Dissertations / Theses on the topic 'Quality use of medicines'

There has been an upsurge in the use of Complementary and Alternate Medicines (CAMs) in both developed and developing countries. Although herbal medicines have been in use for many centuries, their quality, safety and efficacy are still of major concern. Many countries are in the process of integrating CAMs into conventional health care systems based on the knowledge and use of traditional medicines. The quality control (QC) of herbal products usually presents a formidable analytical challenge in view of the complexity of the constituents in plant material and the commercial non-availability of appropriate qualified reference standards. Sceletium, a genus belonging to the family Aizoaceae, has been reported to contain psychoactive alkaloids, specifically mesembrine, mesembrenone, mesembrenol and some other related alkaloids. Sceletium is marketed as dried plant powder and as phyto-pharmaceutical dosage forms. Sceletium products and plant material marketed through health shops and on the internet are associated with unjustified claims of specific therapeutic efficacy and may be of dubious quality. Validated analytical methods to estimate Sceletium alkaloids have not previously been reported in the scientific literature and the available methods have focused only on qualitative estimation. Furthermore, since appropriate markers were not commercially available for use as reference standards, a primary objective of this study was to isolate relevant compounds, qualify them as reference standards which could be applied to develop appropriate validated qualitative and quantitative analytical methods for fingerprinting and assay of Sceletium plant material and dosage forms. The alkaloidal markers mesembrine, mesembrenone and ∆⁷ mesembrenone were isolated by solvent extraction and chromatography from dried plant material. Mesembranol and epimesembranol were synthesised by hydrogenation of the isolated mesembrine using the catalyst platinum (IV) oxide and then further purified by semi-preparative column chromatography. All compounds were subjected to analysis by ¹H, ¹³C, 2-D nuclear magnetic resonance and liquid chromatography-tandem mass spectroscopy. Mesembrine was converted to hydrochloride crystals and mesembranol was isolated as crystals from the hydrogenation reaction mass. These compounds were analysed and characterised by X-ray crystallography. A relatively simple HPLC method for the separation and quantitative analysis of five relevant alkaloidal components in Sceletium was developed and validated. The method was applied to determine the alkaloids in plant material and dosage forms containing Sceletium. An LCMS method developed during the study provided accurate identification of the five relevant Sceletium alkaloids. The method was applied for the quantitative analysis and QC of Sceletium plant material and its dosage forms. This LCMS method was found to efficiently ionize the relevant alkaloidal markers in order to facilitate their detection, identification and quantification in Sceletium plant material as well as for the assay and QC of dosage forms containing Sceletium. The chemotaxonomy of some Sceletium species and commercially available Sceletium dosage forms were successfully studied by the LCMS method. The HPLC and LCMS methods were also used to monitor the bio-conversion of some of the alkaloids while processing the plant material as per traditional method of fermentation. Additionally a high resolution CZE method was developed for the separation of several Sceletium alkaloids in relatively short analysis times. This analytical method was used successfully to fingerprint the alkaloids and quantify mesembrine in Sceletium and its products. Sceletium species grown under varying conditions at different locations, when analyzed, showed major differences in their composition of alkaloids and an enormous difference was found to exist between the various species with respect to the presence and content of alkaloids. Sceletium and its products marketed through health shops and the internet may thus have problems with respect to the quality and related therapeutic efficacy. The QC of Sceletium presents a formidable challenge as Sceletium plants and products contain a complex mixture of compounds. The work presented herein contributes to a growing body of scientific knowledge to improve the QC standards of herbal medicines and also to provide vital information regarding the selection of plant species and information on the specific alkaloidal constituents to the cultivators of Sceletium and the manufacturers of its products.

Improving the quality use of medicines (QUM) among seniors, particularly those using multiple medicines, is a national priority. The National Prescribing Service??s Seniors QUM Program was developed in collaboration with consumers to address seniors?? medicines information needs. Seniors are trained as peer educators to convey QUM messages to other seniors in a single group session. However, there is a dearth of research assessing peer education for seniors about medicines, and little understanding of what peer educators do in practice. This research investigated how peer educators empower seniors toward the quality use of their medicines. A participatory action research inquiry was undertaken nationally with organisational leaders and locally with peer educators. The design was a nested case study with multiple sites, where the Seniors Program was the overarching case containing eight disparate local sites. The participatory inquiry engaged peer educators from each local site. Qualitative data were collected through participant observation and interviews. Data were analysed using grounded theory methods and findings were triangulated with other data sources. Peer educators demonstrated five main functions in the program ?? one primary function within QUM sessions and four support functions outside of sessions. The primary function of facilitating peer learning comprised 10 elements. A model depicts these elements in the context of varying session conditions and consequences. Educators?? lived experience as seniors and lay persons was an overarching contributor to peer learning, used strategically through storytelling to assist other elements. Sharing QUM outside of sessions occurred frequently, but requires development to reach isolated seniors. Peer educators exceeded expectations in getting QUM messages to seniors, applying unique skills to the information exchange within sessions. Their status as lay persons tackling the complex topic of QUM reflected an understanding of the disempowerment seniors may feel when seeking information about medicines. Peer educators?? ability to model an active partner role by applying their lived experience through storytelling in an interactive, mutually sharing session challenged seniors to rethink their medicines management and interactions with health professionals. As the population ages and medicines use increases, understanding and using seniors effectively as educators has great potential.

Young adult women in their first and second year of college are a group more commonly impacted by health-related concerns associated with condom use. Due to lack of consistent condom use and the increase in sexual partners, STIs remain an epidemic. Various types of studies have been conducted to investigate condom use among women college students. One factor that may influence condom use is the partner relationship. The literature on safe sex practices shows a gap regarding relationship quality and its potential influence on condom use. Guided by the Fletcher et al. model and Sternberg's triangular theory of love, the goal of this study was to explore whether the likelihood of using condoms is influenced by relationship quality components. Using a sample of 85 women college students, relationship quality was examined using the Perceived Relationship Quality Components Inventory. Using a binary logistic regression model, no statistically significant associations among relationship satisfaction, commitment, intimacy, trust, passion, love, overall relationship quality and condom use were found. The findings in this study confirm the existing knowledge, that is, condom use trends and behaviors among young college women remain unpredictable. Limitations to the study include a small sample size, age of majority in Nebraska, and failure to screen for important demographics. For the future, longitudinal studies would offer insight into how condom use behaviors vary depending on fluctuations in relationship quality. This study has implications for positive social change: It suggests an emphasis on a relationship-focused approach to condom use behaviors when working with freshman and sophomore college women.

Existem vários métodos para medir tipo e grau de uso de medicamentos. Esse estudo teve como objetivo caracterizar a prescrição médica para idosos, por meio de indicadores, em diferentes ambientes de atendimento à saúde em 4 municípios do Rio Grande do Sul. Buscou-se caracterizar a prescrição em locais de formação e atuação universitária, estabelecendo a prevalência de intervenções nãofarmacológicas e farmacológicas em prescrições para idosos, avaliando diferentes indicadores quanto a sua aplicabilidade em idosos e realizando inferências em relação ao uso racional de medicamentos. Fizeram parte do estudo serviços de atenção básica em saúde, além daqueles de média e alta complexidade, vinculados a ambientes de formação universitária na área da saúde, no sul do Brasil. A amostra foi constituída por prescrições médicas, obtidas diretamente dos pacientes, em nível de atenção primária em saúde e ambientes de média complexidade, ou por meio de prontuários hospitalares, durante o período de um ano. Para caracterização dos idosos, foram considerados aqueles com idade igual ou superior a 65 anos. A coleta de dados foi realizada ao longo de doze meses, em semanas, dias e turnos definidos por meio de sorteio. sorteio. Como resultados, observou-se que, nos ambientes de atenção básica em saúde e nos ambientes de média complexidade estudados, os idosos do Rio Grande do Sul apresentaram maior média de medicamentos prescritos e prevalência considerável de medicamentos inapropriados, em comparação com outros estudos que envolveram dados da população em geral em outros estados do país. Em contrapartida, esses idosos receberam menor percentual de prescrições com antimicrobianos e baixo percentual de prescrições com agentes injetáveis. As classes de medicamentos mais comumente prescritas no ambiente ambulatorial foram aquelas de uso contínuo, provavelmente em função das enfermidades crônicas apresentadas por pacientes desta faixa etária. Destacaram-se os fármacos que agem no sistema cardiovascular, no sistema nervoso e no trato gastrintestinal e metabolismo. Por sua vez, na internação de idosos nos hospitais estudados, independentemente de município, sazonalidade, gênero ou faixa etária mais avançada, identificou-se um perfil elevado de utilização de medicamentos, com polifarmácia (n=345, 85,4%) e prescrição de medicamentos inapropriados (n=325, 80,4%) em número significativo de idosos. Os medicamentos que mais apareceram nas prescrições hospitalares foram aqueles prescritos sob regime de demanda (se necessário). A prescrição inadequada aos idosos é frequentemente atribuída à falta de treinamento de uma equipe especializada em geriatria e gerontologia, além da deficiência da formação universitária. Nesse sentido, considerando-se o contexto demográfico e epidemiológico brasileiro e a caracterização da prescrição para o paciente idoso realizada no estudo, é importante priorizar ações multidisciplinares relacionadas a promoção, prevenção e recuperação de enfermidades e padronizar procedimentos, para evitar erros de prescrição, transcrição e dispensação. A educação continuada dos profissionais da área da saúde, a divulgação e a atualização de listas de medicamentos essenciais e das listas de medicamentos inapropriados para idosos podem ser ferramentas úteis para a qualificação da prescrição e a promoção do uso racional de medicamentos em idosos. A partir dos pontos vulneráveis da prescrição para idosos que foram levantados, podem ser estabelecidas mudanças nos ambientes de formação em saúde estudados, visando a construção de um perfil profissional que paute suas ações pela comunicação efetiva, interdisciplinar e compromisso social.
There are several methods to measure type and degree of drug use. This study aimed to characterize the prescription for the elderly by means of indicators in different environments of health care and 4 cities of Rio Grande do Sul. It was characterized the prescription in academic and training environments, establishing the prevalence of non-pharmacological interventions and pharmacotherapy prescriptions for the elderly, assessing the applicability of different indicators to the elderly prescriptions, and making inferences about the rational use of medicines. Participants of the study were elderly people attended in primary health care services and in medium and high complexity health care services, linked to universities located in the south of Brazil. The sample consisted of prescriptions obtained directly from patients, at the level of primary health care and environments of medium complexity, or through hospital records, during the period of one year. It was considered elderly patients those with age over 65 years. Data collection was conducted over twelve months, in weeks, days and shifts defined by lot. It was observed that in primary health care and medium complexity services the Rio Grande do Sul elderly prescriptions had a higher mean number of medications and a considerable prevalence of inappropriate medications, compared to other studies involving data from the general population. However, these elderly received a lower percentage of prescriptions with antibiotics and injectable drugs. The classes of drugs most commonly prescribed in the outpatient setting were those of continuous use, probably due to the chronic diseases that frequently occurred in the old age. Those classes involved drugs that act on the cardiovascular system, nervous system and gastrointestinal tract and metabolism. In the hospitals studied, independently of the city, seasonality, gender or older age, it was identified high profile drug utilization, with polypharmacy (n = 345, 85.4%) and inappropriate prescription of medications (n = 325, 80.4%) in great number of elderly. The drugs that most appeared in the hospital prescriptions were those prescribed under the demand scheme ("if necessary"). Inappropriate prescribing for the elderly is often attributed to the lack of training in geriatrics and gerontology and disability of university education. Considering the Brazilian epidemiological and demographic context and the prescription pattern for the elderly observed in this study, it is important to prioritize disciplinary actions related to the promotion, prevention and recovery from illness and standardize procedures to avoid errors in prescribing, transcribing, and dispensing. The continuing education of professionals in the health, distribution and update of essential drugs lists and use of lists of inappropriate drugs for elderly may be useful tools for the improvement of the prescription and promotion of rational drug use in the elderly. Based on the vulnerabilities of the prescription for the elderly that have been raised, it is possible to establish changes in the studied healthy education environments, aiming to build a professional profile that bases its actions on effective communication, interdisciplinary and social commitment.

The research programme focuses on Total Quality Management adoption and application. TQM which is established in a number of businesses and industries has more recently been introduced into healthcare. TQM definition and eclectic paradigm has been developed and tested for establishing quality performance and distinguishing radical change and continuous improvement approach. A number of critical elements and variables concerning implementation and application are identified which pertain to organisations which through size and bureaucracy operate with diverse missions, a wide range of systems and are characterised by degrees of rigidity from an employee mix of multiple knowledge, understanding competences skills and hence commitment. Research was conducted in healthcare provider organisations, which involved eighty-three NHS hospitals/Trusts, wherein two pilot, twelve TQM demonstration and sixty-nine sites were involved. The main focus concerned a case study Trust, which although demonstrating keen interest in quality management had not reached the formative stages of developing TQM definition or paradigm. The research framework is based on a number of approaches in that methods selected for evaluation were appropriate both to the situation and the context of TQM strategies being examined. Intention was to identify successes and failures of the TQM processes applied, establish similarities and distinguishable differences and determine extent to which TOM objectives were achieved and the impact of the processes on specific groups. The investigation was undertaken using longitudinal analysis which involved in-depth interviews with top managers and clinicians and a mix of employees, customers, potential customers and purchasers in the form of managers, consultants, hospital doctors, nurses, support services personnel, patients, members of the public and GPs. TOM Awareness and Action Seminars and Workshops involving personnel from a variety of international healthcare organisations provided an additional source of data. Self-completion questionnaires were also used. Data analysis compares and contrasts varying TQM models, processes, activities and results from degree of emphasis placed on critical elements and variables. Stage predictions and resulting outcomes are presented and quality of care improvements suggested from analysis of customer perceptions of quality and value. The findings show significant variations in approach between the hospitals/Trusts in matters which concern organisation, management and culture issues, resulting in a high proportion viewing TOM process as evolution from quality assurance to radical change, hospital process re-engineering and patient focused care A minority only included such processes in their application of TQM. Key conclusions result from attempt at establishing some measure of success and failure from TQM implementation and application. Findings contribute to the extant literature specifically in that beyond top management and clinician commitment to high level strategic focus is a combination of facilitator-led culture change, motivation and shared values directing attention to exceeding that of merely doing enough for reducing poor quality and customer complaints. Patient involvement in TOM is more problematic than literature suggests from both the patients and professionals perspectives of patient empowerment. Bottom-up action focused TQM paradigm working simultaneously with top down support and commitment requires barrier breaking, culture transformation and the establishment of internal/external customer and supplier chains and seeking to establish opportunities for continuous improvement and radical change in advance of attempts at in-depth implementation and evaluation. It is not over-statement to conclude that the majority of managers and clinicians were unaware of the costs of getting things wrong. Despite TOM being acted upon as driving force for competition most had limited knowledge of how much non-quality cost them, suggesting that they had not earlier thought it necessary to measure the costs of none or low quality. Research results, irrespective of applications definition or paradigm, question the views that TQM is long-term process. Whether these may be concluded as desire to integrate TOM with other foci or vacuum sucking in panaceas was unclear. It was clear however that although quality in healthcare is sacred total quality management is not.

People living in rural America face unique social circumstances that can prevent them from reaching optimal health status. This fact holds especially true in the rural Appalachian region of the United States where income, education, living circumstances, and lack of resources create an environment that has some of the highest rates of morbidity and mortality in the country. While the rest of the country has seen improvement in many health behaviors and health outcomes, rural Appalachian communities remain unchanged and further behind other regions. In many cases, programming and policy have failed to create a culture of health in Appalachia. Social determinants of the area should be included in interventions and this practice is imperative to achieve effectiveness. This study examined the social context and definitions of health in a rural, Appalachian community using the Social Quality Theory as a guiding framework. A community-based participatory research approach was adopted and implemented through the use of focus groups. The study generated many meaningful findings. It not only provided a new framework, but also provides an examination of how a rural, impoverished community lacks the social infrastructure to improve health. Current perceptions of health are limited to thoughts of disease or illness and overshadowed by negative social norms. There are few social resources currently available to improve health and a large presence of cultural impediments. Yet this “culture” also provides some advantages and assets that the community may leverage for change.

Eosinophilic oesophagitis (EoE) is a rare antigen-driven inflammatory gastrointestinal disorder characterised by oesophageal dysfunction, elevated levels of eosinophils in the oesophageal mucosa, and gastrointestinal symptoms. EoE incidence and prevalence is increasing rapidly. EoE Incidence peaks in late childhood and healthcare utilisation amongst children with EoE is high. This study provides the first known research into carer experiences and perspectives on healthcare utilisation, including complementary medicine (CM) use, treatment burden, and impact on health-related quality of life (HRQoL) for children with eosinophilic oesophagitis (EoE) and their carers for paediatric EoE in Australia. Methods: A national cross-sectional online survey was conducted in Australia between 5th September 2018 and 28th February 2019. The survey instrument incorporated preexisting validated tools along with other adapted survey items. The 149-item survey instrument included 42 core items and a further 107 items controlled by adaptive survey logic across five domains: socio-demographics; health service and treatment utilisation; CM use; financial support; and HRQoL for the child and the carer. Convenience and snowball sampling were employed to achieve a sample broadly representative of the paediatric EoE population in Australia. Study participants were carers of children (aged 18 years and under) with endoscopy-confirmed diagnosis of EoE. Data were presented as descriptive statistics (frequencies, percentages and means). Univariate relationships were analysed using chi square tests, Cramer’s V, linear regression and one-way analysis of variance analysis. Multivariate relationships were examined using various regression analytic methods including linear and logistic backwards stepwise regression, binomial logistic regression, and poisson regression. Cronbach’s alpha was calculated to determine the internal reliability of the Bakas Caregiving Outcomes Scale© for this study. Results: The survey was completed by 181 carers (mother, 96.6%) of an EoE child. Most children (91.2%, n=165) had seen a medical doctor and many had consulted with a CM practitioner (40.3%, n=73) for their EoE. Pharmaceuticals (n=156, 86.2%) were the most commonly used treatment option, followed by dietary changes (n=142, 78.5%), CM products (n=109, 60.2%), and CM therapies (n=42, 23.2%). Most children received care from numerous practitioners on multiple occasions, while more than half of carers (n=86, 56.2%) reported reduced HRQoL since their child’s diagnosis. Reported mean annual out-of-pocket expenditure for health-care utilisation (practitioner visits and treatment) was AUD$3064.3. Reduced ability to manage on income and missing more than one workday in the previous 30 days were significant predictors of lower carer HRQoL. Ability to manage on the current income described as “difficult some of the time”, “difficult all of the time”, and “impossible” were associated with lower child HRQoL. When compared with EoE diagnosis between 13 and 23 months old, diagnosis between two and four years old was a significant predictor of lowered child HRQoL. One-hundred sixty-five (91.2%) carers indicated they had utilised some form of CM for themselves and 125 (75.8%) of the carers using CM also reported using CM for their child’s EoE. Use of CM in children was more likely amongst children who had used a pharmaceutical for their EoE, and those whose carer had consulted with ‘other health practitioners or health workers’ for their child’s EoE or had consulted with a chiropractor for themselves. Conclusions: Paediatric EoE in Australia is associated with reduced HRQoL of children with EoE and their carers and significant treatment burden for carers. Further attention is required to identify ways to reduce treatment-related burden and improve the quality of life of both the carer and child. There is high CM use and substantial concomitant use of conventional medicines by children with EoE, despite no evidence for the safety and efficacy of the CM treatments commonly used. There is also the potential for complications from drug-herb and drug-nutrient interactions from using both conventional and CM treatments. Recommendations based on this research include better information for both clinicians (e.g. clinical guidelines, training) and carers (e.g. print and online information), improved care coordination and support services, and further research focusing on the safety and effectiveness of commonly used conventional and CM treatments and carer circumstances and beliefs related to caring for children with EoE.
Thesis (Masters)
Master of Medical Research (MMedRes)
School of Medical Science
Griffith Health
Full Text

Thesis (MScMed)--Stellenbosch University, 2008.
ENGLISH ABSTRACT: Introduction: Flow cytometry has progressively replaced many traditional laboratory tests due to its greater accuracy, sensitivity and rapidity in the routine clinical settings especially clinical trails. It is a powerful tool for the measuring of chemical (the fluorochrome we add) and physical (size and complexity) characteristics of individual cells. As these instruments became major diagnostic and prognostic tools, the need for more advanced quality control, standardized procedures and proficiency testing programs increased as these instrumentations and their methodology evolve. Minor instrument settings can affect the reliability, reproducibility and sensitivity of the cytometer and should be monitored and documented in order to ensure identical conditions of measurement on a daily basis. This can be accomplished by following an Internal Quality Assurance (IQA) and/ or External Quality Assurance (EQA) program. Currently there are no such programs available in South Africa and poorer Africa countries. HIV is a global concern and the laboratories and clinics in these places are in need of such IQA programs to ensure quality of their instrumentation and accurate patient results. Quality assurance programs such as CD Chex® and UK Nequas are available but due to bad sample transport, leave the receiving laboratories with nightmares. It would be best if there was a laboratory in South Africa that could provide the surrounding laboratories with stabilized whole blood samples that can be utilized as IQA. The transport of these samples can be more efficient due to shorter distance and thus the temperature variations limited. Aims and Objectives: The aim of Chapter one is to familiarize the reader with general terminology and concepts of immunology. Chapter two describes in detail the impact stabilized whole blood had on clinical immunology concerning Quality Control and Quality Assurance. The objective of this study is to stabilize whole blood with a shelf life of greater than 30 days to serve as reference control material for South African Immunophenotyping. It is further an objective to use these in-house stabilized control samples for poorer African countries as Internal Quality Assurance reference material. It is a still further objective to stimulate various lymphocyte subsets to express activation antigens and then stabilize these cells for more specialized immunological test and can serve as a QC for those required samples. Study design: In Chapter three, the method currently used to stabilize whole blood was modified. The stability of different concentrations of a first stabilizing agent (Chromium Chloride hexahydrate) was investigated. Incubation periods and concentrations of paraformaldehyde as second stabilizing agent were investigated. Blood samples from healthy individuals (n=10) were stabilized and monitored for the routine HIV phenotypic surface antigens over a period of 40 days. These samples (n=10) were compared on the Becton Dickinson Biosciences (BD) FACSCalibur™ versus BD FACSCount™ instrumentation. Blood samples (n=3) were stabilized and monitored to identify phenotypic cell surface molecules for as long as possible. They were quantified on both flow cytrometric instruments. In addition, these stabilized samples (n=3) were investigated as control blood for calibration purposes on the BD FACSCount™ instrument. In Chapter four, lymphocytes were isolated and activated with various stimuli to express sufficient activation antigens such as CD25, CD69, HLA-DR and CD40 Ligand on the T helper cell surfaces. These activated antigens were analyzed on the BD FACSCalibur™ and further stabilized to serve as possible IQA samples in future. Results: In Chapter three, the ten individual stabilized samples had non-significant P values (P > 0.05) for CD3, CD4 and CD8 percentages and absolute values comparing day 3 until day 40. Comparing the BD FACSCalibur™ versus BD FACSCount™, resulted in a R2 = 0.9848 for CD4 absolute values and a R2 = 0.9636 for CD8 absolute values. Stabilized blood samples (n=3) were monitored for routine HIV phenotypic markers until day 84. The cells populations were easily identifiable and could be quantified on both BD FACSCalibur™ and BD FACSCount™ instruments. In Chapter four; for the activation study purposes, activated T helper lymphocytes expressed approximately 25 to 35% CD40 Ligand cell surface molecules. The stimulant of choice was Ionomycin at a 4μM concentration. Cells were incubated for four hours at 37 degree Celsius in a 5% CO2 environment. For CD69 surface expression, 6 hour incubation was optimum. The stimulus of choice in this case was 4μM Ionomycin which induced 84.21% CD69 expression in the test samples. For CD25 expression; 6 hour incubation with PHA resulted in approximately 43% of CD25 expression. For HLA-DR surface expression; 6 hour incubation with PHA resulted in approximately 43.32% of HLA-DR expression. Activated lymphocytes expressing CD40 Ligand showed stability until day 23. Activated Lymphocytes expressing CD69, CD25 and HLA-DR were stabilized in the same manner and stability could be achieved until day 16. Conclusion: This thesis was related to the preparation of control samples (IQA) designed to simulate whole blood having defined properties in clinical laboratory situations. In future kits can be developed with a low, medium and high control sample for the various immunological phenotypic determinants. Another kit can be compiled where various activation markers can be identified, quantified with a “zero”, low and high control. These whole blood IQA kits and “activation IQA kits” can be implemented for training of newly qualified staff, competency testing of staff, method development, software testing, panel settings and instrument setting testing. Control samples ideally must have a number of properties in order to be effective. For instance stability during storage times, preferably lasting more than a few weeks, reproducibility and ease of handling. These will provide the information on day-to-day variation of the technique or equipment which will enhance accuracy and improve patient care.
AFRIKAANSE OPSOMMING: Inleiding: Vloeisitometrie tegnologie het verskeie tradisionele laboratorium toetse vervang as gevolg van beter akuraadheid, sensitiwiteit en vinniger beskikbaarheid van resultate in ‘n kliniese omgewing, veral kliniese proewe. Vloeisitometrie is ‘n kragtige tegniek om chemiese (fluorokroom byvoeging) en fisiese (sel grote en kompleksiteit) karakter eienskappe van individuele selle te meet. Met die toename in gebruik en gewildheid van hiedie instrumente, neem die behoefde toe vir gevorderde kwaliteit kontroles, gestandardiseerde prosedures, met profesionele toets programme tesame met metode ontwikkeling. Klein verstellings aan instrument parameters beinvloed die betroubaarheid, herhaalbaarheid en sensitiwiteit van ‘n sitometer en moet gemonitor (en dokumenteer) word om identiese kondisies van leesings op ‘n daaglikse basis te verseker. Dit kan bereik word deur in te skakel met ‘n interne kwaliteits versekerings program [IQA: “Internal Quality Control”] en/of ‘n eksterne kwaliteits versekerings program [EQA: “External Quality Control”] te volg. Op die oomblik is daar geen sulke kwaliteits versekerings programme in Suid Afrika en/of in die verarmende Afrika lande beskikbaar nie. MIV is ‘n wêreldwye bekommernis en laboratoriums en klinieke in hierdie gedeeltes van die land verlang ‘n dringende behoefdte vir sulke “IQA” programme om kwaliteit van instrumentasie en akkurate pasiënt resultate te verseker wat tot beter behandeling van pasiënte lei. Kwaliteit versekerings programme soos “CD Chex®” en “UK Nequas” is beskikbaar, maar baie probleme met verwysing na monster integriteit as gevolg van tydsame vervoer en aflewering kondisies word hiermee geassosieër. Die behoefte het ontstaan vir ‘n laboratorium in Suid Afrika wat direk die omliggende laboratoriums, hospitale en klinieke kan voorsien met gestabiliseerde blood monsters wat gebruik kan word as “IQA”. Die vervoer en aflewerings kondisies van hierdie monsters sal aansienlik verbeter as gevolg van die korter aflewerings afstand wat direk die beperkte temperatuur wisseling beinvloed. Doel van studie: Die doelwit van hoofstuk een is om vir die leser ‘n inleiding te gee tot terminologie en konsepte van immunologie en die immune sisteem. Hoofstuk twee beskyf die impak wat gestabiliseerde heelbloed het op die kliniese immunologie met betrekking tot kwaliteit beheer en kwaliteit versekering. Die doelwit van hierdie studie is om heelbloed te stabiliseer sodat die rakleeftyd meer as 30 dae is en sodoende as verwysings-materiaal kontroles vir Suid Afrikaanse immunofenotipering kan dien. Dit is ‘n verdere doelwit om hierdie tuis-gestabiliseerde kontrole monsters te gebruik as “IQA” verwysings materiaal in verarmende Afrika lande. Die doelwit van hoofstuk vier is om limfosiete te stimuleer om verskeie aktiverings merkers uit te druk op hul selmembrane en dan te stabiliseer en dié te gebruik as Kwaliteits Kontroles vir die meer gespesialiseerde immunologiese toetse. Studie ontwerp: Hoofstuk drie beskryf ‘n aangepaste en verbeterde metode van heel bloed stabiliseering. Stabiliteit word ondersoek in ‘n verskyndenheid konsentrasies van ‘n primêre stabiliseerings agent (chromium chloried heksahidraat) en inkubasie periodes met paraformaldehied as tweede stabiliseerings agent word deeglik gedokumenteer. Bloedmonsters van gesonde indiwidië (n=10) was gestabiliseer en gemonitor vir roetine MIV membraanoppervlak antigene oor ‘n periode van 40 dae. Hierdie monsters (n=10) was gelees en geanaliseer op ‘n BD FACSCalibur™ en vergelyk met ‘n BD FACSCount™ vloeisitometer instrument. Drie gestabiliseerde heelbloed monsters (n=3) was gemonitor vir ‘n periode vir so lank moontlik die fenotipiese selmembraan molekules identifiseerbaar was en die kwantiteit bepaalbaar was. Hierdie drie monsters was gemeet op beide instrumente. As ‘n addisionele doelwit, was hierdie drie gestabiliseerde monsters ondersoek om as moontlike kalibrasie materiaal (verteenwoordig ‘n normale bloedmonster) te dien vir die BD FACSCount™ instrument in die oggende voor pasiënt monsters gelees kan word. In hoofstuk vier was limfosiete geϊsoleer en geaktiveer met ‘n verskyndenheid stimulante om optimale aktiveerings-antigene uit te druk op T helper selmembrane (byvoorbeeld CD25, CD69, HLA-DR en CD40 Ligand). Hierdie geaktiveerde monsters was geanaliseer op die BD FACSCalibur™ en daarna gestabiliseer. Na stabilisasie van die geaktiveerde limfosiet monsters was dit gemonitor oor ‘n tydperk so lank moontlik data plotte leesbaar en selpopulasies identifiseerbaar was. Hierdie monsters kan dien as ‘n moontlike “IQA” toets stel vir ‘n meer gespesialiseerde immunologiese aktiveerings kontrole doeleindes. Resultate: In hoofstuk drie; tien individiële gestabiliseerde heelbloed monsters het gedui op geen-beduidende P waardes (P > 0.05) vir CD3, CD4 en CD8 persentasies en absolute waardes; gemeet vanaf DAG 3 vergelykbaar tot-en-met DAG 40. Met korrelasie statistiek en vergelyking van die BD FACSCalibur™ met die FACSCount™ instrumente, is die volgende opgemerk; R2 = 0.9848 vir die CD4 absolute waardes en ‘n R2 = 0.9636 vir die CD8 absolute waardes. Drie gestabiliseerde monsters (n=3) was gemonitor vir MIV roetine fenotipeering tot en met DAG 84. Die selpopulasies was duidelik identifiseerbaar en die kwantitatief meetbaar op albei instrumente (BD FACSCalibur™ en BD FACSCount™). Hoofstuk vier: geaktiveerde T helper lymphosiete het 25 – 35% membraan CD40 Ligand uitgedruk op hul selmembrane. Die stimulant van keuse was ionomysien teen ‘n optimale konsentrasie van 4μM. Die optimale inkubasie tydperk was vier ure by 37°C in 5% CO2 kondisie. Ses uur inkubasie in 4μM ionomysien by 37°C in ‘n 5% CO2 omgewing was optimal vir die CD69 selmembraan uitdrukking en het 84.21% opgelewer. Vir CD25 selmembraan uitdrukking was die selle vir ses ure met phietoheamagglutinin (PHA) gestimuleer by 37°C in 5% CO2 kondisie en het 43% CD25 selmembraan uitdrukking opgelewer. HLA-DR selmembraan uitdrukking: selle was vir ses ure saam met PHA by 37°C in 5% CO2 kondisie inkubeer en het 43.32% opgelewer. CD40 Ligand aktivering/gestabiliseerde limfosiete het tot en met dag 23 stabiliteit getoon. Die ligand was duidelik identifiseerbaar en kwantifiseerbaar. Geaktiveerde lymphosiete wat CD69, CD25 en HLA-DR selmembraan merkers uitdruk het na die stabiliseerings proses stabiliteit getoon tot-en-met dag 16. Gevolgtrekking: Die doel van hierdie studie was om verwysingskontroles voor te berei sodat dit vars heelbloed naboots met uitkenbare eienskappe vir kliniese situasies. ‘n Toets kontrolestel met verwysings materiaal vir drie vlakke (byvoorbeeld ‘n lae, medium en hoë kontrole) absolute selwaardes en persentasies kan voorberei word vir roetine immunologiese fenotiperings merkers (CD3/CD4/CD8/CD45). Meer gespesialiseerde kontrolestelle vir meer spesifieke doeleindes kan opgemaak word wat ‘n verskydenheid van limfosiet aktiveringsmerkers bevat met byvoorbeeld ‘n “nul”, lae en hoë verwysings kontrole daarin. Hierdie heelbloed kan dien as “aktiveerde interne kwaliteits verwysings materiaal” en kan gebruik word om nuut aangestelde laboratorium werkers en nuut gekwalifiseerde studente op te lei. Hierdie verwysings materiaal / kontroles kan aangewend word vir bevoegdheids doeleindes (byvoorbeeld vir SANAS akkreditasie doeleindes), vir metode ontwikkeling, vir sagteware toetsing, vir paneel opstelling en instrument verstellings doeleindes. Die kontroles moet ‘n verskydenheid eienskappe bevat om effektief te wees. Byvoorbeeld, stabiliteit tydens storing, gewenslik meer as ‘n paar weke, herhaalbaar en maklik handteerbaar. Hierdie kontroles sal inligting voorsien op ‘n daaglikse basis tydens wisseling van tegnieke of instrumentasie wat akuraatheid beinvloed en op die ou-end direk pasiënt versorging bevoordeel.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
Problemas Relacionados a Medicamentos (PRM) sÃo responsÃveis por causar morbidade e mortalidade em todo o mundo, e tambÃm, afetar resultados clÃnicos esperados e a qualidade de vida (QV) de pacientes. O tratamento etiolÃgico da DoenÃa de Chagas (causada pelo Trypanosoma cruzi) conta apenas com o benzonidazol (BNZ). Este medicamento pode produzir toxicidade (hipersensibilidade, aplasia medular, etc.) e tem eficÃcia parcial. O objetivo deste trabalho foi avaliar os efeitos provocados na saÃde dos pacientes emu so de BNZ, medidos a partir de Ãndices QV e PRM. Dezenove pacientes foram inluÃdos em um estudo observacional, descritivo e de seguimento que ocorreu de novembro de 2006 a outubro de 2007. Estes pacientes, apÃs prescriÃÃo de BNZ e consentimento, foram acompanhados por 6 meses por um farmacÃutico e estagiÃrios treinados. O MÃtodo DÃder foi utilizado, excetuando-se a etapa de intervenÃÃo. Os PRM foram classificados por juÃzes utilizando-se o Segundo Consenso de Granada (2002). As reaÃÃes adversas foram classificadas pelo Centro de FarmacovigilÃncia do Cearà (CEFACE). Utilizou-se o questionÃrio Short-Form Health Survey (SF-36) para avaliar a QV dos pacientes antes e apÃs o seguimento. Realizou-se anÃlise descritiva para os dados. AlÃm disso, os testes de Mcnemar e Wilcoxon foram feitas para anÃlise inerencial, considerando o nÃvel de significÃncia de p<0,05. A maioria dos pacientes era homem (58%), possuÃa escolaridade atà o ensino fundamental (57,9%) e encontrava-se na forma indeterminada da doenÃa de Chagas (74%). Cerca de 42% dos pacientes fizeram uso de dois ou trÃs medicamentos durante o tratamento com BNZ, havendo mÃdia de consumo de 1,3 medicamento por paciente, sendo os anti-hipertensivos e diurÃticos os mais usados durante o tratamento com BNZ (22%). Em relaÃÃo à adesÃo ao BNZ, 47,4% nÃo foram aderentes ao BNZ. Suspenderam o tratamento, 36,8%, a maioria devido à presenÃa de RAM (Coeficiente de CorrelaÃÃo = 0,415, p-valor bicaudal = 0,047). Somou-se um total de 148 PRM nas trÃs etapas de avaliaÃÃo. Destes 41,9% estavam relacionados à necessidade, 33,1% à efetividade e 25% à seguranÃa. Verificou-se que a quantidade de PRM estava associada ao nÃmero de medicamentos usados (Coeficientes de CorrelaÃÃo Kendall = 0,438, p-valor bicaudal = 0,018). Comprovou-se que a quantidade de PRM apÃs o tÃrmino do tratamento (60 dias) foi maior em relaÃÃo ao inÃcio (Teste de Wilcoxon: Z=-3,725, p<0,05). Cerca de 17 pacientes (10 homens e 7 mulheres) afirmaram apresentar alguma RAM, que variou desde prurido a parestesia. A maioria destas foi classificada como provÃvel e leve. Demonstrou-se que os pacientes com RAM leves tÃm um conhecimento maior em relaÃÃo Ãqueles com reaÃÃes moderadas (Coeficiente de CorrelaÃÃo = 0,523; p-valor bicaudal = 0,028). NÃo foi detectada alteraÃÃo da QVRS apÃs o seguimento. Entretanto, mostrou-se que os PRM afetaram a QVRS (Teste de Wilcoxon: Z=-3,724, p<0,05). NÃo houve diferenÃa entre QVRS antes e depois, no entanto houve piora da QVRS em relaÃÃo aos PRM.
Drug Related Problems (DRP) are responsible to cause morbidity and mortality in all world, and can affect expected clinical results and quality of life (QoL) of patient. Etiologic treatment for Chagasâ disease (caused by Trypanosoma cruzi) have only a drug, the benznidazole (BNZ). This medicine may produce toxicity (hipersensibility, bone medular aplasy, etc.) and have partial efficacy. The aim was to estimate the effects in the health of patients in use of BNZ, mensured by QoL and DRP. Nineteen patients included in a observational, descriptive and follow-up study in the period from November of 2006 to October of 2007. These patients, after prescription of BNZ and consent, were followed by 6 months by pharmacist and pharmacist students. Dader Method was utilized except intervention procediment. DRP were classified by judges utilizing the Second Granada Consensus (2002). The adverse reaction were classified by Centro de FarmacovigilÃncia do Cearà (CEFACE). The QoL was mensuread by Short-Form Health Survey (SF-36) questionnaire before and after the follow-up. Were realized by descriptive analysis to study the result. Also, Mcnemar and Wilcoxon tests were made for inferential analysis, considering the significance level p<0,05. The majority of patients were men (58%), had until primary school level (57,9%) and they were in a indeterminate form of Chagas disease (74). About 42 from patients used 2 or 3 medicines with BNZ treatment, with an average from 1,3 medicine per patient. Antihypertension and diuretics were the most utilized in BNZ treatment (22%). In relation to adherence, 47,4% from patients were not adhere to BNZ. The use of BNZ was suspended in 36,8% of patients, the major reason was adverse reaction (Correlation Coefficient = 0,415, p-value = 0,047). In three steps of analysis was founded a total of 148 DRP (41,9% related to necessity, 33,1% to effectiveness and 25% to security). DRP were associated to number of medicines (Kendall Coefficient = 0,438, p-value = 0,018). The number of DRP were high after than the start of treatment with BNZ (Wilcoxon test: Z=-3,725, p<0,05). Seventeen patients (10 men and 7 women) showed adverse reaction, to pruritus until parestesia. These majority reactions were classified as probable and soft. Patients with soft adverse reaction have more knowledge level in relation to patients with moderate adverse reaction (Correlation Coefficient = 0,523; p-value = 0,028). It wasnât detected alterations in QoL after follow-up, but it was showed that DRP affected QoL levels (Wilcoxon test: Z=-3,724, p<0,05). There wasnât difference between QoL before and after, however DRP affected QoL.

Diarrheal diseases are a global public health burden, killing 1.8 million people annually. Diarrhea disproportionately affects children and those in poverty. Most diarrheal cases can be prevented through safe drinking water, basic hygiene and/or sanitation measures, with drinking water interventions having the most impact on reducing diarrheal disease. A meta-evaluation was completed of studies evaluating a specific household water treatment method, the biosand water filter. Results from the meta-evaluation illustrate that biosand water filters improve drinking water quality and reduce diarrheal disease. However, there is no generally agreed upon field method for determining biosand water filter effectiveness that is useable in low-resource communities. A pilot study was conducted of potential field use indicators, including the Colilert coliform Presence/ Absence test, hydrogen sulfide, alkalinity, hardness, pH, and fluorescently-labeled latex microspheres. The study included both laboratory and field testing. The Colilert Presence/ Absence test had the highest correlation to the United States Environmental Protection Agency standard method (IDEXX Quantitrays), but more data is needed before making a recommendation. This study adds to understanding about evaluation of biosand water filters and provides preliminary data to address the need for a field use indicator for biosand water filters.

Australia�s policy on Quality Use of Medicines (QUM) aims to achieve appropriate use of medicines and improved health outcomes. Drug and Therapeutics Committees (DTCs) are educators, policy makers as well as financial gatekeepers in matters relating to medicine use. Increasingly, DTCs are also involved in risk management and clinical governance. As such, DTCs could be considered to be QUM advocates in the institutions in which they function. In a health care arena where there are escalating demands on high standards of clinical practice, quality assessment and improvement is essential in ensuring safe and effective patient care. Given the role DTCs play in safeguarding the interests of the stakeholders of the health care system, research into ways in which DTC performance could be enhanced is required. Although indicators specific to DTCs exist, the literature does not seem to provide straightforward answers to the question of what is currently being done in terms of quality assessment and quality improvement of DTCs. In the absence of such data, an opportunity for research is clearly identified. The first aim of this research project was to gain insight into the current activities undertaken by, and challenges facing Australian DTCs. Following this, the second aim was to explore ways in which DTC performance could be augmented. In addressing the first aim of this project, a national survey of Australian DTCs was conducted. These findings reinforce the evidence in the literature about the roles, structure and stakeholder expectations of DTCs. Our research also documents DTCs� quality improvement initiatives and barriers to DTC activities. It appears that there is little support available to Australian DTCs. Further, a case study was undertaken in order to gain an understanding of the depth and detail of DTC operations. An audit of a DTC in an Australian hospital was conducted. This study revealed that DTC decisions are being implemented in an ad hoc manner. In fact, there were no strategies (or action) planned to implement the majority of their decisions. This could have an impact on DTC performance. In view of this finding, qualitative methods were used to explore stakeholder opinions regarding the implementation of DTC decisions and policies. Stakeholders believed that strategies used to implement DTC policies should be targeted (to the audience as well as the type of decision/policy being implemented), timely, and delivered at the point of care. Face-to-face strategies were perceived to be more effective than printed materials, particularly when an influence on clinical practice was desired. Stakeholders also felt that the lack of resources was a significant barrier to DTC performance augmentation. This probably contributed to a lack of follow-up (or review) of implemented policies. According to stakeholders, other barriers to policy implementation include a lack of ownership of policies, low DTC profile, and an over-reliance on pharmacy to implement DTC decisions. Stakeholders felt one of the ways in which DTC performance could be improved was to prioritise DTC decisions for implementation. In pursuit of a method to prioritise DTC decisions, a survey was conducted. Stakeholders identified patient safety, cost, and the practice of evidence-based medicine as domains of important DTC decisions. The results also suggest that stakeholders recognise the need for the prioritisation of DTC decisions for implementation. Stakeholders implied that higher priority would be assigned to DTC decisions considered to be important. In a follow-up survey, stakeholders (including doctors, nurses, pharmacists, and DTC members) seemed to have agreement of the primary domains of DTC decisions. Higher levels of importance and higher priority were assigned to decisions involving the primary domains of patient safety and cost. However, level of importance and priority assignment were not consistently correlated. The work presented in this thesis suggests that there are ways to improve DTC performance. Although conducted primarily on hospital-based DTCs, it is anticipated that the lessons learnt could be applied to state-based, or even, Area Health-based DTCs. In conclusion, this research found that there was a range of views regarding �importance� and prioritisation for implementation. Social, organisational, as well as environmental factors may contribute to this. Future research should examine other possible factors contributing to the importance and priority of DTC decisions, so that DTC policy could be appropriately implemented into practice.

This study expands the current knowledge base on the nature, causes and fate of unused medicines in primary care. Three methodologies were used and participants for each element were sampled from the population of Eastern Birmingham PCT. A detailed assessment was made of medicines returned to pharmacies and GP surgeries for destruction and a postal questionnaire covering medicines use and disposal was used to patients randomly selected from the electoral roll. The content of this questionnaire was informed by qualitative data from a group interview on the subject. By use of these three methods it was possible to triangulate the data, providing a comprehensive assessment of unused medicines. Unused medicines were found to be ubiquitous in primary care and cardiovascular, diabetic and respiratory medicines are unused in substantial quantities, accounting for a considerable proportion of the total financial value of all unused medicines. Additionally, analgesic and psychoactive medicines were highlighted as being unused in sufficient quantities for concern. Anti-infective medicines also appear to be present and unused in a substantial proportion of patients’ homes. Changes to prescribed therapy and non-compliance were identified as important factors leading to the generation of unused medicines. However, a wide array of other elements influence the quantities and types of medicines that are unused including the concordancy of GP consultations and medication reviews and patient factors such as age, sex or ethnicity. Medicines were appropriately discarded by 1 in 3 patients through return to a medical or pharmaceutical establishment. Inappropriate disposal was by placing in household refuse or through grey and black water with the possibility of hoarding or diversion also being identified.

[Truncated abstract] Background: This thesis examines pharmacotherapy use in the secondary prevention of coronary heart disease. It includes antiplatelet agents, beta-blockers, statins and ACE inhibitors, all shown in landmark clinical trials and meta-analyses to reduce the risk of cardiac events in patients with known coronary disease. Underuse of effective preventive therapies represents a lost opportunity to reduce mortality and morbidity. Overseas studies have shown significant underuse of effective therapies at the time of hospital discharge following an acute event and later in ambulatory care. Australian data on prescribing practices following an acute coronary event and, ongoing use in ambulatory care are sparse. Aims: The aim of this thesis was to quantify the prescription of known effective therapies at the time of hospital discharge following an acute coronary event and ongoing use in ambulatory care. A secondary aim was to identify barriers to optimal secondary prevention thus providing an evidential basis to recommend change. Methods: This was an observational study of a cohort of post-MI patients admitted to a tertiary and affiliate hospital in Perth, Western Australia. The continuum of care from the treatment plan at discharge through to the treatment regimen and risk factor management 12 months post-MI was examined. The intermediate step, communication about the treatment plan with the patient and the primary health care provider was also examined. The study involved a review of hospital medical records and follow-up questionnaires to patients and their general practitioners at 3 and 12 months post-MI. All post-myocardial patients were included in the analysis of prescriptions at discharge. The follow-up study included patients 80 years and younger with no terminal conditions. Patient interviews at 3 months and interviews and focus groups with key hospital staff provided qualitative data to inform the quantitative data.

Adherence to medication is a major issue in chronic illnesses in general and is of particular concern in children, who are often dependent on their parents/carers for medication administration. Adherence to the immunosuppressant mycophenolate in children with kidney transplant, which is poorly studied worldwide, was evaluated in the present research using a range of different measures for adherence assessment and triangulating the results. These methods were: measuring mycophenolic acid (MPA) concentration in plasma and dried blood spot (DBS) samples, patient self-report questionnaires, and pharmacy and prescriber records. MPA is the active form of mycophenolate in vivo. Factors which could influence patient adherence were explored via administration of questionnaires to patients and their carers including: the Beliefs about Medicines Questionnaire (BMQ), the Centre of Epidemiologic Studies Depression (CES-D) Scale, Paediatric Quality of Life Inventory (PedsQL™ Transplant Module) and consideration of demographical/medical information collected for each participating patient. Assay methods for the quantification of MPA in both DBS and plasma samples collected at outpatient clinics were developed using high performance liquid chromatography (HPLC) and validated according to international guidelines. Gradient elution HPLC with UV detection was utilised with the mobile phase consisting of a combination of phosphate buffer and acetonitrile; a C18 column acted as the stationary phase. A total of 33 children (8 to 18 years old) and their parents/guardians participated in the clinical study that followed. Adherence was assessed by applying the new assay methodology to determining MPA concentrations in paediatric samples and comparing these with predicted concentrations based on child parameters (weight, medication dose, co-medications) using population pharmacokinetic (PopPK) modelling simulations. This novel approach was found to be a useful in the assessment of patient adherence when combined with the other measures detailed above. Overall non-adherence to mycophenolate in the children with kidney transplant who participated in the research (n=33) was found to be 36.4%. Logistic regression analysis indicated that children who suffer from medication side effects were statistically more likely to be non-adherent. Although the adherence work formed the main body of the research presented in the thesis, two supplementary, supporting research projects were also included (i) A review of questions and answers raised in a patient online discussion forum for use by patients with kidney transplant and (ii) an online survey of paediatric clinical pharmacists on prioritising future research needs in the area of medicine use in children. In the discussion forum it was established that the concerns experienced by patients with kidney transplant could be categorised into three themes: concerns related to the clinical manifestations, concerns related to transplant management, and concerns about the transplant impact on daily life. Although the majority of users of the forum were adults, such concerns are expected to affect children with kidney transplant as they reach adulthood and could form a framework for the development of early interventions. The online survey of practicing paediatric pharmacists indicated that high priority should be given to new research in the areas of medication administration, pharmacokinetics, the use of extemporaneous formulations, pharmacovigilance of medicines, the use of ‘Specials’ and the use of off-label or unlicensed medicines in children. It is hoped that, when published, the priority list developed will act as a guide for prioritising new research projects on medicine use in children nationally and internationally.

O envelhecimento populacional está correlacionado com o aumento dos custos e dos cuidados em saúde, e pela piora na qualidade de vida. O objetivo deste estudo é conhecer o perfil de consumo de medicamentos e o índice de qualidade de vida de grupos de pacientes idosos usuários do SUS e de planos de saúde privado e descrever o custo mensal do tratamento. A pesquisa seguiu um modelo de estudo transversal, e utilizou como instrumento de coleta de dados dois questionários estruturados, com amostragem foi do tipo intencional. O projeto foi aprovado pelo CEP/UFRGS. A coleta de dados foi realizada no período de março a julho de 2007, com 225 idosos, sendo: 61 na classe A, 80 na classe C e de 84 na classe E. A maioria era do sexo feminino, com idade média de 70 anos. O número médio de medicamentos citados foi: na classe A= 5,34; C= 4,07; E= 4,28. O custo de referência dos medicamentos variou entre as classes sociais estudadas, sendo: na classe A, de R$ 226,55 (DP±161,92), na classe C de R$ 72,32 (DP±82,86). O custo social dos medicamentos foi: na classe A de 210,03(DP±152,52); na classe C de 86,10 (DP±80,09) e para classe E de 78,39 (DP±167,92). Estatisticamente observou-se que a classe A diferiu da demais em relação ao custo dos medicamentos. Na classificação dos medicamentos de acordo com o valor intrínseco foi observado que na classe A 39% dos medicamentos apresentaram valor elevado, esse valor elevou-se para 52% e 59% classe social C e E, respectivamente. Quanto aos escores obtidos no questionário SF-36 para qualidade de vida o valor máximo na classe A foi de 89,45, relacionado ao aspecto social, na classe C os maiores escores foi no item relacionado ao estado geral de saúde e o aspecto emocional apresentou os maiores valores na classe E. Houve diferença estatística entre classe A e as classes C e E nos domínios dor, vitalidade, aspecto social e saúde mental. Este estudo possibilita o desenvolvimento de novas hipóteses de investigação para a construção de ações voltadas para a garantia de acesso dos idosos aos serviços de saúde, não só em quantidade, mas em qualidade, que contribuam para a qualidade de vida e segurança na utilização de medicamentos.
The population aging is correlated with the increase of the costs and the health´s care, and with the worsening in the life quality. The objective of this study is to know the profile of medicine consumption, the index of life quality of elder groups which use the SUS and the private health plans and to describe the monthly cost of the medicines treatment. The research followed a model of transversal study and used as instrument of data collection data two structuralized questionnaires with intentional type of sampling. The project was approved by the CEP/UFRGS. The data collection was carried out in the period of March to July of 2007, with 225 elder people, being: 61 in the class A, 80 in class C and 84 in class E. The majority was female with a mean age of 70 years old. The mean number of medicine used was: in class A=5,34; C = 4,07; E = 4,28. The medicines cost of reference varied between the studied social class being: in class A, of R$ 226,55 (DP±161,92), in class C of R$ 72,32 (DP±82,86). The social cost of medicines was: in class A of 210,03(DP±152,52); in class C of 86,10 (DP±80,09) and for class E of 78,39 (DP±167,92). It was observed that the class A differed of the other classes in relation to the cost of medicines. In the medicines classification, in accordance with the intrinsic value, it was observed that in class A 39% of medicines have presented a high value, which is 52% and 59% to the social classes C and E, respectively. In relation to the questionnaire SF-36 for life quality, the maximum value in class A was 89,45, related to the social aspect, in class C the greater value was related to the general state of health and the emotional aspect presented the biggest values in class E. There were difference statistics among classes A, C and E in the pain, vitality, social aspect and mental health. This study makes possible the development of new hypotheses of inquiry for the construction of actions directed to guarantee the access of elder people to the health services, not only in amount, but in quality, that contribute for the quality of life and security in the medicine use.

Polysaccharides are abundant in Chinese medicines (CMs) and play important roles in these materials' bioactivities. But at present, the polysaccharides are seldom incorporated into the quality assessment system of CMs. One of the big bottlenecks encountered is the difficulties in quality analysis due to their large molecular mass, diverse and complex chemical structure. Hereby, in current study, evidence and improved analysis approaches related to polysaccharides quality are proposed by employing several CMs as objectives. Firstly, Lingzhi (Ganoderma lucidum and G. sinense) was used to provide evidence of the importance of polysaccharides quality assessment in CMs. The results showed that the polysaccharides from two species shared the same structural features in terms of mono-/oligo-saccharide profiles, molecular size, sugar linkages, and IR/NMR spectra. And these polysaccharides showed no obvious difference in antitumor/immunomodulating activities and mechanism related to the activation of some proteins via TLR-4 related signaling pathway and gut-microbiota modulatory effects. Following that, to solve the problems existed in qualitative and quantitative analysis of polysaccharide in CMs, a fluorescence-labeled oligosaccharide-marker approach was raised accordingly based on LC-DAD-qTOF -MS analysis. Taking Danggui Buxue Tang (DBT) as an example, the result showed that 1) selected oligosaccharide marker generated by mild hydrolyzation and ABEE-labeling could powerfully differentiate individual herb polysaccharides. 2) good linearity was established between the identified oligosaccharide-markers and individual polysaccharides (r≥0.99). 3) the established method had satisfactory repeatability (RSD≤8.4%), recovery (≥80%) and sensitivity in polysaccharide quantitation in DBT. Finally, a polysaccharide quality analysis was conducted to dynamically trace the absorption, dynamic distribution and degradation of orally-dosed DOP (a marker polysaccharide from Dendrobium officinale) in mice and in vitro using near-infrared fluorescence imaging and chromatographic analysis. The results indicate that DOP was not absorbed and digested but were quickly degraded to short-chain fatty acids in the large intestine where gut microbiota existed. The interaction could be associated with DOP's suppression of 4T1 tumor growth in mice. In conclusion, by these studies, the importance of bioactive polysaccharides in quality assessment of CMs was confirmed. The mentioned predicaments in quality analysis of polysaccharides were greatly improved whether in CMs or complex biological matrix in vivo and in vitro. All the approaches proposed will contribute to other polysaccharides or polysaccharide-dominated CMs' analysis.

The production and distribution of counterfeit drugs is a critical health problem that plagues nations worldwide. The presence of counterfeit antimalarials has become especially worrying, as these drugs are most often needed by those living in nations whose resources to verify the medicine supply are lacking. Rapid analysis methods used for screening large quantities of poor quality antimalarials are critical in the battle to protect those in less developed regions of the world. Simple, cost effective analysis methods that can be used in the field must be developed so those whose governments cannot afford to maintain medicine regulatory agencies can still have faith in their medicinal supply. A very powerful screening method, Direct Analysis in Real Time Mass Spectrometry (DART-MS) has been used to investigate thousands of poor quality medicines. This method, however, is known to fragment molecules more readily than commonly used, 'softer' ionization methods, such as electrospray ionization. Excess fragmentation in 'harder' ionization sources is due to deposition of additional internal energy to the ionized molecules. This internal energy deposition can be measured, so the analyst can be knowledgeable as to what to expect when examining unknowns using this recently developed ionization source. Quantitation of the active pharmaceutical ingredient (API) in pharmaceuticals is crucial to the determination of what class a poor quality medicine fits into. Because poor quality drugs can be of different types, it is important to accurately classify them, in hopes of improving the supply of medicines available to those in less developed regions of the world. High performance liquid chromatography (HPLC) is most commonly used to quantify the active pharmaceutical ingredient in poor quality medicines, however, this method is time consuming, preventing its use in high throughput settings. During the course of my research, hundreds of poor quality pharmaceuticals were analyzed using DART-MS. The active pharmaceutical ingredient was detected during the rapid screening for many of these drugs, however, a more in depth analysis would often reveal less than the expected quantity of active ingredient. A rapid non-chromatographic quantitation method was developed using a mass spectrometer as the detector. This method allows for both quantitative and qualitative information regarding a specific sample to be obtained simultaneously, saving the analyst time and resources. Utilizing this non- chromatographic mass spectrometric method, degradation products have been identified, thus increasing our ability to classify drugs into their respective divisions.

Saccharides are the main constituents of many Chinese medicinal materials, they include monosaccharides, oligosaccharides and polysaccharides. They have been proved to have many bioactivities such as immunomodulating effects, anti-cancer effects, anti-viral activities, and anti-fatigue effects. Thereby, it is necessary to establish comprehensive qualitative and quantitative analysis of saccharides. On the other hand, saccharides are the main constituent of water extract of many Chinese medicines, which contains a large amount. Up to now, only two botanical drugs, namely Fulyzaq and Veregen, have been approved by the FDA. Despite their complex chemical profiles, 85%-95% of their chemical components could be determined, enabling effective quality control. Therefore, a higher level of qualitative and quantitative analysis is expected for saccharide-rich Chinese medicines. However, currently available methods are weak in terms of accuracy and specificity. Our study aims to develop a comprehensive qualitative and quantitative analysis of saccharides in saccharide-rich Chinese medicines. In this study, a HPLC-NH2P-ELSD quantification method is developed to determine monosaccharides and oligosaccharides. A high performance gel permeation chromatography method was developed to analyze the apparent molecular weight distribution patterns and a 3-Methyl-1-phenyl-2-pyrazoline-5-one derivatization method was used for monosaccharide composition analysis of polysaccharides. The methods were well validated and were then successfully applied in quality assessment of one Chinese medicine material and three Chinese patent drugs from different manufacturers.

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária
A prótese dentária destina-se à substituição das peças dentárias perdidas, com o restabelecimento da função oral e atendendo às suas características e finalidade, são classificadas como dispositivos médicos (DM). A sua elaboração envolve uma interacção entre o profissional de saúde, assistentes e técnicos do laboratório de prótese. Esta revisão narrativa teve como propósito catalogar e definir os DM em Medicina Dentária, em particular os dispositivos médicos feitos por medida (DMFM, próteses dentárias); Pretendeu-se ainda enumerar as principais vias de transmissão de infecções e os conceitos gerais acerca da biossegurança que orientam o controlo de infecção relativamente aos ambientes clínico e laboratorial, nas reabilitações com DMFM; rever orientações da literatura quanto à comunicação entre o laboratório de prótese e a clínica de Medicina Dentária, particularmente quanto às possibilidades de rastreabilidade dos DMFM, em termos de controlo e biossegurança, e seus contributos para a prática clínica. A pesquisa foi efectivada aplicando a seguinte terminologia: “medical device”, “classification”, “CE mark”, “custom-made”, “dental prostheses”, “instructions for use”, “single-use”, “reprocessing”, “cross infection”, “dental office”, “prosthodontic”, “infection control”, “disinfection”, “sterilization”, “traceability”, “communication”, “written instructions”, “quality”, “dental laboratory”, “identification”, “unique device identification”, “denture marking” e “bar code” e teve por base estudos de revisão sistemática, revisão, observacionais transversais, orientações e decretos-lei. A biossegurança é um conceito que reflecte as medidas preventivas que deverão ser adoptadas visando o controlo dos riscos existentes na confecção de um DMFM, sendo que implica uma coordenação entre equipas (Médico Dentista/Pessoal Auxiliar/laboratório) de modo a garantir o cumprimento de medidas que evitem a transmissão de microrganismos; A rastreabilidade consiste no conhecimento do ciclo de vida de um produto, sendo que os registos escritos das distintas acções e tecnologias que permitam a identificação destes dispositivos contribuem para este facto. A segurança do paciente e de todos os profissionais que estão envolvidos no processo de fabrico das próteses dentárias deve ser uma prioridade, sendo que o cumprimento dos critérios de documentação facilita a rastreabilidade e o controlo de qualidade e segurança do DMFM. Dental prosthesis is intended for replacement of lost dental pieces restoring the oral function and, taking into account their characteristics and purpose, are classified as Medical Devices (MD). Its preparation involves an interaction between the dental professionals, dental assistants and dental lab technicians. This narrative review aimed to catalog and define the MD in dentistry, in particular custom-made medical devices (CMMD, dentures); It was still intended to enumerate the main routes of infection transmission and general concepts about bio-safety that guide infection control in relation to clinical and laboratory environments during rehabilitation with CMMD; to review literature guidelines concerning communication between laboratory and dental clinics, particularly as to the possibilities of CMMD traceability in terms of control and bio-safety, and their contributions to clinical practice. The research used the following terminology: "medical device", "classification", "CE mark", "custom-made", "dental prostheses", "instructions for use", "single-use", "reprocessing" "cross infection", "dental office", "prosthodontic," "infection control", "disinfection", "sterilization", "traceability", "communication", "written instructions", "quality", "dental laboratory", "identification", "unique device identification", "denture marking" and "bar code" and methodology included, systematic and narrative reviews, cross-sectional observational studies, guidelines and law directives. Biosafety is a concept that reflects the preventive measures to be taken, concerning the auditing of existing risks, regarding elaboration of CMMD, and that implies coordination between teams (Dentist/dental Assistants / Lab technicians’) to ensure compliance with measures to prevent microorganisms transmissions; Traceability is the knowledge of the life cycle of a product, and the written records of different actions and technologies that enable the identification of these devices contribute to this. Patient safety and all professionals who are involved in the manufacture of dental prostheses process should be a priority, and the fulfillment of the documentation facilitates CMMD traceability, safety and quality controls.

The aim of this thesis was to develop and evaluate methodologies to assess the impact of medicines use review (MUR), a new service introduced under the new Community Pharmacy Contract in April 2005. A cohort study utilised a prospective active group of 120 patients recruited from 7 pharmacies across Kent with a retrospective control cohort matched for age, sex, GP practice and number of medicines. The primary outcome measure was a reduction in drug therapy problems (DTPs) with a 64% resolution observed in the active group compared to only 3% in the control group over the six month period of the study. The effect size was significant (p<0.0001) with an absolute risk reduction of 61% and a number needed to treat of 1.6. This means for every 16 DTPs receiving an intervention, 10 DTPs would be resolved over and above standard care at 6 months. There were no significant differences in secondary outcome measures (number of repeat medicines and use of health services) between the two groups. A focus group of 6 patients not involved in the main study confirmed that MUR was well received by patients with overarching themes of awareness and trust. In addition a semi-structured questionnaire completed by 72 study participants confirmed that MUR was well received by patients. Two further focus groups of 6 pharmacists (providers and non-providers of MUR) were also conducted which raised contrasting views regarding the New Pharmacy Contract but showed an overwhelming consensus between both groups that MUR was a beneficial service. On the basis of these results, one can conclude that the hypothesis 'MUR will reduce drug therapy problems and will be well accepted by both patients and pharmacists' can be accepted. These findings make an original contribution to the literature and represent a significant contribution to the evidence base in support of MUR services.

Magister Pharmaceuticae - MPharm
Access to quality healthcare in South Africa is known to be unequal, with those who can afford it, receiving the best quality healthcare services in the private sector, and those who cannot afford it, having to receive healthcare in the public sector. The South African government is implementing the National Health Insurance to remove unequal access to healthcare services. However, the aim of this study is to evaluate the current usage of medicine.

Background, aim and objectives: Evaluating quality of care is essential when redesigning or improving practice. Medicines reconciliation (MR) on hospital admission is now policy in the UK. It is the process of obtaining an up-to-date and accurate medication list and documenting any discrepancies. The overall aim of this work was to develop quality indicators to evaluate MR on admission to hospital; the specific objectives include developing MR quality indicators, achieving consensus on their appropriateness and testing their feasibility by applying them in a hospital setting. Design: The study was designed in three parts, each consisting of three steps. In part I, ideas about potential indicators were obtained from two sources: a literature search and the nominal group technique. These ideas were converted to potential indicators using criteria for good indicators and then reviewed by nine reviewers. Part II was designed to achieve consensus on the appropriateness of the indicators to evaluate MR. It involved pre-piloting, piloting and conducting the main two-round online Delphi study. Several methods were used to approach predefined experts. Part III involved applying in hospital settings those MR indicators that had achieved consensus. It included developing operational definitions and directly observing the MR process as conducted by pharmacy staff in two hospitals. The indicators were further tested by collecting data about the MR process for all patients seen by pharmacy staff on one weekday in the two hospitals. Results: A systematic approach was followed to develop MR indicators. The idea generation step produced over 90 ideas about potential indicators, which were converted to 85 MR indicators. The assessment by the nine practicing hospital pharmacists discarded 29 of them and the remaining 56 MR indicators were carried forward to the Delphi study, during which 41 indicators achieved consensus as appropriate for evaluating MR on admission to hospital. In the feasibility study, 5 MR indicators were found not to be feasible and three not adequately assessed, while 33 indicators were considered feasible to be used in a hospital setting. Conclusions: This work provided a novel list of 33 indicators that achieved consensus and were found to be feasible to evaluate the MR process on admission to hospital. Further research should explore the use of these indicators, among others, to assess and improve the overall quality of care provided to patients on admission and throughout the hospitalization journey.

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.

While access to essential medicines has become recognised as a human right, problems concerning the inappropriate use of medicines have emerged. Medicines lose their therapeutic value and can impair both individual health and public health if inappropriately used. Inappropriate use of medicines diminishes the quality of healthcare and causes resources to be wasted, which is especially serious in under-resourced countries. To improve the use of medicines, the introduction of standard treatment guidelines (STGs) is suggested as a potential strategy. The aim of this DrPH thesis is to study the use of medicines, focusing on adherence to new STGs in Community Health Centers (CHCs) in Timor-Leste. The country is now trying to establish an equitable and sustainable healthcare system under extremely resource-limited conditions. The study used mixed research methods, collecting data from randomly selected 20 rural CHCs, 1,799 retrospective samples from patient registration books, 583 prospective observations, and 55 semi-structured interviews of health personnel were collected. Timor-Leste's medicine use was found, in general, to be acceptable. For example, use of injections was extremely low. Training, especially clinical nurse training, influenced knowledge of, attitudes to, and practical use of medicines and also prescribing adherence to STGs. Other factors that influenced the use of STGs were: health personnel's agreement with the policy concept and contents of STGs; health personnel's positive perception of the changes brought about by the introduction of STGs; development of STGs in a health policy framework: the fact that their STGs were easy to use repeatedly; and a supportive environment and systems to use STGs. Constant socialisation and timely updates of STGs are necessary. Interrelation and consistency across policies and programs should be maintained. The position of training within the health policy framework should be clearly understood by the all people concerned. Follow-up supervision is needed both for individuals and the CHC. Anticipated support should be well functioning.

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Coordenacao de Aperfeicoamento de Pessoal de Nïvel Superior
This study evaluated the QL of end-stage renal patients submitted to hemodialysis and their adhesion to daily pharmacologic treatment knowing their life expectancy and the main complications presented during HD It is an epidemiologic descriptive tranversal and quantitative research carried out at a hemodialysis clinic of a university hospital of Alfenas State of Minas Gerais Brazil with the participation of all the 30 dialysis patients in the period of the collection of data A questionnaire was used for the obtainment of data about the participants' characterization adhesion to pharmacologic treatment and life expectation QL was analyzed through the instrument WHOQOL-bref of the World Health Organization The data were tabulated in the statistical program SPSS version 10.0 and analyzed by means of the medium score with application of the following tests Qui-square Coefficient of Correlation of Pearson Test of Wilcoxon Student s t test Cronbach s Alpha Coefficient The results showed that most of the interviewees referred that HD interfered in their professional activities and in leisure and recreation but 53.33% were calm during the permanence in the clinic The most frequent complications were the arterial hypotension vomit and dizziness All the patients take medicines mainly antihypertensives With regard to knowledge of the indication of the medicines 40% of the dialysis patients know all the drugs that they take Thirty patients informed to take the medicines daily but 16.66% have already interrupted the treatment on their own account due to adverse reactions The average scores of QL were General QL 3.26 physical domain 3.10 psychological domain 3.58 social relationships 4.19 and environment 3.54 Therefore the participants of the study classified their QL as being above "neither bad, nor good" while the domain social relationships was evaluated between "good" and "very good" The variables did not interfere in the patients' QL in other words they did not present any correlation with the domains of WHOQOL-bref Through the reproducibility it was verified that the interviewees' QL was stable between the "test" and the "retest" having satisfactory reliability while the internal consistency of WHOQOL-bref was acceptable for the facets and domains indicating a homogeneity in the appraised items The main expectation of the patients' life is receiving a renal transplantation 82.35% are in the waiting list and 47.06% encountered the refusal of their relatives in donating the organ It can be verified that the instrument WHOQOL-bref showed to be effective to evaluate QL of end-stage renal patients submitted to HD thus being a reliable instrument for such a measure Finally dialysis patients will have a better QL when they are informed about their disease and treatment when cared for in a solid supportive system and rehabilitation in order to make them capable to lead an active productive and self-sufficient life
Este estudo avaliou a QV dos nefropatas crônicos submetidos à hemodiálise e sua adesão ao tratamento farmacológico de uso diário conhecer a expectativa de vida dessa população com relação ao futuro e as principais complicações apresentadas durante a HD Trata-se de uma pesquisa epidemiológica descritiva transversal e quantitativa realizada em uma clínica de hemodiálise de um hospital universitário de Alfenas-MG com todos os 30 pacientes submetidos à HD no período da coleta de dados Utilizou-se para a coleta um questionário com dados sobre a caracterização dos participantes adesão ao tratamento farmacológico e expectativa de vida e a QV foi analisada por meio do instrumento WHOQOL-bref da Organização Mundial da Saúde Os dados foram tabulados no programa estatístico SPSS versão 10.0 e analisados por meio do escore médio com aplicação dos seguintes testes Qui-quadrado Coeficiente de Correlação de Pearson Teste de Wilcoxon Teste t de Student Coeficiente Alfa de Cronbach Os resultados mostraram que a maioria dos entrevistados referiram que a HD interferiu em suas atividades profissionais e de lazer e recreação mas 53,33% se sentem tranqüilos durante a permanência na clínica As complicações de maior ocorrência foram a hipotensão arterial vômito e tontura Todos os pacientes fazem uso de medicamentos sendo os antihipertensivos os mais utilizados Quanto ao conhecimento da indicação dos medicamentos 40% dos renais crônicos conhecem todos os fármacos que usam Os 30 pacientes estudados informaram tomar os medicamentos diariamente mas 16,66% já interromperam o uso por conta própria devido a reações adversas Os escores médios referentes à QV foram QV geral 3,26 domínio físico 3,10 psicológico 3,58 relações sociais 4,19 e meio ambiente 3,54 Assim os participantes do estudo classificaram a QV como sendo acima do nem ruim nem boa enquanto o domínio relações sociais foi avaliado entre boa e muito boa As variáveis estudadas não interferiram na QV dos pacientes ou seja elas não apresentaram correlação com os domínios do WHOQOL-bref Por meio da reprodutibilidade verificou-se que a QV dos entrevistados foi estável entre o teste e o reteste tendo uma confiabilidade satisfatória enquanto a consistência interna do WHOQOL-bref foi aceitável para as facetas e domínios indicando uma homogeneidade nos itens avaliados A principal expectativa de vida dos pacientes é a realização do transplante renal sendo que 82,35% estão na lista de espera e 47,06% se depararam com a recusa dos familiares em doar o órgão Pode-se verificar que o instrumento WHOQOL-bref mostrou-se eficaz para avaliar a QV de renais crônicos submetidos à HD sendo confiável para essa medida Por fim o paciente submetido à HD terá uma melhor QV quando ele for informado acerca de sua doença e tratamento quando existir um sólido sistema de suporte e reabilitação e ser capaz de levar uma vida ativa produtiva e autosuficiente

Prescribing of drugs for children is not always in accordance with their registration specifications or they may even be unlicensed which can give rise to serious adverse events. This study has found that approximately 30% of drugs prescribed in a major teaching hospital for children did not conform to the registration specifications. It has also proposed methods to improve evidenced-based prescribing in children. In addition it has provided enhanced scientific information for the prescribing of lincomycin infusions.

Background The discharge summary is a critically important form of communication when a patient is discharged from hospital. It has been shown in numerous studies that discharge summaries often lack sufficient information, with deficiencies in completeness and accuracy, and may not be received by the GP surgery before the patient’s first postdischarge contact. Poor quality medicines-related information can result in unintentional changes to the patient’s medication after discharge. Increasingly discharge summaries are being prepared and transmitted electronically; but research into the quality of medicinesrelated information in the electronic discharge summary was scant and not UK based. Aims To list and describe the content of medicines-related information in the electronic discharge summary, and evaluate the quality of information for completeness, accuracy and timeliness. To evaluate the quality of information about medication changes in the electronic discharge summary for completeness and accuracy. Method Prospective content analysis of medicines-related information in a sample of the electronic discharge summaries generated over a two month period at a 400 bed general hospital. A stratified random sample of 10% of the electronic discharge summaries were further analysed to evaluate the quality of information about medication changes; by identifying if medication changes had occurred, and whether they were listed and the reasons for changes stated completely and accurately. Results The majority of electronic discharge summaries were prepared by junior doctors, and in a timely manner in 97% of the sample of 1306 summaries. They contained medicinesrelated information categorised as allergies, discharge medications, and medication notes. Allergies data and discharge medication lists were complete and accurate in 96% and 89% of the summaries respectively; medication notes were written in 73%, most frequently about medication changes. Medication changes occurred, between admission and discharge, in 96% of cases; new medications were started (87%) more frequently than admission medications were changed (59%). Information about these medication changes were present in 69% of summaries, and were complete and accurate in 22% and 16% respectively. Complete and accurate information about all medication changes were shown in only 13% of summaries. Conclusion Electronic discharge summaries make an important contribution to patient safety in generating legible and timely information about allergies and discharge medications; but do not completely eliminate the risk of inaccurate or incomplete information. Documentation of information about medication changes in the electronic discharge summary was frequently incomplete or inaccurate. There was a gap between the need for, and provision of, information about medication changes in the discharge summary.

Variable drug response and lack of information on drug disposition and action in rare diseases are challenges that need to be addressed for safe and effective provision of medicines. The main aim of work presented in this thesis was to address these challenges in selected areas of liver disease in children. Population pharmacokinetic and pharmacogenetic analyses in children with liver transplant revealed that tacrolimus apparent clearance decreased over time, and was higher in carriers of the CYP3A5*1 allele in both donors and recipients, however, the recipient genotype showed a more profound impact. A sub-analysis in CYP3A5 non-expresser recipients, revealed that tacrolimus clearance in this subpopulation was higher in carriers of the POR*28 allele. When compared to liver transplant patients, children with intestinal transplant exhibited higher tacrolimus clearance. Several genetic variations were investigated for correlation with phannacodynamic outcomes; of these, the IL-4 -590 C allele showed a trend towards association with acute rejection in intestinal transplant patients, while selected ABCB1 SNPs at 6 months post-transplant were associated with tacrolimus associated nephrotoxicity only in liver transplant patients. Data on the use of nitisinone for treatment of tyrosinemia type I in children, revealed that, compared to dietary treatment alone, the use of this agent is associated with enhanced patient survival and decreased need for transplant, especially if the therapy is initiated early after birth. A distinct α-fetoprotein profile was noted in children who developed hepatic cancers. The population pharmacokinetics of nitisinone was evaluated for the first time in the UK population and a gradual time dependent decrease in nitisinone clearance was observed over a period of five years. A secondary aim of the present thesis was to analyse the content, quality and trends of reporting of issues relating to liver/intestinal transplantation in UK and USA newspapers. The newspaper coverage of this topic was generally poor in quantity and in quality. The general slant regarding transplantation and donation was positive, but few articles provided information regarding the means through which an individual could become a donor. In general the current research demonstrated the usefulness of population approaches in analysing the pharmacokinetics of drugs prescribed to children and the role of genetics in variable pharmacokinetic and pharmacodynamic outcomes of narrow therapeutic index drugs such as tacrolimus.

The Medicines Use Review (MUR) service was introduced in the UK in 2005 to improve patients' knowledge and use of medicines. The service, in essence, engages the patient and the pharmacist in a structured, private conversation about the patient's medicines. Pharmacies are permitted to deliver a limited number of annual MURs yet for a number of years service provision remained low. During the period of this investigation, the service attracted substantial controversy. In 2008 the UK Government called for improvements to be made to the 'quality' of service provision, with measurement of tangible patient outcomes a key concern. This thesis set out to investigate the potential value of the MUR service. First, using discourse analysis, this thesis considered the social construction of the MUR through written marketing material and its potential impact on uptake of the service, making suggestions for future situations. Next, based on a retrospective cross-sectional audit of MUR records, a practical tool for selecting patients who might benefit from an MUR consultation was developed and explained. Auditing MUR records was suggested by others as one way of tackling questions around service 'quality'. However, the cross-sectional audit suggested that such records were inadequate for assessing service quality and it is argued that quality measures should be based on the achievement of intended service outcomes. Finally, and relating to patient outcomes, this thesis includes a qualitative investigation of patients' MUR experiences, particularly patient satisfaction, as a measure of quality. In the absence of existing patient satisfaction questionnaires measuring the true dynamics of the MUR interaction, a novel conceptual framework for measuring patient satisfaction with this service was developed and is put forward. The results contained herein can contribute to the development of an intervention for measuring the benefits of the MUR versus usual care in terms of patient outcomes.

Masters of Science
Problem and significance: Off-label use of medicines is not illegal; however, it can be risky and harmful, or beneficial and innovative. The main problem of this practice is the lack of systems for monitoring adverse drug reactions, since the drugs are used in a manner that is not approved by regulatory agencies. For this reason public health protection is not guaranteed. Purpose: To identify the various systems employed in different regions to monitor/manage the risks and benefits of off-label use; and to ascertain their extent of implementation. Method/search strategy: Electronic and manual literature search was done. Articles referring to off-label medicine use were reviewed. The literature included journal articles, national MRA guidelines, international guidelines, etc. The articles were sourced from databases such as Pubmed and Google Scholar. Data was collected from both developed and emerging markets. There was no limit to publication date. Findings: Pharmacovigilance systems for off-label use do exist although the degree of commitment and advancement differs per country. Explicit off-label laws are present in the developed countries but not in the developing ones. Implications of findings: Stakeholder involvement is very important in monitoring off-label use. Reporting of ADRs can be improved by asserting the role of off-label PV in drug repositioning. The regulator is under pressure to maintain public trust through efficient control of off-label use.

Philosophiae Doctor - PhD
Studies on rational medicine use (RMU) have mainly focused on identifying, quantifying, and addressing irrational use without exploring reasons behind this irrational use. In addition, minimal work has been conducted on irrational use of medicines in the context of the growing burden of non-communicable diseases (NCDs). This PhD research examined medicine use in Eswatini, (previously Swaziland) between April 2017 and March 2019, with a focus on prescribing practices linked to specific diagnoses. It further explored factors influencing RMU, which included testing the effects of a short intervention - prescription audit and feedback coupled with small group education - on prescribing practices in health facilities.

The overall aim is to appraise and extend the evidence base on poor quality medicines found in online medicine quality surveys. The thesis starts with two systematic reviews critically appraising the existing evidence, finding a range of evidence gaps subsequently addressed in the following chapters. These include: (a) inconsistent and poor quality reporting, (b) the methods employed are subject to high degrees of risk of bias, (c) discrepancies exist in scientific evidence, and (d) a range of critical therapeutic areas require investigation of the incidence of poor quality medicines. The Delphi consensus study of Chapter 5 constructs the first reporting guidelines to standardise reporting, allowing for evidence-based conclusions. Chapter 6 finds four out of nine investigated withdrawn medicines still available for purchase in a range of countries worldwide (clobenzorex, fenfluramine, rimonabant, and sibutramine), which are subsequently acquired and chemically analysed in Chapter 7. The results from Chapter 8 find a mean of 7.7% poor quality medicines, which corroborates with the findings of the systematic review of Chapter 4, finding a mean of 10% (IQR 0-20%) poor quality medicines in online medicine quality surveys. Purchased medicines displayed a range of quality defects, including orders lacking patient information leaflets, failing pharmacopoeia bioavailability testing, the absence of various types of packaging, the non-delivery of paid orders, and failure of pharmacopoeia friability testing.

This study explored breastfeeding women and community pharmacists’ perspectives on herbal medicine use in breastfeeding. Stage 1 investigated prevalence and pattern of use of herbal medicines amongst breastfeeding women using a population-based survey. Stage 2 explored breastfeeding women’s experience of the use of herbal galactagogues and their perspectives on pharmacists’ roles. Stage 3 explored community pharmacists’ perspectives of their role in promoting safe and effective use of these medicines and supporting breastfeeding in the community.