Associations of plasma fibrinogen and factor VII clotting activity with coronary heart disease and stroke: prospective cohort study from the screening phase of the Thrombosis Prevention Trial.

BACKGROUND: As with 'conventional' risk factors such as cholesterol and smoking, there is a need for large, long-term prospective studies on hemostatic factors. OBJECTIVES: To investigate the prospective relationship of fibrinogen and factor VII clotting activity (FVIIc) with risk of coronary heart disease (CHD) and stroke in a study with a large number of outcomes over a period of 15 years. PATIENTS/METHODS: A cohort of 22 715 men aged 45-69 years was screened for participation in the Thrombosis Prevention Trial. Men were followed up for fatal and non-fatal CHD and stroke events. There were 1515 CHD events (933 CHD deaths) and 391 strokes (180 stroke deaths). Hazard ratios (HRs) and 95% confidence intervals are expressed per standardized increase in log fibrinogen and log FVIIc, adjusting for age, trial treatment group, conventional CHD risk factors and regression dilution bias. RESULTS: Hazard ratios for fibrinogen were 1.52 (1.37-1.70) for all CHD events, and 1.36 (1.09-1.69) for all strokes. Exclusion of events within the first 10 years showed a persistent association between CHD and fibrinogen, with an adjusted HR of 1.93 (1.42-2.64). The HRs for FVIIc, adjusting for age and trial treatment, were 1.07 (1.01-1.12) for all CHD events and 1.07 (0.97-1.20) for all strokes, and the fully adjusted HRs were, respectively, 0.97 (0.84-1.05) and 1.07 (0.85-1.33). CONCLUSIONS: The persisting association between fibrinogen and CHD beyond 10 years may imply a causal effect. There is a small effect of FVIIc on CHD, after adjustment for age and trial treatment, but no association independent of other risk factors

Improving evidence-based risk-benefit decision-making of medicines for children

Risk-benefit assessment for decision-making based on evidence is a subject of continuing interest. However, randomised clinical trials evidence of risks and benefits are not always available especially for drugs used in children mainly due to ethical concern of children being subjects of clinical trials. This thesis appraises risk-benefit evidence from published trials in children for the case study; assesses the risk-benefit balance of drugs, proposes a framework for risk-benefit evidence synthesis, and demonstrates the extent of its contribution. The review shows trial designs lack safety planning leading to inconsistency safety reporting, and lack of efficacy evidence. The General Practice Research Database (GPRD) data was exploited to synthesise evidence of risks of cisapride and domperidone in children with gastro-oesophageal reflux as a case study. Efficacy data are only available through review evidence. Analysis of prescribing trends does not identify further risk-benefit issues but suggest the lack of evidence has led to inappropriate prescribing in children. Known adverse events are defined from the British National Formulary and quantified. Proportional reporting ratio technique is applied to other clinical events to generate potential safety signals. Signals are validated; and analysed for confirmatory association through covariates adjustment in regressions. The degree of associations between signals and drugs are assessed using Bradford Hill’s criteria for causation. Verified risks are known adverse events with 95% statistical significance, and signals in abdominal pain group and bronchitis and bronchiolitis group. The drugs’ risk-benefit profiles are illustrated using the two verified signals and an efficacy outcome. Sensitivity of input parameters is studied via simulations. The findings are used to hypothetically advise risk-benefit aspects of trial designs. The value of information from this study varies between stakeholders and the keys to communicating risks and benefits lie in presentation and understanding. The generalisability and scope of the proposed methods are discussed

ENHANCEMENT OF GAMBE CLAY USING UN-FERMENTABLE POLYMERS FOR DRILLING MUD FORMULATION

There is availability and large deposits of bentonite (700 million tons in North Eastern part) in Nigeria but the clays had not been abundantly harnessed and enhanced with polymer for drilling fluid formulation because they are mostly composed of calcium montmorillonite. This work was aimed at enhancing Gambe clay using un-fermentable polymers (three carboxy methyl cellulose (CMC) with different average molecular weight). The clay was obtained from Gambe town in Adamawa State, Nigeria, beneficiated for quartz removal, as well as enhancement with Na2CO3 (6 wt.%). The mineral and oxides composition of the clay was determined using X-ray diffraction and X-ray fluorescence analyses respectively, and finally used to formulate the drilling fluid. The effect of the polymer on the rheological and physico-chemical properties of the formulated drilling fluid was investigated employing FANN 35SA viscometer.  It was found that the carboxy methyl cellulose enhanced the plastic viscosity from 1.5 cP to 34 cP and the apparent viscosity from 2.25 cP to 44 cP. The higher the average molecular weight of the sodium carboxy methyl cellulose the higher the apparent and plastic viscosities of the formulated fluid. Similarly, the resultant viscosities compared well with that of commercial standard of 15 cP and 14 cP of apparent and plastic viscosities respectively. The sets of data generated from this work is going to be very useful for water and oil/gas drilling operations. http://dx.doi.org/10.4314/njt.v36i1.1

Fabrication and Characterization of Locally Woven Polyester Fibre Reinforced Polyester Composites

Properties of composite moulded using locally woven polyester fibre werestudied. The results showed that though properties of polyester resin were improved upon, but were far lower than composites obtained using fibre such as glass. The density of the composite was low compared to glass fibre reinforced composite. The composite moulded at pressure of 388.132kN/m2has the best properties; tensile strength 85MN/m2, modulus of elasticity 1.846GN/m2, impact strength 227.5kJ/m2 and modulus of rupture 9.910GN/m2

EFFECTS OF NaOH MODIFICATION ON THE MECHANICAL PROPERTIES OF BAOBAB POD FIBER REINFORCED LDPE COMPOSITES

In order to improve properties of natural fibers as reinforcement, different treatment methods have being adopted by researchers. However, the use of sodium hydroxide (NaOH) for the treatment of baobab pod fiber as reinforcement in low density polyethylene is sparsely reported. Therefore, this study, investigated the effect of 2 wt%, 4 wt% 6 wt%, 8 wt% and 10 wt%  concentration of NaOH on baobab pod fibers as reinforcement for low density polyethylene (LDPE). Two roll mill machine and hydraulic press at a pressure of 10 kN and temperature of 120oC aided the production of the composite. FT-IR was used to analyze the functional groups of the treated and un-treated fibers. The result showed the disappearance of the peak 1550 cm-1 corresponding to lignin after modification. Further, the composites were characterized for the following tensile strength (TS), modulus of elasticity (MOE), elongation at break, impact strength and water absorption. Preliminary studies on the effect of loading of the unmodified baobab fiber in the LDPE matrix showed desirable properties at 10 wt%, where fiber content was in the range of 5 wt% to 30 wt% at interval of 5 wt%. The composite produced from the 8 wt% NaOH modified fiber had the highest tensile strength, MOE, elongation at break. At this modification level, the tensile strength, MOE and elongation at break were about 75.48%, 92.18% and 28% respectively higher than the composite produced from unmodified fiber. Composite produced with 10 wt% NaOH modified fiber exhibited least water absorption of 1.80%, which was 50% lower than unmodified. These showed that the modification of the fiber improved the composite properties. These properties compared favorably with some reported properties for natural fiber reinforced polymer composites. http://dx.doi.org/10.4314/njt.v36i1.1

Extraction and characterization of chitin and chitosan from Nigerian shrimps

Chitin was synthesized from Nigerian brown shrimps by a chemical process involving demineralization and deproteinisation. Deacetylation of the chitin was conducted to obtain Chitosan. The chitin and chitosan were characterized using FTIR, XRD and SEM. Proximate and elemental analysis were also conducted. The percentage yield of chitin was 8.9%. The degree of deacetylation of chitin was found to be 50.64% which was a low value compared to previous works and can be attributed to the low alkali concentration and heating time. XRD patterns indicated that chitin was more crystalline than the corresponding chitosan. FTIR spectra indicated the presence of functional groups associated with different bands, the intensities and stretching established that the samples are chitin and chitosan. SEM analysis also indicated morphological differences between the chitin and chitosan.Keywords: Deacetylation, biodegradable, characterization, deproteinisation, demineralizatio

Parmsurv: a SAS Macro for Flexible Parametric Survival Analysis with Long-Term Predictions

Health economic evaluations often require predictions of survival rates beyond the follow-up period. Parametric survival models can be more convenient for economic modelling than the Cox model. The generalized gamma (GG) and generalized F (GF) distributions are extensive families that contain almost all commonly used distributions with various hazard shapes and arbitrary complexity. In this study, we present a new SAS macro for implementing a wide variety of flexible parametric models including the GG and GF distributions and their special cases, as well as the Gompertz distribution. Proper custom distributions are also supported. Different from existing SAS procedures, this macro not only supports regression on the location parameter but also on ancillary parameters, which greatly increases model flexibility. In addition, the SAS macro supports weighted regression, stratified regression and robust inference. This study demonstrates with several examples how the SAS macro can be used for flexible survival modeling and extrapolation.Comment: 15 pages, 1 figure, 10 tables, accepted by The Clinical Data Science Conference - PHUSE US Connect 202

Does a monetary incentive improve the response to a postal questionnaire in a randomised controlled trial? : the MINT incentive study

Background: Sending a monetary incentive with postal questionnaires has been found to improve the proportion of responders, in research in non-healthcare settings. However, there is little research on use of incentives to improve follow-up rates in clinical trials, and existing studies are inconclusive. We conducted a randomised trial among participants in the Managing Injuries of the Neck Trial (MINT) to investigate the effects on the proportion of questionnaires returned and overall non-response of sending a £5 gift voucher with a follow-up questionnaire. Methods: Participants in MINT were randomised to receive either: (a) a £5 gift voucher (incentive group) or (b) no gift voucher (no incentive group), with their 4 month or 8 month follow-up questionnaire. We recorded, for each group, the number of questionnaires returned, the number returned without any chasing from the study office, the overall number of non-responders (after all chasing efforts by the study office), and the costs of following up each group. Results: 2144 participants were randomised, 1070 to the incentive group and 1074 to the no incentive group. The proportion of questionnaires returned (RR 1.10 (95% CI 1.05, 1.16)) and the proportion returned without chasing (RR 1.14 (95% CI 1.05, 1.24) were higher in the incentive group, and the overall non-response rate was lower (RR 0.68 (95% CI 0.53, 0.87)). Adjustment for injury severity and hospital of recruitment to MINT made no difference to these results, and there were no differences in results between the 4-month and 8-month follow up questionnaires. Analysis of costs suggested a cost of £67.29 per additional questionnaire returned. Conclusion: Monetary incentives may be an effective way to increase the proportion of postal questionnaires returned and minimise loss to follow-up in clinical trials

Structured benefit-risk assessment: a review of key publications and initiatives on frameworks and methodologies.

Introduction The conduct of structured benefit-risk assessment (BRA) of pharmaceutical products is a key area of interest for regulatory agencies and the pharmaceutical industry. However, the acceptance of a standardized approach and implementation are slow. Statisticians play major roles in these organizations, and have a great opportunity to be involved and drive the shaping of future BRA. Method We performed a literature search of recent reviews and initiatives assessing BRA methodologies, and grouped them to assist those new to BRA in learning, understanding, and choosing methodologies. We summarized the key points and discussed the impact of this emerging field on various stakeholders, particularly statisticians in the pharmaceutical industry. Results We provide introductory, essential, special interest, and further information and initiatives materials that direct readers to the most relevant materials, which were published between 2000 and 2013.  Based on recommendations in these materials we supply a toolkit of advocated BRA methodologies. Discussion Despite initiatives promoting these methodologies, there are still barriers, one of which being the lack of a consensus on the most appropriate methodologies among stakeholders. However, this opens up opportunities, for statisticians in the pharmaceutical industry especially, to champion appropriate BRA methodology use throughout the pharmaceutical product lifecycle. Conclusions This article may serve as a starting point for discussions and to reach a mutual consensus for methodology selection in a particular situation. Regulators and pharmaceutical industry should continue to collaborate to develop and take forward BRA methodologies, and by clear communication develop a mutual understanding of the key issues. Copyright © 2015 John Wiley & Sons, Ltd