating calciotropic hormones, bone turnover markers, and adverse events. Results: The mean ± SD baseline plasma 25-hydroxyvitamin D [25(OH)D] concentration was 40.0 ± 20.1 nmol/L, which increased after 12 mo to a mean 25(OH)D of 55.9, 64.6, or 79.0 nmol/L for participants receiving a monthly dose of 12,000, 24,000, or 48,000 IU, respectively (P < 0.01 for difference). There was no between-group difference in δBMD. However, parathyroid hormone concentrations decreased in all 3 groups, with a significantly greater decrease in the 48,000-IU group compared with the 12,000-IU group (P < 0.01). There were no differences in any adverse events between groups, with 3 cases of hypercalcemia, none of nephrolithiasis, and 249 falls observed. Conclusions: There was no difference in change in BMD over 12 mo between the 3 doses of vitamin D, suggesting no effect of the intervention or a similar attenuation of the anticipated decrease in BMD over 12 mo. The treatment was safe and effective in increasing plasma 25(OH)D concentrations, with no dose-related adverse events. This trial was registered at the EU Clinical Trials Register (EudraCT 2011-004890-10) and the ISRCTN Registry (ISRCTN35648481)

Sequences of Regressions Distinguish Nonmechanical from Mechanical Associations between Metabolic Factors, Body Composition, and Bone in Healthy Postmenopausal Women

Background: There is increasing recognition of complex interrelations between the endocrine functions of bone and fat tissues or organs.  Objective: The objective was to describe nonmechanical and mechanical links between metabolic factors, body composition, and bone with the use of graphical Markov models.  Methods: Seventy postmenopausal women with a mean ± SD age of 62.3 ± 3.7 y and body mass index (in kg/m2) of 24.9 ± 3.8 were recruited. Bone outcomes were peripheral quantitative computed tomography measures of the distal and diaphyseal tibia, cross-sectional area (CSA), volumetric bone mineral density (vBMD), and cortical CSA. Biomarkers of osteoblast and adipocyte function were plasma concentrations of leptin, adiponectin, osteocalcin, undercarboxylated osteocalcin (UCOC), and phylloquinone. Body composition measurements were lean and percent fat mass, which were derived with the use of a 4-compartment model. Sequences of Regressions, a subclass of graphical Markov models, were used to describe the direct (nonmechanical) and indirect (mechanical) interrelations between metabolic factors and bone by simultaneously modeling multiple bone outcomes and their relation with biomarker outcomes with lean mass, percent fat mass, and height as intermediate explanatory variables.  Results: The graphical Markov models showed both direct and indirect associations linking plasma leptin and adiponectin concentrations with CSA and vBMD. At the distal tibia, lean mass, height, and adiponectin-UCOC interaction were directly explanatory of CSA (R2 = 0.45); at the diaphysis, lean mass, percent fat mass, leptin, osteocalcin, and age-adiponectin interaction were directly explanatory of CSA (R2 = 0.49). The regression models exploring direct associations for vBMD were much weaker, with R2 = 0.15 and 0.18 at the distal and diaphyseal sites, respectively. Lean mass and UCOC were associated, and the global Markov property of the graph indicated that this association was explained by osteocalcin.  Conclusions: This study, to our knowledge, offers a novel approach to the description of the complex physiological interrelations between adiponectin, leptin, and osteocalcin and the musculoskeletal system. There may be benefits to jointly targeting both systems to improve bone health

Measurement of the t-channel single-top-quark production cross section and of the |Vtb| CKM matrix element in pp collisions at SQR = 8 TeV

Measurements are presented of the t -channel single-top-quark production cross section in proton-proton collisions at s&#8730; = 8 TeV. The results are based on a data sample corresponding to an integrated luminosity of 19.7 fb &#8722;1 recorded with the CMS detector at the LHC. The cross section is measured inclusively, as well as separately for top (t) and antitop (t¯) , in final states with a muon or an electron. The measured inclusive t -channel cross section is &#963; t -ch. = 83 . 6 ± 2 . 3 (stat.) ± 7 . 4 (syst.) pb. The single t and t¯ cross sections are measured to be &#963; t -ch. ( t ) = 53 . 8 ± 1 . 5 (stat.) ± 4 . 4 (syst.) pb and &#963; t -ch. (t¯) = 27 . 6 ± 1 . 3 (stat.) ± 3 . 7 (syst.) pb, respectively. The measured ratio of cross sections is R t -ch. = &#963; t -ch. (t) /&#963; t -ch. (t¯) = 1 . 95 ± 0 . 10 (stat.) ± 0 . 19 (syst.), in agreement with the standard model prediction. The modulus of the Cabibbo-Kobayashi-Maskawa matrix element V tb is extracted and, in combination with a previous CMS result at s&#8730; = 7 TeV, a value | V tb | = 0 . 998 ± 0 . 038 (exp.) ± 0 . 016 (theo.) is obtained

Essential medicines in Tanzania : does the new delivery system improve supply and accountability?

Objective: Assess whether reform in the Tanzanian medicines delivery system from a central 'push' kit system to a decentralized 'pull' Integrated Logistics System (ILS) has improved medicines accountability. Methods: Rufiji District in Tanzania was used as a case study. Data on medicines ordered and patients seen were compiled from routine information at six public health facilities in 1999 under the kit system and in 2009 under the ILS. Three medicines were included for comparison: an antimalarial, anthelmintic and oral rehydration salts (ORS). Results: The quality of the 2009 data was hampered by incorrect quantification calculations for orders, especially for antimalarials. Between the periods 1999 and 2009, the percent of unaccounted antimalarials fell from 60 to 18%, while the percent of unaccounted anthelmintic medicines went from 82 to 71%. Accounting for ORS, on the other hand, did not improve as the unaccounted amounts increased from 64 to 81% during the same period. Conclusions: The ILS has not adequately addressed accountability concerns seen under the kit system due to a combination of governance and system-design challenges. These quantification weaknesses are likely to have contributed to the frequent periods of antimalarial stock-out experienced in Tanzania since 2009. We propose regular reconciliation between the health information system and the medicines delivery system, thereby improving visibility and guiding interventions to increase the availability of essential medicines

Equal Protection or Equal Denial: Is It Time for Racial Minorities, the Poor, Women, and Other Opressed People to Regroup?

The suspect classification approach as it pertains to women, racial minorities, and the poor will be analyzed first in order to determine what gains, if any, have been achieved and lost via this route. Then the utility of an equal protection-fundamental rights approach which may accent more concerns common to women, minorities, the poor, and other oppressed peoples will be examined. Finally, the value of a sliding-scale route to equal protection issues as a route which might permit the oppressed to present a more reasoned equal protection package to the Court, and simultaneously make it more uncomfortable for the Supreme Court to disregard the societal injustices heaped upon the poor, racial minorities, and other oppressed peoples, will be considered