Stir bar sorptive extraction of diclofenac from liquid formulations: A proof of concept study

A new stir bar sorptive extraction (SBSE) technique coupled with HPLC-UV method for quantification of diclofenac in pharmaceutical formulations has been developed and validated as a proof of concept study. Commercially available polydimethylsiloxane stir bars (Twister (TM)) were used for method development and SBSE extraction (pH, phase ratio, stirring speed, temperature, ionic strength and time) and liquid desorption (solvents, desorption method, stirring time etc) procedures were optimised. The method was validated as per ICH guidelines and was successfully applied for the estimation of diclofenac from three liquid formulations viz. Voltarol (R) Optha single dose eye drops, Voltarol (R) Ophtha multidose eye drops and Voltarol (R) ampoules. The developed method was found to be linear (r=0.9999) over 100-2000 ng/ml concentration range with acceptable accuracy and precision (tested over three QC concentrations). The SBSE extraction recovery of the diclofenac was found to be 70% and the LOD and LOQ of the validated method were found to be 16.06 and 48.68 ng/ml, respectively. Furthermore, a forced degradation study of a diclofenac formulation leading to the formation of structurally similar cyclic impurity (indolinone) was carried out. The developed extraction method showed comparable results to that of the reference method, i.e. method was capable of selectively extracting the indolinone and diclofenac from the liquid matrix. Data on inter and intra stir bar accuracy and precision further confirmed robustness of the method, supporting the multiple re-use of the stir bars. (C) 2010 Elsevier B.V. All rights reserved.

A concept analysis of renal supportive care: the changing world of nephrology

Title. A concept analysis of renal supportive care: the changing world of nephrology

Aim. This paper is a report of a concept analysis of renal supportive care.

Background. Approximately 1.5 million people worldwide are kept alive by renal dialysis. As services are required to support patients who decide not to start or to withdraw from dialysis, the term renal supportive care is emerging. Being similar to the terms palliative care, end-of-life care, terminal care and conservative management, there is a need for conceptual clarity.

Method. Rodgers' evolutionary method was used as the organizing framework for this concept analysis. Data were collected from a review of CINAHL, Medline, PsycINFO, British Nursing Index, International Bibliography of the Social Sciences and ASSIA (1806-2006) using, 'renal' and 'supportive care' as keywords. All articles with an abstract were considered. The World Wide Web was also searched in English utilizing the phrase 'renal supportive care'.

Results. Five attributes of renal supportive care were identified: available from diagnosis to death with an emphasis on honesty regarding prognosis and impact of disease; interdisciplinary approach to care; restorative care; family and carer support and effective, lucid communication to ensure informed choice and clear lines of decision-making.

Conclusion. Renal supportive care is a dynamic and emerging concept relevant, but not limited to, the end phase of life. It suggests a central philosophy underpinning renal service development that allows patients, carers and the multidisciplinary team time to work together to realize complex goals. It has relevance for the renal community and is likely to be integrated increasingly into everyday nephrology practice.

Les deux André et le concept de la durée: André Chamson et André Malraux dans le même combat pour les valeurs spirituelles.

Les vies et les carrières d’André Chamson et d’André Malraux se ressemblent par de multiples aspects. Contemporains, ils se connaissaient bien, menaient souvent les mêmes combats, souffraient des mêmes préoccupations, Mais c’est surtout par rapport à l’esprit qui les animait, en tant que grandes personnalités marquantes du XXe siècle, que d’intéressants parallèles peuvent être établis entre eux, que nous pouvons avec profit examiner les valeurs universelles et spirituelles qu’ils promouvaient, valeurs emblématiques pour tant de penseurs, d’acteurs, et d’écrivains de ce siècle. Ainsi pourrions-nous par ailleurs interroger et même évaluer la solidité, la résistance et le potentiel de telles valeurs pour le siècle à venir.

Development of an egg hatch assay for the diagnosis of triclabendazole resistance in Fasciola hepatica: proof of concept.

The aim of this study was to develop an Egg Hatch Assay (EHA) test for the detection of triclabendazole (TCBZ) resistance in Fasciola hepatica. A number of fluke isolates were used, of differing sensitivity to TCBZ. Eggs were exposed to solutions of triclabendazole sulphoxide (TCBZ.SO) for 14 days, then triggered to hatch. Egg development was divided into 6 distinct and easily identifiable stages: dead, empty, unembryonated, cell division, eye spot and hatched. The number of eggs reaching those stages was recorded. Initially, the discriminating dose (1% hatch) was determined for the Cullompton isolate, used as TCBZ-susceptible (TCBZ-S) standard. Once this concentration had been resolved, the response of different isolates to this concentration was examined. The hatch rate of the Fairhurst isolate was not significantly different from that of the Cullompton isolate, confirming its TCBZ-S status. The Patagonia isolate has not been exposed to TCBZ in the field and should be TCBZ-S: the results of the EHA supported this. The egg hatch response of the Oberon and Dutch isolates differed significantly from that of the Cullompton isolate; the former isolates are regarded as TCBZ-resistant (TCBZ-R) and the results confirmed this. Another isolate, the Leon isolate, was originally described as being TCBZ-R, but has since been shown to be TCBZ-S. There was no difference in its response to TCBZ.SO in the EHA from the Cullompton (and Fairhurst and Patagonia) isolate(s), further indicating its TCBZ-S status. The impact of TCBZ.SO treatment on the component stages of egg development was determined and revealed differences between the isolates. In conclusion, the results of the study have shown that it is possible to discriminate between TCBZ-S and TCBZ-R isolates of F. hepatica on the basis of the response of their eggs to an EHA and the test could be used to evaluate the TCBZ sensitivity of unknown field isolates

Cough hypersensitivity syndrome is an important clinical concept:a pro/con debate

The major etiologies of chronic cough are generally accepted to consist of upper airway cough syndrome (formerly postnasal drip syndrome), eosinophilic airway inflammation (asthma, nonasthmatic eosinophilic bronchitis), and gastroesophageal reflux disease (GERD). However, only a small percentage of patients with these very common conditions suffers from chronic cough. Furthermore, acute cough due to viral upper respiratory tract infection (URI) is almost always a transient, self-limited condition, yet in a small subgroup of patients, URI heralds the onset of chronic, refractory cough. The cough hypersensitivity syndrome has been proposed to explain the occurrence of chronic cough in a subgroup of patients exposed to the same putative triggers as the vast majority of the population in whom chronic cough does not result. Although conceptually the cough hypersensitivity syndrome may be intellectually satisfying, differences of opinion remain as to whether this newly recognized entity is of clinical significance, i.e., useful for the treatment of patients suffering from chronic cough. The Third American Cough Conference, held in New York in June 2011, provided an ideal forum for the debate of this issue between two internationally recognized authorities in the field of cough.

A defeasible reasoning model of inductive concept learning from examples and communication

This paper introduces a logical model of inductive generalization, and specifically of the machine learning task of inductive concept learning (ICL). We argue that some inductive processes, like ICL, can be seen as a form of defeasible reasoning. We define a consequence relation characterizing which hypotheses can be induced from given sets of examples, and study its properties, showing they correspond to a rather well-behaved non-monotonic logic. We will also show that with the addition of a preference relation on inductive theories we can characterize the inductive bias of ICL algorithms. The second part of the paper shows how this logical characterization of inductive generalization can be integrated with another form of non-monotonic reasoning (argumentation), to define a model of multiagent ICL. This integration allows two or more agents to learn, in a consistent way, both from induction and from arguments used in the communication between them. We show that the inductive theories achieved by multiagent induction plus argumentation are sound, i.e. they are precisely the same as the inductive theories built by a single agent with all data. © 2012 Elsevier B.V.