The Medicines Use Review and Prescription Intervention (MUR) service was commissioned as part of the 2005 community pharmacy contract for England and Wales. The aim of the MUR service is to improve patients’ knowledge and use of medicines and to reduce avoidable medicines waste. MURs form part of a Government strategy that aims to improve patients’ adherence to medicines in order to optimise health gain and reduce cost associated with unused medicines. MURs are also seen as a ‘concordance review’ and pharmacy’s professional bodies acknowledge the service as a means to further the professional role of community pharmacists. However, it remains uncertain from studies investigating the outcomes of MURs, the extent to which the service is benefitting patients. One significant drawback to previous studies is the lack of in-depth investigation of the MUR consultation and the patients’ perspective of the service. This thesis provides valuable insights into what occurs during an MUR consultation and investigates the patient’s perspective of the service and that of the pharmacy staff. This work also explores whether the MUR policy aims are being realised in practice and translated into more effective use of medicines. Ten weeks of fieldwork observations were undertaken in two English community pharmacies. One-week placements were made over a 12-month period between November 2008 and October 2009. Observations were made of all pharmacy activities, including fifty-four MUR consultations. Thirty-four patients subsequently agreed to be interviewed about their experience of the MUR. Eight patients were observed to decline the offer of an MUR, of which three patients were interviewed about the reasons why they declined. After the pharmacy observations were completed, five pharmacists and twelve support staff interviews were held to discuss professional perspectives of MURs. The findings from this study suggest that the MUR service is a modern and developing service but one that remains unestablished. Patient awareness of MURs was poor and nearly all MURs were initiated by the pharmacist; no patients were referred from the GP. Pharmacy staff did not actively seek to recruit patients who may benefit most from an MUR and the majority were invited in ad hoc manner. Patients were given little time to consider whether to take part in an MUR and were insufficiently informed of their purpose or personal value. MURs were framed as a monitoring activity and most patients reported that the MUR did little to improve their knowledge of their medicines and rarely affected their use. They perceived their GP to have the main authority over their medicines. Patients considered that significant medicine-related problems would be best resolved by talking to the GP rather than with the pharmacist during an MUR. In effect, a supplier induced demand for MURs was observed. Nevertheless, all patients reported feeling comfortable speaking to the pharmacist during an MUR and most described the consultation in positive terms. Most patients viewed the pharmacist as a knowledgeable expert and some felt reassured about their medicines following an MUR. Observations of the MUR consultation revealed pharmacists were subordinate to the ‘technology’ of the MUR form and adhered to its ‘tick-box’ format. Pharmacists used predominantly closed questions which enabled the MUR form to be completed efficiently, but this forestalled wider discussion of the patient’s health and medicines. The MUR service was at odds with the intention to create a patient-centred service. When complex or indeterminate issues were raised, these were often circumvented or the patient referred to the GP. Pharmacists reported in their interviews that they welcomed MURs and the resultant potential to raise their profile with patients. However, they were unclear about what they wanted to advise during an MUR and how patients might gain maximum benefit from the review. They also reported concerns over patient recruitment, organisational pressures to pursue a target number of MURs and difficulties integrating MURs within their existing activities. MURs were pragmatically accommodated alongside existing duties without additional resource. Support staff reported feeling discomfort when they were left to explain to patients and customers why the pharmacist was absent during an MUR and described using various strategies and personal judgements to deal with waiting patients. This study has important implications for patients, professionals and policy makers. Patients should be aware that the MUR service is funded by the NHS and is available for them to use. More support from GPs is needed to identify patients who may most benefit from an MUR. This study highlights the need for consultation and communication skills training for pharmacists, so they are able to effectively elicit patient beliefs, concerns and preferences about medicines during the MUR. Organisations also need to reconsider the way they motivate pharmacists to undertake MURs to avoid unintended consequences for patient care. Policy makers should reconsider strategies that are based on rationalised policies as a means to improving patient adherence to medicines. Effective services need to be responsive to the patient’s individual circumstance and preference. Further research is needed into MURs in a wider and more diverse range of pharmacy settings in order to explore these issues further.

Supplying safe, appropriate and effective non-prescription medicines for customers in community pharmacies is a key role of pharmacists and pharmacy assistants in every country. However, in low and middle-income countries, including Vietnam, the quality of professional services from pharmacies is limited, unclear and has often been questioned. There is limited research about the real situation surrounding non-prescription medicine supply in community pharmacies in Vietnam. The factors that influence the supply of non-prescription medicines to customers and to what extent the service provision could be improved for the benefit of pharmacy customers needs to be explored. This study aimed to investigate non-prescription medicines supply in community pharmacies in Hanoi, Vietnam in order to provide scientific evidence about the situation. A mixed method approach was used in this study to provide valuable insights into what occurs during pharmacy staff-customer transactions. Following ethical approval, fieldwork observations were undertaken in five community pharmacies over a five week period from March to May 2011, this was followed by 22 semi-structured interviews with eight pharmacists and 14 pharmacy assistants who had been observed. The interviews enabled participants to express their perceptions and experiences regarding the supply of non-prescription medicines to customers in community pharmacies. Survey research, using a structured questionnaire, was conducted with 505 pharmacy customers who were asked to evaluate the pharmacy service that they had just received. Results from the three sources were triangulated and validated by comparing, contrasting, complementing and confirming in order to provide a better understanding of non-prescription medicines supply and make recommendations for improving the service provision in community pharmacies in Vietnam. The findings from this study indicate that factors influencing the supply of non-prescription medicines in community pharmacies include attitudes of pharmacy staff, their medical and pharmaceutical knowledge and their communication skills. The influence of the pharmacy settings, customer factors such as customers’ complex and diverse demands, the irrational use of medicines, using medicines following the suggestions of others, and tough customers were all factors that impacted on staff-customer transactions. Being conveniently located, the pharmacy offering reasonably priced medicines and being a large pharmacy with a good reputation were also considered important impacting on customer selection of community pharmacy. The results of this research show that there are limitations in pharmacy service provision and there is a discrepancy between pharmacy staff perceptions and actual practice in terms of attitudes. Poor performance, in many situations, did not come from a lack of knowledge; rather it appeared to result from the negative attitudes of pharmacy staff. Such negative attitudes of pharmacy staff are likely to be related to their focus on just short-term profit rather than focusing on a balance between short-term and long-term benefits for both customers and pharmacies. Positive attitudes, taking greater responsibility, customer loyalty and long-term benefits were ignored. Poor performance of pharmacy staff, to some extent, was also affected by their education and training. Some educational organisations have commercialised their training activities and paid too much attention to the quantity of graduated students rather than the quality of their education and training. This study has important implications for the improvement of the responsible supply of non-prescription medicines in community pharmacies in Vietnam including the identified needs for attitude interventions and training. New subjects should be added to the pharmacy students’ curricula and training should be developed for pharmacy assistants in areas such as communication skills, customer psychology, selling skills and patient safety. For pharmacists and pharmacy assistants, gaining treatment experience from customers’ feedback and keeping up to date with new information should be a continuous activity. Close co-operation between health authorities, policy makers and researchers needs to be developed in conducting further research and implementing appropriate policies, in order to improve the service provision in community pharmacies in Vietnam.

The formation of three-dimensional (3D) models for tissue engineering purpose provides a more conducive environment to enable complex biological interactions and processes between cells, biomaterials and bioactive molecules. Microparticles (MP) can be used as supporting matrix for 3D construct in cells and a carrier to deliver bioactive agents for cell development and differentiation, particularly for bone tissue engineering. Poly(glycerol adipate) (PGA) is a potential polymer for tissue engineering purposes as it is biodegradable and has biocompatibility with several cells. The aim of this study is to modify PGA polymer for MP with well-defined properties for drug encapsulation and release, promote cell-MP interaction and evaluate the osteogenic differentiation with MP incorporation in mouse embryonic stem (mES) and osteoblast cells. The PGA polymer has been modified by substituting 40% pendant hydroxyl groups onto the polymer backbone with stearoyl (C18) groups to increase encapsulation efficiency of drug within MP. Further modification was tethering one carboxyl terminus in PGA polymer with maleimide-poly(ethylene glycol) (MIHA-PEG-NH2) linker for ligand attachment on the surface of MP. Collagen, as a ligand, was modified by attaching iminothiolane to give a functional thiol group for interaction with maleimide group on the surface of 40%C18-PGA-PEG-MIHA MP. The microparticles were prepared using an emulsification method. Dexamethasone phosphate (DXMP) and simvastatin (SIM) were encapsulated within the MP. The MP-cell aggregate formation was evaluated as well as cell metabolism activity. The effect of polymer modification on drug release from MP was evaluated in the cells by analyzing osteogenic differentiation in cells. The MP prepared from modified PGA polymer exhibited high encapsulation efficiency of SIM in MP. By adjusting the formulation parameters, the release of SIM from MP could be extended to 21 days. The collagen attachment on the surface of 40%C18-PGA-PEG-MIHA MP promoted cell metabolic activity and produced more extensive markers related to osteogenic differentiation.

Following the stability analysis, a testing protocol was devised and the legal and ethical obligations of the pharmacist in the addition of drugs to PN considered

In order to investigate further the mode of action of these compounds, synthesis of proteomic probes was attempted. Synthetic design and attempts are presented chapter VII. To establish whether there was 24-SMT present in the blood stream form of T. b. brucei, a Northern blot was carried out. This confirmed transcription of the enzyme which was then cloned, over expressed and purified (Chapter VIII). Enzyme assays were carried out against the recombinant enzyme.

A dissertation submitted in partial compliance with the requirements for the Master's Diploma in Technology: Homoeopathy, Technikon NataI, 1994. / The efficacy of Pilocarpus Jaborandi in the management of emotional palmar hyperhidrosis was studied. It was hypothesised that this homoeopathic drug would cause a significant decrease in sweat production rates. The study was double blinded and consisted of thirty treated patients, with fifteen patients in group and fifteen patients in the the placebo group. Patients were chosen by convenience sampling with no specifications of age or sex. The treated group received Pilocarpus Jaborandi 9 CH, and were instructed to take five pills on waking everyday for ninety days. The other group received a placebo also for ninety days. Quantification of the first day, on ninetieth day of sweat production was done on the forty-fifth day and treatment, by means of on the sweat collection tests. In each test sweat was / M

Malaria continues to pose a significant global health and socio-economic burden on those regions where it is endemic. Despite substantial investment in the delivery of artemisinin-based combination therapies, causing a fall in malaria mortality, recent data suggest that this parasitic disease still imposes a significant impact. A major problem is the narrow drug discovery pipeline, made worse by reports of artemisinin resistance. In recent years, high-throughput screening of natural products derived from plants and marine organisms has led to the discovery of potent anti-malarial indole alkaloids (such as dihydrousambarensine), many of which contain an indoloisoquinoline core. Building on previously discovered methodology in our group, we have developed a series of novel, enantiomerically pure, synthetic indoloisoquinoline and their potential as anti-malarial leads was assessed. The structure-activity relationship of these compounds was investigated in several areas and a lead compound was generated with an activity close to that of a known anti-malarial natural product dihydrousambarensine.

Tesis para optar al grado de Magister en Filosofía mención en Axiología y Filosofía Política. / Quien observe el estado actual de la medicina no dejará de sorprenderse con la importancia, y la velocidad, de una inusitada corriente de modificaciones que abruman el convencional trato entre médicos y pacientes. Baste pensar, por ejemplo, en los actuales e intrusivos sistemas de seguros de salud; en sus frías fórmulas administrativas, usadas para medir y abaratar la curación; como en los eficaces y sofisticados procedimientos de tecnología médica; etc. Tal parece que todos estos cambios se hubieran acentuado a partir de mediados del siglo XX, llegando a constituirse en una suerte de desafío para la actual definición de “arte y ciencia de curar”. En ese sentido, no cabe sino colocarle más atención al problema, porque bien podría tratarse del nacimiento de un nuevo imperativo productivo para la salud. Especialmente si se considera que esta evolución estaría vinculada a la consolidación de una forma diferente de vida social, más masificada, tecnológica y economicista (J.Millas, 1962, p.31).

Submitted in partial compliance with the requirements of the Master’s Degree in Technology: Homoeopathy, Durban University of Technology, Durban, South Africa, 2016. / Aim The purpose of this research study was to compare the similarity and differences of the rubrics from a proving of a homoeopathic complex (Cinnabaris 12CH, Hydrastis canadensis 12CH and Kalium bichromicum 12CH) in order to establish whether the symptoms are similar to the individual constituents, or whether a new remedy is produced when individual remedies are combined. The research questions addressed by the study were: 1) Will the twelfth centesimal potency (12CH) of the homoeopathic complex produce clearly observable signs and symptoms in healthy provers? 2) Will the majority of signs and symptoms of the complex be similar to those of its constituent parts? Methodology The proving was a randomised double blind placebo controlled study involving 20 participants who met the inclusion and exclusion criteria. The provers were randomly assigned to either a verum (80%) or placebo group (20%). Provers recorded their symptoms in their journals for one week prior to administration of the proving complex in order to establish a baseline for comparison. The proving complex was in form of lactose granules dispensed in lactose powders. Provers were given six lactose powders, one powder to be taken sublingually three times a day or until symptoms occurred. The provers recorded all mental or physical symptoms experienced in their journals. Once the proving was completed the journals were collected and symptoms derived from the recordings were collated and analysed. This information was converted to materia medica and repertory format. The researcher then analysed each rubric in order to establish if any or all of the three remedies of the complex appeared in that rubric. This comparison reflected the number of rubrics that contained the individual remedies of the complex. In this way the researcher established the rubrics that were unique to the complex as a whole. vi Results A total of 337 rubrics were produced by the proving. The analysis of rubrics showed that 216 rubrics did not contain any of the three remedies; 72 rubrics contained at least one of the three remedies; 29 rubrics contained two of the three remedies; and 20 rubrics contained all three remedies. Eighteen new rubrics were identified. In analysing the symptoms elucidated, a definite polarity between symptoms was noted, including within the same prover. This was the case with mental and physical symptoms. A vast range of symptoms was produced, spanning 29 sections of the repertory, with the majority being physical, related to headaches were quite common amongst provers, pain in the abdominal region, pain in the extremities, eye symptoms such as lachrymation and pain, pain in the throat, chest and neck, skin eruptions. Sinusitis or rhinitis symptoms such as nasal itching, sinus congestion, nasal discharge and sneezing were observed. A significant change in appetite and thirst was seen. The main regions that had an affinity for the complex were the head, abdomen and extremities with pain as the main symptom. Conclusion The substance did produce signs and symptoms in the provers, so Research Question 1 was answered with a “Yes”. Only a small proportion (0.05%) of the rubrics from the proving contained all three constituent remedies, therefore Research Question 2 was answered with a “No”. The results show that although the proving symptoms shared a small degree of similarity to the constituent remedies, the complex as an entity formed its own individual picture. / M

Folate uses the natural endocytosis pathway via the folate receptor (FR) to enter the cells. Folate conjugation to small or macromolecular therapeutics has hence been exploited for intracellular delivery to, particularly, cancerous cells. This work reports on the expression and functionality of FR in polarised cell monolayer models of respiratory and gastrointestinal mucosa with the view to assess its potential for delivery of folate-modified macromolecular therapeutics either intracellularly or across the epithelium. Four cell lines representing bronchial and intestinal epithelium; cancer-derived intestinal Caco-2 and bronchial cell line Calu-3, and noncancerous intestinal and bronchial cell lines IEC-6 and HBEC were cultured on permeable membranes to produce polarised monolayers. Expression of FR was confirmed by RT-PCR and Western blot analysis for all the tested cell types and shown to be dependent on culturing time. The functionality of the receptor for endocytosis was demonstrated by a model macromolecular folate conjugate (fluorescent ovalbumin-folate (OVA-FA)), whereby significantly higher cellular uptake of the folate-conjugate, relative to non-folate control, was clearly demonstrated. Importantly the data showed that the expressed folate receptor was capable of mediating transport of the macromolecular folate conjugate across (transcytosis) the cells in the polarised monolayers. Preliminary studies led to investigation of the folate mediated uptake and transport of folate modified nanoparticles (NPs). It was shown that folate modified NPs traversed the Calu-3 layers and studies characterizing this transport indicated folate involvement in this process. Adsorption of OVA-FA on the surface of NPs was seen to promote their cellular uptake and transport across the cell layers. To examine the mechanism of cellular uptake and transport of folate modified nanoparticles, various endocytic inhibitors were employed. The study demonstrated an involvement of the caveolar pathway in internalization of folate modified nanoparticles; as judged from a significant reduction of internalization in filipin (inhibitor of caveolar pathway) treated cells. Moreover, the work also showed evidence of transport of folate-modified nanoparticles via the caveolar pathway, since translocation of nanoparticles across the cell monolayer was absent when this path was inhibited. Disruption of actin filament and microtubules caused no difference in cellular uptake of NPs but increased the transcytosis of folate modified NPs. Confocal microscopy, Transmission Electron Microscopy (TEM), Total Internal Reflection Microscopy (TIRM) and Total Internal Reflection Florescence microscopy (TIRFM) were used to confirm and visualize quantitative data. This study also investigated the effects of surface ligand distribution pattern (ligand clustering and density) on the internalization of nanoparticles by Calu-3 cells cultured as polarised layers. The density of the displayed ligand was manipulated by controlling the conjugation level of folate-ovalbumin, while ligand clustering was achieved by co-adsorption of varying mixtures of folate-ovalbumin conjugate (at different ligand density levels) and unconjugated ovalbumin. Increasing ligand density on the nanoparticle surface resulted in increased internalization of modified nanoparticles by the cells, up to a saturation level. Surface ligand density also affected the cellular uptake pathway; from predominantly clathrin to predominantly caveolae-mediated as the ligand density was increased. It was further demonstrated that surface clustering of the folate ligand enhanced cellular internalization of nanoparticles, relative to its dispersed surface distribution.