BACKGROUND: Trachoma is a leading cause of avoidable blindness. Currently, trachoma is endemic in 57 countries, infects approximately 84 million people globally, and continues to threaten over 10 % of the world’s population with the risk of blindness. Caused by the bacteria Chlamydia trachomatis, blindness due to trachoma is caused by repeated eye infection resulting in the inflammation of the upper eyelid eventually leading the upper lid to pull inward scratching and tearing the cornea causing it to become opaque resulting in loss of vision. The World Health Organization recommends eliminating trachoma as a public health problem using the SAFE strategy: Surgery, Antibiotic, Face washing and Environmental control. OBJECTIVES: This review examined the benefits of the added value of water, sanitation, and hygiene education interventions on preventive mass drug administration for trachoma. METHODS: Trials were identified from MEDLINE, PubMed, and LISTA EBSCO databases using a series of search terms. No restrictions were put on study date, location, design, or language of publication. The abstracts were examined from each of the searches, and any abstract describing risk factors, survey results of mass drug administration (MDA), or providing a general overview of trachoma were automatically discarded. Full text of papers including the combined use of key words including SAFE, WASH, intervention, impact, added value, MDA, azithromycin/ Zithromax® were obtained for review. Twelve full texts articles were retrieved all relevant information were placed in a standardized data extraction form. MAIN RESULTS: Three studies met the complete criteria for inclusion. All studies found a significant change in reduction of active trachoma prevalence. One study focused on the added benefit of antibiotic and environmental components on hygiene education delivered by radio. Another trial compared two villages; the control community performed MDA and the surgery while the intervention village added the F and E components. The final study as well focused the added benefit of ‘F’ and ‘E’ on ‘A’. Two of the three studies found this reduction was from the added benefit of face washing ‘F’ and environmental control ‘E’ to antibiotic use. CONCLUSIONS: In order to eliminate blinding trachoma as a public health problem, recurrence of the active form of the disease must be interrupted before repeated scarring leads to trichiasis. The antibiotic component of the SAFE strategy is a quick fix to the immediate problem. The ‘F’ and ‘E’ components are the more sustainable interventions, yet little research has been done on the actual amount of added value the individual ‘A’‘F’&’E’ components have to one another. After thorough review of the articles, articles were found which documented the ‘F’ and ‘E’ components provide significant value to the overall decrease of prevalence of active. However, the limited results of the search suggest more research can better elucidate the ability of the ‘F’ and ‘E’ components to reduce trachoma prevalence and ultimately impact blinding.

TRADUÃÃO DE INSTRUMENTO PARA AVALIAR A NÃO ADESÃO DAS MÃES AO TRATAMENTO DE SEUS FILHOS COM DOENÃAS CRÃNICAS E IDENTIFICAÃÃO DAS POSSÃVEIS DIFICULDADES QUE AS MÃES ENFRENTAM PARA OBTER E ADMINISTRAR MEDICAMENTOS AOS SEUS FILHOS NO DOMICÃLIO Autora: PatrÃcia Quirino da Costa. Orientador: Ãlvaro Jorge Madeiro Leite. Tese de doutorado em SaÃde Coletiva. Faculdade de Medicina. Universidade Federal do CearÃ,2012 Muitas crianÃas portadoras de doenÃas crÃnicas necessitam uso continuo de medicamentos para o controle da patologia. A adesÃo ao tratamento à um ponto crucial para se conseguir esse controle e diversos fatores tem sido identificados para a nÃo adesÃo em crianÃas, dentre estes a carÃncia de formulaÃÃes adequadas à faixa etÃria. O Beliefs and Behaviour Questionnaire avalia a nÃo adesÃo ao tratamento medicamentoso em adultos com doenÃa crÃnica. Apresenta 30 itens em 3 subseÃÃes: convicÃÃes, experiÃncias e comportamentos, e permite identificar fatores relacionados à nÃo adesÃo. Na crianÃa, o medicamento à administrado quase sempre por um cuidador, em geral a mÃe. O objetivo do trabalho foi adaptar culturalmente e validar o BBQ para avaliar a nÃo adesÃo das mÃes/cuidadores ao tratamento dos seus filhos com doenÃas crÃnicas, e conhecer em profundidade as dificuldades enfrentadas no tratamento domiciliar. Etapas da adaptaÃÃo: traduÃÃo, sÃntese das traduÃÃes e adaptaÃÃo cultural, retraduÃÃo, revisÃo tÃcnica, prÃ-teste. ValidaÃÃo feita pela AnÃlise dos Componentes Principais, aplicando o instrumento a 28 cuidadores de crianÃas portadoras de doenÃa crÃnica que estavam internadas em hospital estadual de referÃncia pediÃtrica, em Fortaleza, identificados sequencialmente; seguido-se visita domiciliar 30-40 dias pÃs-alta hospitalar. Aos mesmos cuidadores (acrescidos de dois) foi aplicado um questionÃrio semiestruturado onde se investigava as dificuldades encontradas na busca e administraÃÃo dos medicamentos prescritos na alta hospitalar. Os dados descritivos obtidos foram quantificados por estatÃsticas simples. As entrevistas foram gravadas, decupadas e analisadas qualitativamente com apoio na fenomenologia. O questionÃrio final BBQ-Br possui 24 itens divididos em 3 seÃÃes como no original; apresentou alta confiabilidade, verificada atravÃs da anÃlise da consistÃncia interna, e valores de alfa Cronbach elevados para todas as subseÃÃes. Os itens foram agrupados em cada seÃÃo como no artigo referÃncia e apresentaram elevada correlaÃÃo entre si, avaliada pelo teste de esfericidade de Bartlett. Participaram do estudo descritivo 30 cuidadores (26 mÃes, 2 pais, 1 tia e 1 avÃ), com grau de escolaridade predominante âensino fundamental incompletoâ e residÃncia em Ãreas pobres da cidade. Dos 25 cuidadores que buscaram medicamentos no SUS apenas 4 receberam todos os itens prescritos e 21 (70%) adquiriram algum medicamento em farmÃcias privadas. Principais dificuldades na administraÃÃo de medicamentos: sabor desagradÃvel, necessidade de partiÃÃo e dureza de comprimidos, ausÃncia de dispositivo dosador. EstratÃgias mais utilizadas: diluiÃÃo ou dissoluÃÃo em Ãgua com aÃÃcar; forÃar a deglutir. No estudo qualitativo foram identificadas dificuldades de compreensÃo das orientaÃÃes mÃdicas e na obtenÃÃo de medicamentos incluindo: desabastecimento das unidades de saÃde; medicamentos entregues fora da embalagem primÃria, sem bula, sem dispositivos para administraÃÃo e sem orientaÃÃo para o uso adequado. A mÃe procura cumprir a prescriÃÃo mÃdica, embora nÃo compreenda bem o seu significado, mas, diante das dificuldades toma decisÃes cujo alcance nÃo conhece, por exemplo, interromper um tratamento. A informaÃÃo adequada e facilidade de administraÃÃo sÃo fatores limitantes para que esse papel possa ser bem desempenhado. O questionÃrio BBQBr à potencialmente Ãtil para a identificar o potencial de nÃo adesÃo e os fatores envolvidos, fac

abstract: Neglected tropical diseases (NTDs) comprise of diverse communicable diseases that affect mostly the developing economies of the world, the “neglected” populations. The NTDs Visceral Leishmaniasis (VL) and Soil-transmitted Helminthiasis (STH) are among the top contributors of global mortality and/or morbidity. They affect resource-limited regions (poor health-care literacy, infrastructure, etc.) and patients’ treatment behavior is irregular due to the social constraints. Through two case studies, VL in India and STH in Ghana, this work aims to: (i) identify the additional and potential hidden high-risk population and its behaviors critical for improving interventions and surveillance; (ii) develop models with those behaviors to study the role of improved control programs on diseases’ dynamics; (iii) optimize resources for treatment-related interventions. Treatment non-adherence is a less focused (so far) but crucial factor for the hindrance in WHO’s past VL elimination goals. Moreover, treatment non-adherers, hidden from surveillance, lead to high case-underreporting. Dynamical models are developed capturing the role of treatment-related human behaviors (patients’ infectivity, treatment access and non-adherence) on VL dynamics. The results suggest that the average duration of treatment adherence must be increased from currently 10 days to 17 days for a 28-day Miltefosine treatment to eliminate VL. For STH, children are considered as a high-risk group due to their hygiene behaviors leading to higher exposure to contamination. Hence, Ghana, a resource-limited country, currently implements a school-based Mass Drug Administration (sMDA) program only among children. School staff (adults), equally exposed to this high environmental contamination of STH, are largely ignored under the current MDA program. Cost-effective MDA policies were modeled and compared using alternative definitions of “high-risk population”. This work optimized and evaluated how MDA along with the treatment for high-risk adults makes a significant improvement in STH control under the same budget. The criticality of risk-structured modeling depends on the infectivity coefficient being substantially different for the two adult risk groups. This dissertation pioneers in highlighting the cruciality of treatment-related risk groups for NTD-control. It provides novel approaches to quantify relevant metrics and impact of population factors. Compliance with the principles and strategies from this study would require a change in political thinking in the neglected regions in order to achieve persistent NTD-control. / Dissertation/Thesis / Doctoral Dissertation Applied Mathematics for the Life and Social Sciences 2020

No / The involvement of two nurses to dispense and administer controlled drugs is routine practice in most clinical areas despite there being no legal or evidence-based rationale. Indeed, evidence suggests this practice enhances neither safety nor care. Registered nurses at two hospices agreed to change practice to single nurse dispensing and administration of controlled drugs (SNAD). Participants’ views on SNAD were evaluated before and after implementation. The aim of this study was to explore the views and experiences of nurses who had implemented SNAD and to identify the views and concerns of those who had not yet experienced SNAD. Method: Data was obtained through semi-structured interviews. Results: Qualitative thematic analysis of interview transcripts identified three key themes: practice to enhance patient benefit and care; practice to enhance nursing care and satisfaction; and practice to enhance organisational safety. Conclusion: The findings have implications for the understanding of influences on medicines safety in clinical practice and for hospice policy makers.

En tredjedel av alla bypass-operationer leder till att kärlimplantaten slutar fungerar inom ettårs tid. En anledning till detta är bildandet av ogynnsam vävnad som sker i form av ärrbildning efter implantationen. Ärrvävnaden orsakar nya förträngningar vilket leder till ett försämrat blodflöde. Kärlimplantatet Y-graft har genom sin design som följer Murray´s lag, en naturlig blodflödesfördelning. Designen i form av ett Y har kunnat bekräftas vara fördelaktig då geometrin vid utflödet minskar risken för ärrbildning. Vad som saknas för att Y-graft ska kunna komma ut på marknaden är ett lämpligt material. Med detta som bakgrund uppkom syftet med litteraturstudien att undersöka vilka material meddokumenterad klinisk historik som är möjliga att använda vid textil tillverkning av Y-graft. Genom en gedigen litteratursökning med hjälp av sökverktyg som U.S. Food and Drug Administration (FDA) tillsammans med andra databaser inom de medicinska och materialtekniska områdena, har en förståelse skapats kring vilka material som används i medicintekniska produkter och som är möjliga kandidater till Y-graft. Litteraturstudien resulterade i att materialen polyetentereftalat, polybutentereftalat, polybutester polytetrafluoreten, polyester-, polyeter- och polykarbonatbaserade polyuretaner samt polypropen, polyeten, alfatisk polyamid och silke finns i godkända medicintekniska produkter på den amerikanska marknaden. De presenterade materialen har på så visdokumenterad klinisk historik och är lämpliga kandidater att använda vid textil tillverkning av Y-graft. De godkända materialkandidaterna som presenteras kan även beläggas medbiologiska polymerer för förbättrad biokompatibilitet. Materialkandidaterna har godkänts i medicintekniska produkter av U.S. Food and Drug Administration (FDA). Genom godkännandet har alla de presenterade materialen dokumenterad klinisk historik och är där med lämpliga kandidater att använda vid textiltillverkning av Y-graft. / One third of all bypass surgeries causes vascular implants to stop working within a year. A reason for this is the formation of unfavorable tissue that occurs in the form of scarring after implantation. The scar tissue causes new constrictions, which leads to impaired blood flow. The vascular implant Y-graft, by design follows Murray's law and therefore has a natural blood flow distribution. The design in the form of a Y has been confirmed to be advantageous. The Y geometry at the outflow reduces the risk of scarring. What is missing for Y-graft to be able to enter the market is a suitable material. With this as a background, the purpose of the literature study was to investigate which materials with documented clinical history can be used in textile production of Y-graft. Through a thorough literature search, using search tools like the U.S. Food and Drug Administration (FDA) together with other databases in the medical and material engineering fields, an understanding has been created about which materials are used in medical technology products and which are potential candidates for Y-graft. The literature study concluded that the materials polyethylene terephthalate, polybutheneterephthalate, polybutester polytetrafluoroethylene are found in approved medical technology products in the United States. Polyester, polyether and polycarbonate based polyurethanes and polypropylene, polyethylene, alphatic polyamide and silk are also found in the United States medical market. These presented materials thus have documented clinical history and are suitable candidates for use in textile manufacturing of Y-graft. The approved material candidates presented can also be coated with biological polymers for improved biocompatibility. The material candidates have been approved in medical technology products by the U.S. Food and Drug Administration (FDA). With this approval, all the presented materials have documented clinical history and are therefore suitable candidates to use when manufacturing Y-graft.

Iontophoresis is a method to enhance and regulate the transdermal drug delivery by application of an electric field to the skin. Application of small electric current (µ A) enhances transport of both charged and neutral molecules across the skin. Reverse of this process enables extraction of analytes across the skin for noninvasive sensing and diagnosis. Hence it is planned to conduct detailed studies on Reverse Iontophoresis. An invitro model is developed to study the extraction of glucose across the skin. Effects of magnitude of electric current, time of application, pH etc. on the extraction of glucose are studied. It is observed that extraction of glucose at the cathode is higher than at the anode. Advantage of invitro model is the possibility of varying parameters to an extent which is impossible invivo. Instrumentation suitable for continuous monitoring of reverse iontophoresis invivo in human subjects is developed. It supplies the required current and acquires the potential profile of the skin during reverse iontophoresis. Potential profiles showed that skin resistance decreases with the application of current. Experimental results revealed that the application of pulsed DC tends to make the reverse iontophoresis more effective by enhancing the flow of analytes which is proved by the fact that skin resistance decreases and stabilizes faster in comparison to the one with direct current reverse iontophoresis. Present work emphasizes the importance of selecting an appropriate duty cycle and frequency for reverse iontophoresis. Duty cycle around 95% and frequency of 250 mHz are good for low frequency reverse iontophoresis. Effect of reverse iontophoresis on the skin recovery is observed by monitoring the potential profiles at the end of the process. In all the reverse iontophoresis experiments, safety of the patient is ensured by fixing a compliance voltage level. Finally, Instrumentation to measure the capacitance of biosensors is developed based on frequency domain technique with a sinusoidal input. Accuracy in capacitance measurements is ±5%. Glucose measurement is demonstrated with the developed instrument using a capacitance type biosensor. The obtained results are in good agreement with the standard UV-Visible spectroscopic measurements based on phenol-sulphuric acid assay method.

Ce mémoire s'intéresse à l'influence de la règlementation américaine sur la qualité des produits médicaux commercialisés au Canada et aux États-Unis. Au départ, notre recherche s'intéressait uniquement aux entreprises canadiennes mais étant donné la taille restreinte et la récence de ce marché, et qu'il nous fallait des entreprises qui avaient connu les changements règlementaires des trente dernières années, nous l'avons étendu aux entreprises américaines. L'objectif de recherche consiste à établir si la réglementation influence, à elle seule, la qualité des produits ou si c'est l'effet de plusieurs variables citées dans la littérature, notamment la technologie, les institutions de santé et les besoins d'utilisateurs. L'analyse contextuelle a permis de tracer, sur une période de trente années, les événements historiques importants qui auraient contribué à l'évolution de la qualité. Citons, sans ordre particulier, la modernisation de l'appareil règlementaire américain, la croissance des décès issus de mauvaises manipulations des appareils médicaux, l'arrivée des innovations technologiques dans le secteur de la santé, un mouvement consumériste naissant, la montée des programmes règlementaires orientés vers l'utilisateur. En optant pour une méthodologie d'entretien individuel, nous avons pu vérifier l'influence de ces facteurs, auprès des participants, tous des cadres exécutifs ayant plus de dix ans d'ancienneté dans l'entreprise, et contrôler la qualité des verbatims. L'analyse des entretiens a démontré que, selon les répondants, la réglementation influence la qualité, voire contribue à son amélioration notamment depuis 1990 lorsque la FDA a modernisé l'acte des dispositifs médicaux pour inclure les facteurs humains, communément appelés « l'expérience utilisateur ». D'ailleurs ce dernier est désormais un critère de qualité d'importance égale aux propriétés techniques des produits grâce au lobby des entreprises innovantes pour la plupart américaines. Incombe aux entreprises "en mode réaction" d'investir dans ce domaine pourtant très répandu dans d'autres industries au lieu de se contenter de corriger les défauts techniques des produits. Par ailleurs, il ressort de notre analyse que les entreprises médicales d'origine canadienne et de moindre taille auront plus de difficulté à se mesurer aux leaders américains non pas par manque de vision ou de stratégie orientée client, mais par manque de ressources et en l'absence de partenariat. Enfin, le défi qui cette-fois concerne toutes les entreprises est celui d'innover et de promouvoir les avancées technologiques dans un système réglementé qui, historiquement, ne les facilite pas. ______________________________________________________________________________

The Cytochrome P450 family of enzymes is responsible for the majority of Phase I metabolism, and has been identified as an important source of pharmacokinetic variation in therapeutic responses. CYP2C19 and CYP2D6, metabolising >35% of commonly prescribed medications, are two of the most important pharmacogenetic markers that have been studied with the aim of improving treatment response and reducing adverse drug reactions. The Food and Drug Administration (FDA) approved AmpliChip CYP450 Test (AmpliChip) was compared to a previously developed PCR-RFLP platform and a newly developed XLPCR+ Sequencing platform for the ability to identifying genotype and predicting phenotype for CYP2C19 and CYP2D6 respectively. The AmpliChip was found not to be genotypically comprehensive enough for evaluating CYP2C19 genotype, not robust enough for determining CYP2D6 genotype and inaccurate in predicting phenotype for both. The XLPCR+ Sequencing method identified three novel alleles and one sub-variant. Advances in online column-switching solid phase extraction generated a rapid and robust LCMS/ MS method for simultaneously quantifying the probe drugs omeprazole (CYP2C19 substrate), dextromethorphan (CYP2D6 substrate) and their metabolites. Antimodes were identified for phenotypic cut-offs which offered measured phenotype for comparison to predicted phenotype. Omeprazole metabolism by CYP2C19 correlated well with predicted phenotype in a demographically representative South African cohort. There are concerns regarding the use of omeprazole as a probe drug as participants predicted to be ultrarapid metabolisers for CYP2C19 had similar rates to extensive metabolisers. Regardless of this concern, decreased metabolism was assigned to the CYP2C19*15 for the first time. CYP2D6 predicted phenotype correlated very well with measured phenotype, validating the suitability of dextromethorphan use for measuring CYP2D6 metabolism. Substrate modified activity score using 0.5 to predict intermediate metabolisers fine-tuned the XLPCR+ Sequencing platform for phenotype prediction. This finding, along with observations in CYP2C19 metabolism of omeprazole, highlights the importance of substrate specific phenotype prediction strategies. Controversially, attempts to associate CYP2D6 phenotype prediction with risperidone-related adverse drug reactions has yielded conflicting results. The XL-PCR+Sequencing platform was able to discount this association by predicting a variety of metabolisers in a pilot cohort selected to be experiencing risperidone-related adverse drug reactions. The comprehensive capability of the XL-PCR+Sequencing allowed for the identification of an additional novel allele in this cohort. The data presented in thisthesis has provided insight into the relationship between predicted and measured phenotype for CYP2C19 and CYP2D6 in the South African population. The XL-PCR+Sequencing platform can be used for future research or can be applied to improve treatment outcome. The LC-MS/MS method developed could be used for future evaluations of predicted and measured phenotype with the ability to be adjusted for therapeutic drug monitoring. This thesis advances pharmacogenetics of CYP2C19 and CYP2D6 for use in the South African population. / Thesis (PhD)--University of Pretoria, 2013. / gm2014 / Pharmacology / unrestricted

ANALYSIS OF DRUG-RELATED PROBLEMS IN A HEALTHCARE FACILITY V. Author: Thu Thao Truongová Supervisor of the diploma thesis: PharmDr. Martin Doseděl, Ph.D. Consultant: PharmDr. Veronika Měrková Charles University, Faculty of Pharmacy in Hradec Králové, Department of Social and Clinical Pharmacy INTRODUCTION Medication errors are one of the most frequent medicinal errors. They affect patient's safety from the long-term point of view.1 The great part of medication errors occurs on the level of drug administration.2 In healthcare facilities mostly nurses are responsible for medication administration.3 AIM To obtain and evaluate medication errors during drug administration by nurses in a healthcare facility. METHODICS A prospective observational study was conducted in the facility Hamzova léčebna for children and adults focusing on medical rehabilitation. Data collection was performed in May 2019 three consecutive days on each ward, where drugs were administrated by nurse. Direct observation was done in morning, noon and evening drug administrations. Obtained data were recorded into prepared form and were compared with physician's medication order on the patient's record. Afterwards, the forms were transcripted into online database, data were transfered to MS Excel software programme and evaluated by...

Innovation fuels American business. Commonly, innovation is judged as good. Yet, many of the new medical devices that come on the U.S. market every year are later deemed unsafe. Regulation is distorted in that 98% of medical devices are never evaluated in human trials before being introduced to the marketplace. Instead, the U.S. Food and Drug Administration (FDA) approves a new medical device through a designated 501(k) process, based upon the identification of a predicate or substantially equivalent (SE) device. This is an investigation of the tension between product innovation, government regulation, and public safety in the American healthcare industry. It is a research project in two parts. The first draws upon established methodologies and utilizes the FDA’s 501(k) database to provide an illustrated example of the sequence and dependency between generations of implanted surgical mesh devices. The analysis reveals that the 501(k) approval process reliance on predicate devices facilitates medical device innovation that is problematic in several aspects, including patient safety. To further examine medical device innovation and patient safety, the second study develops a proof-of-concept exercise to evaluate data on recorded adverse events (AEs) found in the FDA’s Total Product Lifecyle (TPLC) database for surgical mesh products. The adverse events were mapped to the Association for the Advancement of Automotive Medicine’s (AAAM’s) Abbreviate Injury Scale (AIS), following precedents found in the medico-legal literature and military injury biomechanics standards. This approach forges a path forward to determine the relative frequency and severity of adverse events of a specific medical device, compared to that of the overall FDA product category. These two research projects combine to contribute to the understanding of safety of the FDA’s approval process and by extension the medical device industry’s innovation practices. / Business Administration/Accounting