Comparison of estimates and calculations of risk of coronary heart disease by doctors and nurses using different calculation tools in general practice: cross sectional study

OBJECTIVE: To assess the effect of using different risk calculation tools on how general practitioners and practice nurses evaluate the risk of coronary heart disease with clinical data routinely available in patients' records. DESIGN: Subjective estimates of the risk of coronary heart disease and results of four different methods of calculation of risk were compared with each other and a reference standard that had been calculated with the Framingham equation; calculations were based on a sample of patients' records, randomly selected from groups at risk of coronary heart disease. SETTING: General practices in central England. PARTICIPANTS: 18 general practitioners and 18 practice nurses. MAIN OUTCOME MEASURES: Agreement of results of risk estimation and risk calculation with reference calculation; agreement of general practitioners with practice nurses; sensitivity and specificity of the different methods of risk calculation to detect patients at high or low risk of coronary heart disease. RESULTS: Only a minority of patients' records contained all of the risk factors required for the formal calculation of the risk of coronary heart disease (concentrations of high density lipoprotein (HDL) cholesterol were present in only 21%). Agreement of risk calculations with the reference standard was moderate (kappa=0.33-0.65 for practice nurses and 0.33 to 0.65 for general practitioners, depending on calculation tool), showing a trend for underestimation of risk. Moderate agreement was seen between the risks calculated by general practitioners and practice nurses for the same patients (kappa=0.47 to 0.58). The British charts gave the most sensitive results for risk of coronary heart disease (practice nurses 79%, general practitioners 80%), and it also gave the most specific results for practice nurses (100%), whereas the Sheffield table was the most specific method for general practitioners (89%). CONCLUSIONS: Routine calculation of the risk of coronary heart disease in primary care is hampered by poor availability of data on risk factors. General practitioners and practice nurses are able to evaluate the risk of coronary heart disease with only moderate accuracy. Data about risk factors need to be collected systematically, to allow the use of the most appropriate calculation tools.

Dissolution rate enhancement, in vitro evaluation and investigation of drug release kinetics of chloramphenicol and sulphamethoxazole solid dispersions

Formulation of solid dispersions is one of the effective methods to increase the rate of solubilization and dissolution of poorly soluble drugs. Solid dispersions of chloramphenicol (CP) and sulphamethoxazole (SX) as model drugs were prepared by melt fusion method using polyethylene glycol 8000 (PEG 8000) as an inert carrier. The dissolution rate of CP and SX were rapid from solid dispersions with low drug and high polymer content. Characterization was performed using fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). FTIR analysis for the solid dispersions of CP and SX showed that there was no interaction between PEG 8000 and the drugs. Hyper-DSC studies revealed that CP and SX were converted into an amorphous form when formulated as solid dispersion in PEG 8000. Mathematical analysis of the release kinetics demonstrated that drug release from the various formulations followed different mechanisms. Permeability studies demonstrated that both CP and SX when formulated as solid dispersions showed enhanced permeability across Caco-2 cells and CP can be classified as well-absorbed compound when formulated as solid dispersions. © 2013 Informa Healthcare USA, Inc.

Development and formulation of wax-based transdermal drug delivery systems

Topical and transdermal formulations are promising platforms for the delivery of drugs. A unit dose topical or transdermal drug delivery system that optimises the solubility of drugs within the vehicle provides a novel dosage form for efficacious delivery that also offers a simple manufacture technique is desirable. This study used Witepsol® H15 wax as a abase for the delivery system. One aspect of this project involved determination of the solubility of ibuprofen, flurbiprofen and naproxen in the was using microscopy, Higuchi release kinetics, HyperDSC and mathematical modelling techniques. Correlations between the results obtained via these techniques were noted with additional merits such as provision of valuable information on drug release kinetics and possible interactions between the drug and excipients. A second aspect of this project involved the incorporation of additional excipients: Tween 20 (T), Carbopol®971 (C) and menthol (M) to the wax formulation. On in vitro permeation through porcine skin, the preferred formulations were: ibuprofen (5% w/w) within Witepsol®H15 + 1% w/w T; flurbiprofen (10% w/w) within Witepsol®H15 + 1% w/w T; naproxen (5% w/w) within Witepsol®H15 + 1% w/w T + 1% C and sodium diclofenac (10% w/w) within Witepsol®H15 + 1% w/w T + 1% w/w T + 1% w/w C + 5% w/w M. Unit dose transdermal tablets containing ibuprofen and diclofenac were produced with improved flux compared to marketed products; Voltarol Emugel® demonstrated flux of 1.68x10-3 cm/h compared to 123 x 10-3 cm/h for the optimised product as detailed above; Ibugel Forte® demonstrated a permeation coefficient value of 7.65 x 10-3 cm/h compared to 8.69 x 10-3 cm/h for the optimised product as described above.

The role of interoganisational tension and conflict in market creation practice

Markets exist within a world of constant exchanges which form the basis for changes and the creation of new markets. Therefore, it is important to research these exchanges. One of the areas in which market creation can be observed is interorganisational collaborations, as firms increasingly collaborate to create markets. In market creation practice, however, interorganisational tension and conflict can form from divergent approaches and vested interests of the partners. Interorganisational tension represents the opposing intentions of interorganisational forces, and conflict is generated through disagreements. The aim of this research is to investigate interorganisational tension and conflict on market creation practice. Specifically, it attempts to: (i) expand interorganisational tension and conflict and provide insights to these concepts, as well as establishing a two-dimensional interorganisational tension (productive and unproductive) understanding, (ii) explore the interactions between interorganisational tension and conflict, (iii) develop a conceptual framework that explains the level of market creation depending on the effects of interorganisational tension and conflict, (iv) develop a typology of partnering firms based on interorganisational tension and conflict practice. To achieve this aim, and to respond to the research calls, this study follows a grounded theory approach which intends to expand the understanding of interorganisational tension and conflict. According to the findings, a major characteristic of interorganisational tension is its two dimensions: productive and unproductive. However, it is the intertwined nature of tension and conflict that influences market creation. Fundamental to these are the six interorganisational tension and three conflict types revealed by the findings of this study. The core theoretical contributions of the study are a dynamic framework that portrays the dynamic interactions between interorganisational tension and conflict on market creation practice, and a typology of market-creating partnering firms. Collectively, they explicate the development of market creation practice, and firms’ reactions to interorganisational tension and conflict.

Advancing age and bleeding risk are the strongest barriers to anticoagulant prescription in atrial fibrillation

In clinical practice many patients with atrial fibrillation (AF) at high thromboembolic risk fail to receive adequate oral anticoagulation (OAC) [1]. The complex management of anticoagulant therapy [frequent international normalised ratio (INR) monitoring because of narrow therapeutic window, interaction with food and alcohol, concomitant medications and comorbities], the overestimation of bleeding risk and the underestimation of stroke risk, may partially explain physicians' reluctance to prescribe anticoagulation. In the current issue of Age and Ageing, Pugh and Mead [2] report a systematic review on physicians' attitudes concerning anticoagulant treatment among AF patients. Through surveys (questionnaire, clinical vignette and interview) on hypothetical case scenarios, they have identified the barriers to effective anticoagulant prescription, as follows: increasing age, bleeding risk or previous bleeding, fall risk, co-morbidities (e.g. chronic alcoholism or cognitive impairment) and lack of compliance. In particular, advanced age has been reported as the most striking reason for with-holding anticoagulation, while risk of falls and previous bleeding are also disproportionate barriers to warfarin prescription.

Strategy as practice:recursiveness, adaptation, and practices-in-use

In this article, a social theory framework is developed to explain the common themes of recursive and adaptive practice underpinning the existing strategic management literature. In practice, there is a coexistent tension between recursive and adaptive forms of strategic action that spans multiple levels from macro-institutional and competitive contexts to within-firm levels of analysis to individual cognition. This tension may be better understood by examining how management practices are used to put strategy into practice. Such practices span multiple levels of context and are adaptable to their circumstances of use, serving to highlight both general characteristics and localized idiosyncrasies of strategy as practice. The article develops the concept of management practices-in-use into a research agenda and nine broad research questions that may be used to investigate empirically strategy as practice.

Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The cytotoxic effects of 6-mercaptopurine (6-MP) were found to be due to drug-derived intracellular metabolites (mainly 6-thioguanine nucleotides and to some extent 6-methylmercaptopurine nucleotides) rather than the drug itself. • Current empirical dosing methods for oral 6-MP result in highly variable drug and metabolite concentrations and hence variability in treatment outcome. WHAT THIS STUDY ADDS • The first population pharmacokinetic model has been developed for 6-MP active metabolites in paediatric patients with acute lymphoblastic leukaemia and the potential demographic and genetically controlled factors that could lead to interpatient pharmacokinetic variability among this population have been assessed. • The model shows a large reduction in interindividual variability of pharmacokinetic parameters when body surface area and thiopurine methyltransferase polymorphism are incorporated into the model as covariates. • The developed model offers a more rational dosing approach for 6-MP than the traditional empirical method (based on body surface area) through combining it with pharmacogenetically guided dosing based on thiopurine methyltransferase genotype. AIMS - To investigate the population pharmacokinetics of 6-mercaptopurine (6-MP) active metabolites in paediatric patients with acute lymphoblastic leukaemia (ALL) and examine the effects of various genetic polymorphisms on the disposition of these metabolites. METHODS - Data were collected prospectively from 19 paediatric patients with ALL (n = 75 samples, 150 concentrations) who received 6-MP maintenance chemotherapy (titrated to a target dose of 75 mg m−2 day−1). All patients were genotyped for polymorphisms in three enzymes involved in 6-MP metabolism. Population pharmacokinetic analysis was performed with the nonlinear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance for the active metabolites. RESULTS - The developed model revealed considerable interindividual variability (IIV) in the clearance of 6-MP active metabolites [6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-mMPNs)]. Body surface area explained a significant part of 6-TGNs clearance IIV when incorporated in the model (IIV reduced from 69.9 to 29.3%). The most influential covariate examined, however, was thiopurine methyltransferase (TPMT) genotype, which resulted in the greatest reduction in the model's objective function (P < 0.005) when incorporated as a covariate affecting the fractional metabolic transformation of 6-MP into 6-TGNs. The other genetic covariates tested were not statistically significant and therefore were not included in the final model. CONCLUSIONS - The developed pharmacokinetic model (if successful at external validation) would offer a more rational dosing approach for 6-MP than the traditional empirical method since it combines the current practice of using body surface area in 6-MP dosing with a pharmacogenetically guided dosing based on TPMT genotype.

Paediatric drug development:reformulation, in vitro, genomic and in vivo evaluation

Angiotensin converting enzyme (ACE) inhibitors lisinopril and ramipril were selected from EMA/480197/2010 and the potassium-sparing diuretic spironolactone was selected from the NHS specials list for November 2011 drug tariff with the view to produce oral liquid formulations providing dosage forms targeting paediatrics. Lisinopril, ramipril and spironolactone were chosen for their interaction with transporter proteins in the small intestine. Formulation limitations such as poor solubility or pH sensitivity needed consideration. Lisinopril was formulated without extensive development as drug and excipients were water soluble. Ramipril and spironolactone are both insoluble in water and strategies combating this were employed. Ramipril was successfully solubilised using low concentrations of acetic acid in a co-solvent system and also via complexation with hydroxypropyl-β-cyclodextrin. A ramipril suspension was produced to take formulation development in a third direction. Spironolactone dosages were too high for solubilisation techniques to be effective so suspensions were developed. A buffer controlled pH for the sensitive drug whilst a precisely balanced surfactant and suspending agent mix provided excellent physical stability. Characterisation, stability profiling and permeability assessment were performed following formulation development. The formulation process highlighted current shortcomings in techniques for taste assessment of pharmaceutical preparations resulting in early stage research into a novel in vitro cell based assay. The formulations developed in the initial phase of the research were used as model formulations investigating microarray application in an in vitro-in vivo correlation for carrier mediated drug absorption. Caco-2 cells were assessed following transport studies for changes in genetic expression of the ATP-binding cassette and solute carrier transporter superfamilies. Findings of which were compared to in vitro and in vivo permeability findings. It was not possible to ascertain a correlation between in vivo drug absorption and the expression of individual genes or even gene families, however there was a correlation (R2 = 0.9934) between the total number of genes with significantly changed expression levels and the predicted human absorption.

Structural design of contact lens-based drug delivery systems; in vitro and in vivo studies of ocular triggering mechanisms

This study identifies and investigates the potential use of in-eye trigger mechanisms to supplement the widely available information on release of ophthalmic drugs from contact lenses under passive release conditions. Ophthalmic dyes and surrogates have been successfully employed to investigate how these factors can be drawn together to make a successful system. The storage of a drug-containing lens in a pH lower than that of the ocular environment can be used to establish an equilibrium that favours retention of the drug in the lens prior to ocular insertion. Although release under passive conditions does not result in complete dye elution, the use of mechanical agitation techniques which mimic the eyelid blink action in conjunction with ocular tear chemistry promotes further release. In this way differentiation between passive and triggered in vitro release characteristics can be established. Investigation of the role of individual tear proteins revealed significant differences in their ability to alter the equilibrium between matrix-held and eluate-held dye or drug. These individual experiments were then investigated in vivo using ophthalmic dyes. Complete elution was found to be achievable in-eye; this demonstrated the importance of that fraction of the drug retained under passive conditions and the triggering effect of in-eye conditions on the release process. Understanding both the structure-property relationship between drug and material and in-eye trigger mechanisms, using ophthalmic dyes as a surrogate, provides the basis of knowledge necessary to design ocular drug delivery vehicles for in-eye release in a controllable manner.

Üzleti kapcsolatok – vállalati szemléletmód és gyakorlat = Business relationships - approach and practice in Hungary

A tanulmányunk fókuszában a vállalatközi kapcsolatok állnak. Az üzleti kapcsolatok, s ezek eredményes és hatékony menedzselése fontos értékteremtő tényező lehet. Az üzleti vállalkozások sikerét saját teljesítményük mellett üzleti partnereik (beszállítóik, alvállalkozóik, közvetítőik, megrendelőik, vevőik) teljesítménye, s a velük való kapcsolat eredményessége és hatékonysága egyaránt befolyásolja. Kutatásunkban a Versenyképesség-kutatás 2009. évi felmérésének eredményei alapján vizsgáltuk a vállalatközi kapcsolatok jellemzőit, lehetőség szerint összevetve a tapasztalatokat a korábbi hasonló felmérések (leginkább a 2004. évi, esetenként az 1996. és 1999. évi) következtetéseivel, eredményeivel. A tanulmányban a hosszú távú vállalati kapcsolatok általános jellemzését követően a kapcsolatok értékelésében megnyilvánuló vállalati szemléletmódot elemezzük, kiemelve, hogy a vállalatvezetők véleménye szerint a stabilitás, a kiszámíthatóság szempontjai általában elsődlegesek a kapcsolatokban rejlő együttműködési, fejlesztési lehetőségekhez képest. Különböző jellemzők (pl. vállalatméret, tulajdonos, teljesítmény) alapján kialakított csoportok véleményét összevetve rámutatunk, hogy az üzleti kapcsolatok megítélésében, a partnerek felé megjelenő elvárásokban a vállalatvezetők szemléletmódjában milyen eltérések észlelhetők. A tanulmány utolsó fejezetében a vevő-szállító kapcsolatokat támogató teljesítménymérési és -menedzsment eszköztárat értékeltük: a kedvező tendenciák, javuló támogatás ellenére sem állítható, hogy megfelelő, hatékony támogatást nyújtanak a vállalati információs és kontrolling rendszerek e kapcsolatok menedzseléséhez. A kutatás eredményeinek elemzése alapján látható, hogy az üzleti kapcsolatokra irányuló növekvő figyelem még kiaknázatlan lehetőségekkel párosul: a szemléletmód és a gyakorlat további fejlődése szükséges, hogy az üzleti kapcsolatok értékteremtő tényezőként a versenyképesség megalapozását, fejlesztését szolgálhassák a vállalatok szélesebb köre számára. ___________ The paper analyses the business relationships characteristics of Hungarian companies, based on data of the Competitiveness research program. Our goal was to characterize the business relationships and the causes of long term contracts and to analyse the view of different executives concerning the value of customer and supplier relationships. The last chapter of the paper evaluate the supporting role of performance measurement and management practice in the development of business relationships.

The practice and use of picuristes (lay injectionists) among Haitian immigrants in Miami -Dade County, Florida

This exploratory study examined use of picuristes among Haitian immigrants in Miami-Dade County, Florida. It describes how this health-seeking behavior is socially constructed among Haitian immigrants in terms of benefits. (b) risks, (c) sex, (d) gender, (e) acculturation proxies, and (f) transnational influences. It is conducted within the frameworks of Symbolic Interactionism, the Health Belief Model and the Explanatory Model of Illness. ^ Purposive sampling and a mixed-method design were used to obtain semistructured interviews of 10 picuristes and 25 users. The same methods were employed to select survey respondents so as to obtain a descriptive estimate of picuriste use and covariates of picuriste use within the sample. ATLAS.ti 5.0 and SPSS 14.0 were used to analyze the data. ^ The findings indicate an interconnection of elements from Vodou, traditional Haitian health beliefs and picuriste practice and use. ^ Rekonnèt, a relationship based on a history of trust with individuals related by blood or who share close personal and social ties was identified as a sufficient and necessary reason for picuriste practice and use. ^ Benefits reported are that the picuriste injections directly impact the blood, and that they represent affordable and convenient access to health care. Risks include rashes, abscesses and fevers. The reuse of injection equipment, routine injection of antibiotics and unknown substances and the improper discard of syringes and needles were reported, implying unrecognized risks of preventable infectious disease. No participant described a process that adheres to established international standards for safe injections. ^ There is no clear evidence that biological sex, gender, length of time in U.S. or language of interview influence picuriste practice or use. Transnational ties facilitate transport of substances from Haiti and the practice and use of picuristes locally. ^ Recommendation by a relative or trusted friend and believing that the benefits of picures outweigh risks were covariates of picuriste use. ^ This study highlights values and priorities of Haitian immigrants seeking healthcare, and cultural forces that shape their decisions about wellness and treatment. Future studies should test the application of Symbolic Interactionism to picuriste use in larger epidemiological studies that examine picuriste use in relation to health status.^

The Influence of Psychological Predictors and Cognitive Behavioral Stress Management Intervention on Antiretroviral Therapy (ART) Adherence Among HIV-Positive Female Haitian Alcohol Users

Purpose: Over half the HIV-infected persons in the Caribbean, the second most HIV-impacted region in the world, live in Haiti. Using secondary data from a parent study, this research assessed the effects of psychological and social factors on antiretroviral therapy (ART) adherence among Haitian, HIV-positive, female alcohol users. Theoretical Foundation and Research Questions: Using the Theory of Planned Behavior/Reasoned Action and the Information, Motivation, Behavior skills model as guiding theoretical frameworks, the study examined the effectiveness of an adapted cognitive behavioral stress management (CBSM-A) intervention in improving ART adherence. The effect of psychological factors (depression, anxiety, beliefs about medicine, and social support), social factors (stigma, relationship status, and educational attainment), and alcohol on adherence to ART was assessed. Methods: The sample consisted of 116 female ART patients who were randomly assigned to the CBSM-A intervention or the wait-list control group. Participants completed intervention sessions as well as pre- and post-test assessments. Analyses of variance, t-tests, and point biserial correlations were used to test hypotheses. Results: Surprisingly, ART adherence rates significantly decreased for both groups combined [F (1, 108) = 8.79, p = .004]; there was no significant difference between the intervention and control groups with regard to the magnitude of change between baseline and post assessment. On average, depression decreased significantly among participants in the CBSM-A group only [(t (62) = 5.54, p < .001)]. For both groups combined, alcohol use significantly decreased between baseline and post-assessment [(F (1, 78) = 34.70, p < .001)]; there was no significant difference between the intervention and control groups with regard to the magnitude of change between baseline and post-assessment. None of the variables were significantly correlated with ART adherence. Discussion: Adherence to ART did not improve in this sample, nor were any of the variables significantly associated with adherence. The findings suggest that additional supportive and psychological services may be needed in order to promote higher adherence to ART among HIV-positive females. More research may be needed on this sample; a focus on mental health issues, partner conflict, family and sexual history may allow for better targeting and more successful interventions.

The Immunomodulatory Role of Alcohol on HIV-Infected Monocyte-Derived Dendritic Cells

Alcohol is known to induce inflammation in the presence of the human immunodeficiency virus (HIV). In our previous studies, we revealed that alcohol induces cannabinoid receptors which play a role in the regulation of inflammatory cytokine production in monocyte-derived dendritic cells (MDDC). However, the ability of alcohol to alter MDDC function during HIV infection has not been clearly elucidated yet. To study the potential impact of alcohol on HIV-infected MDDC (confirmed by p24 ELISA), monocytes were isolated from commercially available buffy coats and cultured for 7 days with GM-CSF and IL-4. MDDC were infected with HIV- 1Ba-L and treated with different concentrations of alcohol (0.1% band 0.2%) for 4-7 days. MDDC phenotype, endocytosis, cytokine production, and ability to transmit HIV to T cells were analyzed. Uninfected CD4+ T cells were co-cultured for 7 days with either infected/treated MDDC or the supernatants from infected/treated MDDC. Inflammatory cytokine arrays were performed using supernatants from HIV-infected MDDC treated with alcohol. Results showed that HIV positive MDDC treated with alcohol had higher levels of infection compared to untreated HIV positive controls. CD4+ T cells exposed to HIV-infected MDDC acquired 100-fold higher levels of p24 compared to CD4+ T cells exposed to only supernatants. CD4+ T cells exposed to HIV-infected and alcohol-treated MDDC had higher levels of infection compared to controls. Cytokine array data show dysregulation of cytokine production by alcohol. In addition, MDDC phenotype and endocytic capacity were altered in the alcohol treated MDDC. Our results indicate a crucial role of MDDC in HIV transmission to T cells and provide insights into the inflammatory role alcohol exerts on dendritic cell function in the context of HIV infection. Supported by the National Institute on Alcohol Abuse and Alcoholism award R00AA021264, the National Institute on Drug Abuse award R01DA034547, and the Institute on NeuroImmune Pharmacology at FIU.

The Evolution of Pharmaceutical Care for Drug Misusers

This survey was funded by a grant from the Chief Scientist Office (CSO), Grant No: CZH/4/998.

The Evolution of Pharmaceutical Care for Drug Misusers

This survey was funded by a grant from the Chief Scientist Office (CSO), Grant No: CZH/4/998.