The dissolution and solid-state behaviours of coground ibuprofen–glucosamine HCl

The cogrinding technique is one of most effective methods for improving the dissolution of poorly water-soluble drugs and it is superior to other approaches from an economical as well as an environmental standpoint, as the technique does not require any toxic organic solvents. Present work explores the role of d-glucosamine HCl (GL) as a potential excipient to improve dissolution of a low melting point drug, ibuprofen (Ibu), using physical mixtures and coground formulations. The dissolution of the poorly soluble drug has been improved by changing the ratio of Ibu:GL and also grinding time. The results also showed that although GL can enhance the solubility of Ibu, it also reduces pH around the Ibu particles which led to poor dissolution performance when the concentration of GL is high. The effect of GL on the solubility of Ibu could be misleading if the pH of the final solution was not measured. Grinding reduced the particle size of GL significantly but in case of Ibu it was less effective. Solid state analysis (XRPD, DSC, and FT-IR) showed that ibuprofen is stable under grinding conditions, but the presence of high concentration of GL in samples subjected to high grinding times caused changes in FT-IR spectrum of Ibu which could be due to intermolecular hydrogen bond or esterification between the carboxylic acid group in the ibuprofen and hydroxyl group in the GL

X-ray Fluorescence Analysis of Feldspars and Silicate Glass: Effects of Melting Time on Fused Bead Consistency and Volatilisation

Reproducible preparation of lithium tetraborate fused beads for XRF analysis of glass and mineral samples is of paramount importance for analytical repeatability. However, as with all glass melting processes, losses due to volatilisation must be taken into account and their effects are not negligible. Here the effects of fused bead melting time have been studied for four Certified Reference Materials (CRM’s: three feldspars, one silicate glass), in terms of their effects on analytical variability and volatilisation losses arising from fused bead preparation. At melting temperatures of 1065 °C, and for feldspar samples, fused bead melting times shorter than approximately 25 min generally gave rise to a greater deviation of the XRF-analysed composition from the certified composition. This variation might be due to incomplete fusion and/or fused bead inhomogeneity but further research is needed. In contrast, the shortest fused bead melting time for the silicate glass CRM gave an XRF-analysed composition closer to the certified values than longer melting times. This may suggest a faster rate of glass-in-glass dissolution and homogenization during fused bead preparation. For all samples, longer melting times gave rise to greater volatilisation losses (including sulphates and halides) during fusion. This was demonstrated by a linear relationship between SO3 mass loss and time1/2, as predicted by a simple diffusion-based model. Iodine volatilisation displays a more complex relationship, suggestive of diffusion plus additional mechanisms. This conclusion may have implications for vitrification of iodine-bearing radioactive wastes. Our research demonstrates that the nature of the sample material impacts on the most appropriate fusion times. For feldspars no less than ~25 min and no more than ~60 min of fusion at 1065 °C, using Li2B4O7 as the fusion medium and in the context of feldspar samples and the automatic fusion equipment used here, strikes an acceptable (albeit non-ideal) balance between the competing factors of fused bead quality, analytical consistency and mitigating volatilisation losses. Conversely, for the silicate glass sample, shorter fusion times of less than ~30 min under the same conditions provided more accurate analyses whilst limiting volatile losses

Development of an IT Balanced Scorecard

There is a generally acknowledged dearth of metrics for effectively measuring organizational performance. This is particularly true of the IT function, whose contribution to a firm’s “bottom line” has been frequently called to question. This paper describes the development of a performance measurement tool called the Balanced Scorecard, which can be used to assess IT performance within the context of overall corporate strategy and financial performance. Data for the scorecard was obtained via a survey of senior IT executives in various organizations. The paper concludes with a set of guidelines for successfully implementing an IT Balanced Scorecard, as well as potential pitfalls to avoid in the process

Predictors of anemia in preschool children: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

Background: A lack of information on the etiology of anemia has hampered the design and monitoring of anemia-control efforts.Objective: We aimed to evaluate predictors of anemia in preschool children (PSC) (age range: 6-59 mo) by country and infection-burden category.Design: Cross-sectional data from 16 surveys (n = 29,293) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed separately and pooled by category of infection burden. We assessed relations between anemia (hemoglobin concentration <110 g/L) and severe anemia (hemoglobin concentration <70 g/L) and individual-level (age, anthropometric measures, micronutrient deficiencies, malaria, and inflammation) and household-level predictors; we also examined the proportion of anemia with concomitant iron deficiency (defined as an inflammation-adjusted ferritin concentration <12 μg/L). Countries were grouped into 4 categories on the basis of risk and burden of infectious disease, and a pooled multivariable logistic regression analysis was conducted for each group.Results: Iron deficiency, malaria, breastfeeding, stunting, underweight, inflammation, low socioeconomic status, and poor sanitation were each associated with anemia in >50% of surveys. Associations between breastfeeding and anemia were attenuated by controlling for child age, which was negatively associated with anemia. The most consistent predictors of severe anemia were malaria, poor sanitation, and underweight. In multivariable pooled models, child age, iron deficiency, and stunting independently predicted anemia and severe anemia. Inflammation was generally associated with anemia in the high- and very high-infection groups but not in the low- and medium-infection groups. In PSC with anemia, 50%, 30%, 55%, and 58% of children had concomitant iron deficiency in low-, medium-, high-, and very high-infection categories, respectively.Conclusions: Although causal inference is limited by cross-sectional survey data, results suggest anemia-control programs should address both iron deficiency and infections. The relative importance of factors that are associated with anemia varies by setting, and thus, country-specific data are needed to guide programs

In utero exposure to malaria is associated with metabolic traits in adolescence: The Agogo 2000 birth cohort study.

OBJECTIVES: Malaria in pregnancy (MiP) contributes to fetal undernutrition and adverse birth outcomes, and may constitute a developmental origin of metabolic diseases in the offspring. In a Ghanaian birth cohort, we examined the relationships between MiP-exposure and metabolic traits in adolescence. METHODS: MiP at delivery was assessed in 155 mother-child pairs. Among the now teenaged children (mean age, 14.8 years; 53% male), we measured fasting plasma glucose (FPG), body mass index (BMI), and systolic and diastolic blood pressure (BP). Associations of MiP with the adolescents' FPG, BMI, and BP were examined by linear regression. RESULTS: At delivery, 45% were MiP-exposed, which increased FPG in adolescence, adjusted for mother's age at delivery, parity and familial socio-economic status (infected vs. uninfected: mean ΔFPG = 0.20 mmol/L; 95% confidence interval (CI): 0.01, 0.39; p = 0.049). As a trend,this was discernible for BP, particularly for microscopic infections (mean Δsystolic BP = 5.43 mmHg; 95% CI: 0.00, 10.88; p = 0.050; mean Δdiastolic BP = 3.67 mmHg; 95% CI: -0.81, 8.14; p = 0.107). These associations were largely independent of birth weight, gestational age and teenage BMI. Adolescent BMI was not related to MiP. CONCLUSIONS: In rural Ghana, exposure to malaria during fetal development contributes to metabolic conditions in young adulthood

Ethnic differences in current smoking and former smoking in the Netherlands and the contribution of socioeconomic factors: a cross-sectional analysis of the HELIUS study.

OBJECTIVES: Data exploring how much of the ethnic differences in smoking prevalence and former smoking are explained by socioeconomic status (SES) are lacking. We therefore assessed ethnic differences in smoking prevalence and former smoking and the contribution of both educational level and occupational-related SES to the observed ethnic differences in smoking behaviour. METHODS: Data of 22 929 participants (aged 18-70 years) from the multiethnic cross-sectional Healthy Life in an Urban Setting study in the Netherlands were analysed. Poisson regression models with a robust variance were used to estimate prevalence ratios. RESULTS: Compared with the Dutch, after adjustment for age and marital status, smoking prevalence was higher in men of Turkish (prevalence ratio 1.69, 95% CI 1.54 to 1.86), African Surinamese (1.55, 95% CI 1.41 to 1.69) and South-Asian Surinamese origin (1.53, 95% CI 1.40 to 1.68), whereas among women, smoking prevalence was higher in Turkish, similar in African Surinamese but lower in all other ethnic origin groups. All ethnic minority groups, except Ghanaians, had a significantly lower smoking cessation prevalence than the Dutch. Socioeconomic gradients in smoking (higher prevalence among those lower educated and with lower level employment) were observed in all groups except Ghanaian women (a higher prevalence was observed in the higher educated). Ethnic differences in smoking prevalence and former smoking are largely, but not completely, explained by socioeconomic factors. CONCLUSIONS: Our findings imply that antismoking policies designed to target smoking within the lower socioeconomic groups of ethnic minority populations may substantially reduce ethnic inequalities in smoking particularly among men and that certain groups may benefit from targeted smoking cessation interventions

Dose-dependent T-cell Dynamics and Cytokine Cascade Following rVSV-ZEBOV Immunization.

BACKGROUND: The recent West African Ebola epidemic led to accelerated efforts to test Ebola vaccine candidates. As part of the World Health Organisation-led VSV Ebola Consortium (VEBCON), we performed a phase I clinical trial investigating rVSV-ZEBOV (a recombinant vesicular stomatitis virus-vectored Ebola vaccine), which has recently demonstrated protection from Ebola virus disease (EVD) in phase III clinical trials and is currently in advanced stages of licensing. So far, correlates of immune protection are incompletely understood and the role of cell-mediated immune responses has not been comprehensively investigated to date. METHODS: We recruited 30 healthy subjects aged 18-55 into an open-label, dose-escalation phase I trial testing three doses of rVSV-ZEBOV (3×105 plaque-forming units (PFU), 3×106 PFU, 2×107 PFU) (ClinicalTrials.gov; NCT02283099). Main study objectives were safety and immunogenicity, while exploratory objectives included lymphocyte dynamics, cell-mediated immunity and cytokine networks, which were assessed using flow cytometry, ELISpot and LUMINEX assay. FINDINGS: Immunization with rVSV-ZEBOV was well tolerated without serious vaccine-related adverse events. Ebola virus-specific neutralizing antibodies were induced in nearly all individuals. Additionally, vaccinees, particularly within the highest dose cohort, generated Ebola glycoprotein (GP)-specific T cells and initiated a cascade of signaling molecules following stimulation of peripheral blood mononuclear cells with Ebola GP peptides. INTERPRETATION: In addition to a benign safety and robust humoral immunogenicity profile, subjects immunized with 2×107 PFU elicited higher cellular immune responses and stronger interlocked cytokine networks compared to lower dose groups. To our knowledge these data represent the first detailed cell-mediated immuneprofile of a clinical trial testing rVSV-ZEBOV, which is of particular interest in light of its potential upcoming licensure as the first Ebola vaccine. VEBCON trial Hamburg, Germany (NCT02283099)

Ecological Study of HIV Infection and Hypertension in Sub-Saharan Africa: Is There a Double Burden of Disease?

An ecological correlation study of the prevalence of hypertension with human immunodeficiency virus (HIV) prevalence in sub-Saharan Africa was conducted to determine the extent to which these conditions coincide at country level. Data on prevalence of hypertension were derived from a systematic search of literature published between 1975 and 2014 with corresponding national estimates on HIV prevalence and antiretroviral therapy (ART) coverage from the Demographic and Health Surveys and the joint United Nations Programme on HIV/AIDS databases. National estimates on gross national income (GNI) and under-five mortality were obtained from the World Bank database. Linear regression analyses using robust standard errors (allowing for clustering at country level) were carried out for associations of age-standardised hypertension prevalence ratios (standardized to rural Uganda’s hypertension prevalence data) with HIV prevalence, adjusted for national indicators, year of study and sex of the study population. In total, 140 estimates of prevalence of hypertension representing 25 nations were sex-and area-matched with corresponding HIV prevalence. A two-fold increase in HIV prevalence was associated with a 9.29% increase in age, sex and study year-adjusted prevalence ratio for hypertension (95% CI 2.0 to 16.5, p = 0.01), which increased to 16.3% (95% CI 9.3 to 21.1) after adjusting for under-five mortality, GNI per capita and ART coverage. Countries with a pronounced burden of HIV may also have an increased burden of non-communicable diseases such as hypertension with potential economic and health systems implications

Evaluation of sesamum gum as an excipient in matrix tablets

In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated