Dissertationen zum Thema „Medicinal Attributes“

Physician assistant (PA) program directors perform an essential role in the initiation, continuation, and development of PA education programs in the rapidly changing environments of both health care and higher education. However, only limited research exists on this academic leader. This study examined the leadership roles of PA program directors in the context of full-range leadership theory. This theory distinguishes between transformational, transactional, and passive/avoidant behaviors of the program director from the perspectives of both leader and follower. This study also examined leadership outcomes.

Data were collected via an electronic survey (Multifactor Leadership Questionnaire) administered to PA program directors and other members in the same academic unit. The survey was deployed to 82 academic units. The response rates for completed MLQ surveys were 43.2% (54) for program directors and 24.6% (228) for others associated with the PA academic unit.

The results of this study indicated that program directors use transformational leadership factors frequently in the execution of their responsibilities, and those program directors perceive favorable outcomes with these behaviors. However, discrepancies existed between leader perceptions and the perceptions of individuals in the same academic unit in regards to leadership and outcomes, with program directors having more favorable perceptions. This research provides a foundation for future study of the PA program director and contributes towards professional development efforts and the measurement of associated outcomes.

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This study aimed to evaluate the influence of esophageal motility parameters, the characteristics of gastroesophageal reflux, the presence of anxiety and depression, the presence of dyspeptic symptoms and the gastric emptying on the laryngeal symptoms (hoarseness, throat clearing and coughing) in patients with posterior laryngitis attributed to GERD. Initially, we studied 20 patients with posterior larynx and typical symptoms of GERD and 12 patients with erosive reflux esophagitis without laryngeal symptoms. All patients underwent upper endoscopy, high-resolution manometry and answered the questionnaire of GERD symptoms (QS-GERD) and the questionnaire about quality of life in GERD (QVRS-DRGE). Then, only the group of patients with laryngitis underwent 24 hours impedance-pH monitoring, answered Hospital Anxiety and Depression Scale (HADS) and the questionnaire of Porto Alegre of dyspeptic symptoms (PADYQ) and underwent gastric emptying breath test. All protocols were approved by the Research Ethics Committee of HUWC (14464214.8.0000.5045). Data were analyzed using the unpaired Student t test, Mann-Whitney and the correlation of Spearman. Endoscopy was normal in 85% of patients with laryngitis. The need to use medication had greater impact on the quality of life of the group with esophagitis, while the degree of dissatisfaction with their situation was significantly higher in patients with laryngitis. Patients presented with laryngitis had pressure of the lower esophageal sphincter and contractility of the esophageal body significantly larger than esophagitis group. There was no correlation between esophageal motility parameters with the frequency of laryngeal symptoms (hoarseness, throat clearing and coughing) in the laryngitis group. There was a positive correlation between the frequency of symptoms of hoarseness, throat clearing and coughing with the number of reflux measured by impedance-pH monitoring. This correlation was found only with weakly acidic reflux (4.0 6.5) for symptoms throat clearing and cough. There was a high prevalence of anxiety / depression in patients with laryngitis (50%), with a positive correlation between the intensity of anxiety and the frequency of hoarseness and , but not coughing. Patients with laryngitis showed a high prevalence of gastrointestinal symptoms (75%), but it was not observed delay in gastric emptying of solids in this group when compared to normal subjects. From this results we conclude that the laryngeal symptoms attributed to gastroesophageal reflux are associated with a greater degree of dissatisfaction with clinical situation and loss in quality of life; with the presence of weakly acidic or alkaline reflux and with anxiety. It was unrelated to endoscopic mucosal injury , changes in esophageal motility and gastric emptying .
Fatores associados aos sintomas larÃngeos atribuÃdos ao refluxo gastroesofÃgico em pacientes com laringite posterior. Cynthia Aben-Athar Ponte. Tese (Doutorado). Programa de PÃs-graduaÃÃo Stricto Sensu em CiÃncias MÃdicas. Orientador: Professor Doutor Marcellus Henrique Loiola Ponte de Souza. O presente estudo teve como objetivo avaliar a influÃncia dos parÃmetros de motilidade esofÃgica, das caracterÃsticas do refluxo gastroesofÃgico, da presenÃa de ansiedade e depressÃo, da presenÃa de sintomas dispÃpticos e do esvaziamento gÃstrico sobre os sintomas larÃngeos (rouquidÃo, pigarro e tosse) em pacientes com laringite posterior atribuÃda a DRGE. Inicialmente, foram estudados 20 pacientes com laringe posterior e sintomas tÃpicos de DRGE e 12 pacientes com esofagite erosiva de refluxo sem sintomas larÃngeos. Todos os pacientes realizaram endoscopia digestiva alta, manometria de alta resoluÃÃo e responderam ao questionÃrio de sintomas para DRGE (QS-DRGE) e o questionÃrio de qualidade de Vida Relacionada a Saude na DRGE (QVRS-DRGE). Posteriormente, somente o grupo de pacientes com laringite foram submetidos a impedancio-pHmetria de 24 horas, responderam a escala Hospitalar de Ansiedade e DepressÃo (HADS) e ao questionÃrio de Porto Alegre de Sintomas DispÃpticos (PADYQ), e realizaram o teste respiratÃrio de esvaziamento gÃstrico, sendo todos os protocolos aprovados pelo Comità de Ãtica em Pesquisa do HUWC (14464214.8.0000.5045). Os dados foram analisados utilizando os testes t de Student nÃo pareado, Mann-Whitney e a correlaÃÃo de Spearman. A endoscopia digestiva alta foi normal em 85% dos pacientes com laringite. A necessidade de utilizar o medicamento teve maior impacto sobre a qualidade de vida do grupo com esofagite, enquanto o grau de insatisfaÃÃo com a sua situaÃÃo foi significativamente maior no grupo com laringite. Os pacientes com laringite apresentaram pressÃes do esfÃncter esofÃgico inferior e contractilidade do corpo do esÃfago significativamente maiores que o grupo esofagite. NÃo houve correlaÃÃo entre os parÃmetros de motilidade esofÃgica com a freqÃÃncia dos sintomas larÃngeos (rouquidÃo, pigarro e tosse) no grupo laringite. Houve uma correlaÃÃo positiva entre a freqÃÃncia dos sintomas de rouquidÃo, pigarro e tosse com o nÃmero de refluxos aferidos pela impedancio-pHmetria. Esta correlaÃÃo foi encontrada apenas com os refluxos fracamente Ãcidos (4,0 < pH < 6,5) para o sintoma rouquidÃo; ou alcalinos (pH > 6,5) para os sintomas pigarro e tosse. Observou-se uma prevalÃncia alta de ansiedade/depressÃo nos pacientes com laringite (50%), com uma correlaÃÃo positiva entre a intensidade da ansiedade e a freqÃÃncia de rouquidÃo e pigarro, mas nÃo tosse. Os pacientes com laringite apresentaram uma grande prevalÃncia de sintomas dispÃpticos (75%), porÃm nÃo foi observado retarde no esvaziamento gÃstrico de sÃlidos neste grupo quando comparado com indivÃduos normais. A partir deste resultados podemos concluir que os sintomas larÃngeos atribuÃdos ao refluxo gastroesofÃgico estÃo associados com um maior grau de insatisfaÃÃo com a sua situaÃÃo cÃnica e perda na qualidade de vida; com a presenÃa de refluxos fracamente Ãcidos ou alcalinos e com a presenÃa de ansiedade. NÃo houve relaÃÃo, porÃm, destes sintomas com lesÃes endoscÃpicas da mucosa; alteraÃÃes na motilidade esofÃgica e com o esvaziamento gÃstrico.

Background: In the UK specialty trainees are a major source of clinical teaching for junior doctors. Medical education and teaching skills are core competencies included in the generic curriculum for specialist training. Hence, there is a need for a validated assessment instrument that can measure the attributes of specialty trainees as effective teachers, leading to the research question; Is it possible to devise an instrument to measure the teaching ability of specialty trainee doctors? Methods: The study was conducted in two phases. In the first phase, the content of the instrument was generated from the literature and tested using the Delphi technique. This was followed by pilot testing the instrument. In the second phase, the instrument was field tested for validity and reliability by conducting factor analysis, Cronbach alpha and Generalizability coefficient. The instrument was also tested for feasibility by calculating the time taken to complete the instrument. Acceptability and educational impact were determined by qualitative analysis of written feedback from participants. The attributes of specialty trainees were assessed by clinical supervisors, peers and students. Results: The Delphi study produced a consensus on 15 statements for the final draft of the instrument. This draft was piloted and finalised using feedback from that pilot. The instrument was field tested. In the field study a total of 340 instruments were completed. The instrument exhibited internal consistency (Cronbach’s alpha 0.90) and the Generalizability coefficient was 0.92. Factor analysis demonstrated a three factor solution (learning-teaching milieu, teaching skills and learner-orientated). The mean time to complete the instrument was five minutes. Feedback from participants indicated that it was an acceptable method of assessment, and trainees also found it useful for improving their teaching performance. Discussion: Findings from the present study suggest that this instrument demonstrates robust validity and reliability. It is feasible to use it in a busy clinical setting. It is acceptable by stakeholders which indicate that it can be used for assessment of teaching in clinical settings. Further specialty trainees found it useful, thereby indicating a positive educational impact. Conclusion: This new instrument, specifically designed to test the teaching attributes of doctors-intraining, can be useful for providing formative and summative assessment of clinical teaching.

Creating a database to manage medical data is not the easiest. We create a database to be used for a presentation tool that presents medical data about patients that is stored in the database. We examine which of the three databases, MySQL with relational design, MySQL with EAV design and MongoDB that are best suited for storing medical data. The analysis i performed in two steps. The first step handles the database that is most effective to retriev data. The second step examines how easy it is to change the structure of the various databases. The results show that depending on whether efficiency or maintenance is most important, different databases are the best choise. MySQL with relational design proves to be most effective while MongoDB is the easiest to maintain.

The use of electronic health records (EHR) has the potential to improve relationships between physicians and patients and significantly improve care delivery. The purpose of this study was to analyze the relationships between hospital attributes and EHR implementation. The research design for this study was the cross-sectional approach. Secondary data from the Health Information and Management Systems Society (HIMSS) Analytics Database was utilized (n = 169) in a correlational crosssectional research design. Normalization Process Theory (NPT) and implementation theory were the theoretical underpinnings used in this study. Multiple linear regressions results showed statistically significant relationships between the 4 independent variables (region, ownership status, number of staffed beds [size], and organizational control) and the outcomes for the dependent variables of EHR software application attributes (Clinical Decision Support Systems (CDSS) components), EHR software application attributes (major systems), and successful implementation of Meaningful Use (MU) (p = .001). A statistically significant relationship (p = .001) was also found between the 2 independent variables (EHR software application attributes [CDSS components] and EHR software application attributes [major systems]) and the outcome of successful implementation of MU when combined. This evidence should provide policy makers and health practitioners support for their attempts to implement EHR systems to result in positive Meaningful Use which has been shown to be more cost effective and result in better quality of care for patients.The potential social change is improved medication prescribing and administration for hospitals and, lower cost and better quality of care for patients.

[Truncated abstract] In this thesis, we introduce a mammogram analysis system developed for the automatic segmentation and analysis of mammograms. This original system has been designed to aid radiologists to detect breast cancer on mammograms. The system embodies attribute-driven segmentation in which the attributes of an image are extracted progressively in a step-by-step, hierarchical fashion. Global, low-level attributes obtained in the early stages are used to derive local, high-level attributes in later stages, leading to increasing refinement and accuracy in image segmentation and analysis. The proposed system can be characterized as: • a bootstrap engine driven by the attributes of the images; • a solid framework supporting the process of hierarchical segmentation; • a universal platform for the development and integration of segmentation and analysis techniques; and • an extensible database in which knowledge about the image is accumulated. Central to this system are three major components: 1. a series of applications for attribute acquisition; 2. a standard format for attribute normalization; and 3. a database for attribute storage and data exchange between applications. The first step of the automatic process is to segment the mammogram hierarchically into several distinctive regions that represent the anatomy of the breast. The adequacy and quality of the mammogram are then assessed using the anatomical features obtained from segmentation. Further image analysis, such as breast density classification and lesion detection, may then be carried out inside the breast region. Several domain-specific algorithms have therefore been developed for the attribute acquisition component in the system. These include: 1. automatic pectoral muscle segmentation; 2. adequacy assessment of positioning and exposure; and 3. contrast enhancement of mass lesions. An adaptive algorithm is described for automatic segmentation of the pectoral muscle on mammograms of mediolateral oblique (MLO) views

The purpose of this study was to evaluate the influence of facial convexity on the perception of social attributes in a young adult population. Nine models were asked to pose for a 3 dimensional photograph that was then modified to represent ideal, retrognathic, and prognathic facial convexity angles. Survey evaluators were shown digital videos of models with ideal and non-ideal profiles and asked to rate their perception of the following 4 social attributes: intelligence, athleticism, popularity, and leadership ability using a visual analog scale. Results gathered from 271 evaluators showed that the model images with ideal facial convexity angles were rated higher on average than the same model images with retrognathic and prognathic profiles. The differences in ratings between ideal and non-ideal profiles were significant for intelligence (P = 0.0009), athleticism (P = 0.0002), and leadership ability (P = 0.0008). Differences in perceived popularity (P = 0.2169) showed no significant differences among facial convexities.

Research intentionally addressing how leadership attributes and behaviors collectively contributed to the socioecological perspective of organizational resilience were not found. This is a problem for organizations who must hire without benefit of how a collective leadership effect might influence their psychological capital. The purpose of this study was to explore whether or not self-efficacy, psychological empowerment, personal resilience, and leadership style were associated with or predicted organizational resilience among clinical managers in an academic medical center setting. Metatheory of resilience and resiliency was used to frame the study. A quantitative correlational design was used. Self-reported data was collected via the Leader Efficacy Questionnaire, Psychological Empowerment Instrument, Connor and Davidson's Resilience Scale, Multifactor Leadership Questionnaire, and Workplace Resilience Instrument. Intellectual stimulation (rs .480, Ï? .432, p = .00), personal resilience (rs .483, Ï? .465, p = .00), and self-efficacy (rs .522, Ï? .462, p = .00) had the highest statistical correlations to organizational resilience. Negative predictor effects were found for personal resilience and idealized attributes ascribed to self-oriented versus other-oriented resilience qualities, x2(2) = 50.70, p < .01, and p < .05 respectively. Resilience is important for organizational survival and adaptation to the external and internal forces of change. Resilient organizations with available reserves can collaborate with community leaders to optimize the social, environmental, and economic determinants of health foundational for community resilience and positive social change.

According to a growing body of research, gender stereotypes can have a profound effect on hiring decisions. However, it is unclear whether information confirming or contradicting gender stereotypes can bias recruiters’ memory and ultimately affect hiring decisions. This study examined whether gender stereotypes about job applicants can affect memory of recruiters to remember stereotype consistent information, specifically when hiring for a predominantly male gender-typed job position as Financial Advisor. In a true experiment, 158 participants screened CVs of fictitious applicants, containing either gender stereotype consistent or inconsistent information in an online hiring scenario conducted mainly through a professional social network site. Recognition of consistent and inconsistent information was measured, as well as the intent to hire and to invite the applicant for a job interview. The results revealed that stereotype consistent information on the CV was not remembered more than stereotype inconsistent information. Additionally, male applicants were not preferred over female applicants in regard to the intent to hire. Female applicants were more likely to be invited for an interview than male applicants, as opposed to our hypothesized presumption. Professional experience in personnel selection did not affect the results. Practical implications are discussed.

The purpose of this study was to determine the influence of dentofacial appearance on perceived social attributes of college-aged adult males and females as judged by their peers. Specifically, the objective was to determine if ideal smile esthetics positively influenced this age group’s perception of opposite-sex peers based on ratings of the following psychosocial characteristics: attractiveness, desire to spend time with, desire to date, and desire for a long-term relationship. Evaluators were shown digital photographs of subjects with ideal and nonideal smiles and asked to rate those 4 attributes using a visual analogue scale (VAS). The subjects’ photographs with ideal smile esthetics were consistently rated higher on average than the same subjects’ photographs with nonideal smile esthetics. The differences in ratings between ideal and nonideal smile images were significant for all 4 psychosocial judgments (P <.0001). These differences ranged in magnitude depending on the sex and race of the evaluator and subject.

Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, 2009.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 69-73).
Personalized medicine is the science and practice of customizing medical screening and treatment plans for an individual based on his or her genomic profile. Breast cancer is one of the first disease areas to serve as an example of this approach, where most patients have experienced its benefits through the use of genetic tests that provide decision support for health care workers regarding the likely effectiveness of specific drugs and, more broadly, the urgency of particular treatment options (for example, chemoprevention versus prophylactic surgery). Little is known about the diffusion of such personalized approaches to medical practice, particularly the factors shaping the adoption of genetic tests. While numerous medical diffusion studies have been published over the past few decades, most were univariate analyses and did not consider the unique aspects of genetic testing versus drugs. Moreover, they mainly focused on the characteristics and behaviors of physicians, patients, product manufacturers, and social networks, and did not explore the role of potentially important third parties like professional medical societies and patient groups (e.g. disease foundations and patient advocacy organizations). The aim of this thesis was to analyze the relationship between seven attributes of four breast cancer genetic tests and clinical adoption to show that standard diffusion frameworks can be enhanced through previously unstudied dimensions when evaluating personalized medicine-related innovations.
(cont.) We identified four variables that correlated with clinical adoption: 1) regulatory status, 2) inclusion in practice guidelines by professional societies, 3) explicit endorsement by patient groups, and 4) implicit endorsement by patient groups. Our findings indicate that a key overlooked element in the current literature (and potentially overlooked by the firms creating these tests) is the role of patient groups in the diffusion of novel genetic tests, in addition to endorsement from medical professional societies. These findings may add value to strategic decisions made by company executives, investors, payers, health care providers, and patients as they are presented with novel products and development opportunities in the era of personalized medicine.
by Julie Keunhee Yoo.
S.M.

Gli strumenti fino ad ora disponibili hanno fallito nel tentativo di predire gli eventi avversi dei pazienti con sincope in pronto soccorso. Per valutare i possibili punti di forza e di debolezza e confrontare i diversi metodi statistici usati per la derivazione di score e scale di rischio, abbiamo deciso di derivare dei modelli basati su regressione logistica multivariata e reti neurali artificiali (ANN) a partire da un database retrospettivo e di validarli in un nuovo dataset di 354 pazienti. L’area sotto la curva ROC di regressione multivariata e ANN è risultata rispettivamente di 0.726 e 0.694 nella coorte di validazione. Vista la bassa accuratezza predittiva dei modelli analizzati, abbiamo provato a identificare metodi alternativi per predire il rischio di eventi avversi dei pazienti con sincope. Abbiamo ipotizzato che si potesse stimare una probabilità pre-test accurata appaiando ogni singolo paziente ad un gruppo di pazienti con le stesse caratteristiche cliniche, e valutando la proporzione che aveva sviluppato l’outcome di interesse (attribute matching). In teoria, il funzionamento ideale di tale sistema consentirebbe di confrontare un profilo clinico tanto più dettagliato e di avere stime di rischio molto precise quanto più il database di riferimento è ampio. Pertanto, questo strumento non è ancora utilizzabile nella pratica clinica, ma sembra un metodo promettente. Studi futuri dovrebbero costruire database prospettici che arruolino un gran numero di pazienti per valutare se l’attibute matching possa aggiungere informazioni agli strumenti predittivi tradizionali e alla stima del rischio da parte di medici esperti. Inoltre, la possibilità di introdurre variabili nuove e sempre più complesse e di poter predire nel dettaglio diversi tipi di outcome, potrebbe creare un profilo clinico più specifico e potenzialmente sempre più accurato.
Clinical prediction tools have failed in the correct risk stratification of syncope patients in the emergency department. To assess the possible strengths and weaknesses and to compare the different statistical methodologies to derive prediction tools, we decided to derive both a multivariate logistic regression model and an artificial neural network (ANN) on a large retrospective database and to prospectively validate them in a new dataset of 354 patients. The area under the ROC curve of multivariate regression and ANN in the validation cohort were 0.726 and 0.694, respectively. Since the poor predictive accuracy of the analyzed models, we tried to identify alternative methods. We hypothesized that accurate pretest probability assessments can be obtained by matching an individual patient to a group of previously studied patients who shared the same clinical characteristic and determining the percentage of these previously studied patients who had the outcome of interest. In theory, the ideal attribute matching system would allow a very detailed clinical profile to be matched against a very large reference database to provide accurate risk estimates. Therefore, we do not offer a clinically useful prediction tool at this stage, but this method seems promising. Future studies should focus on building large prospective datasets to assess if attribute matching adds any value to both the traditional clinical decision tools and the implicit estimate of probability from clinicians. Moreover, the introduction of new and more complex input attributes and the possibility to provide as output a detailed risk assessment will create a more specific and potentially more accurate clinical profile.

The complex nature of healthcare requires nurse leaders to be skilled in professional practice, communication, teamwork, and problem solving to improve staff satisfaction and patient outcomes. The American Association of Colleges of Nursing and Institute of Medicine promotes graduate education for nurse leaders to enhance the delivery of quality care to the nation's diverse patient populations. Guided by the diffusion of innovation theory, this project explored the differences in nursing care hours, staff turnover, nurse quality indicators, as well as leadership characteristics on units lead by masters-prepared and non-masters-prepared nurses. Forty-eight nurse leaders completed the impact of graduate education among nurse leaders (IGENL) survey addressing perceptions of their ability to change practice, teamwork, communication, and problem-solving skills. Staffing reports, Nurse Quality Indicators (NQI), and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) data were collected from 34 hospital units. Data were summarized and t tests were conducted to examine the differences in NQI and HCAHPS data from units lead by nurses with and without a graduate degree. No significant differences were noted in these measures. In the IGENL survey data, the nurse leaders with a graduate degree had significantly higher scores on the leadership characteristic subscales of professional practice, communication and teamwork, and problem solving than did those without. The outcome of this project can contribute to positive social change within healthcare organizations by supporting the pursuit of graduate education for nurse leaders, which could enhance leadership attributes and subsequently improve staff satisfaction and patient outcomes.

Mesenchymal stem/ stromal cells (MSCs) have been proved to be capable to modulate the immune system through direct interactions target cell-MSC and secretion of soluble molecules that are induced or upregulated following cross-talk with target cells. In this study, a full biological characterization of ImmuneSafe® (IS) features including identity, potency and safety which constitute the Critical Quality Attributes (CQAs) of the product was performed with purpose of providing tools that will assure the consistency and robustness of the manufacturing process or demonstrating product/ process comparability after a particular change in the manufacturing process. In order to achieve this goal a (bio) assay panel was developed and applied to IS in two different steps of manufacturing process. IS CQAs allowed a robust and reproducible characterization of the product, demonstrating their potential to be used throughout the production stage. Similar studies were also performed with similar cell types, such as human skin fibroblasts and MSCs differentiated in adipocytes and osteocytes, which were then benchmarked with IS. The results showed that none of these cell types demonstrated a comparable level of therapeutic potency to IS. The patient enrolling protocol for IS clinical trial to treat GvHD will include the administration of immunosuppressive drugs (methylprednisolone or prednisolone) concomitantly with IS administration. The impact of these drugs on IS identity was evaluated through immunophenotype characterization and potency was evaluated through the activation of the different immunomodulatory pathways. The results showed that immunosuppressive drugs tested, methylprednisolone and prednisolone, did not seem to have a beneficial or detrimental interaction with IS. MSCs are commonly stored in cryopreservation conditions before the deliver to the patient. However, recent studies have shown that banked fresh thawed MSCs have impaired immunomodulatory properties compared to MSCs in culture. IS response to an inflammatory microenvironment was compared in different times of release and fresh thawed cells revealed to have several responses compromised under pro-inflammatory environment. Additionally, IS secretome was also affected, since the production of several cytokines were decreased or even switched off, as well as the immunosuppressive activity of the product. For these reasons the implementation of a release culture step was found to be advantageous in order to maximize the therapeutic potency of IS. Another important issue for cell-based therapies is the product delivery to the hospital. Cells should be formulated in a suitable excipient for intravenous infusion capable of maintaining the cell viability and therapeutic potential during the purposed product shelf-life. For this purpose IS was formulated in a saline solution and identity and potency tests were performed. Hypothermosol was capable of maintaining at least 70% of initial cell number population with 80% of viability, as well as its identity and potency features within a 48h-window. These studies enable a comprehensive IS characterization and the set-up of the assays to be used in the manufacturing process under GMP conditions. Additionally, no detrimental effects on the therapeutic potency of IS were associated with the interactions with the immunosuppressive drugs that will be used in the clinical trial, thus indicating the clinical results will not probably be affected by the background therapy applied to patients. The process of product release was also optimized to guarantee a cell product with maximized immunomodulatory properties and a 48-hour shelf-life was determined, which is a critical issue for the planning of IS logistics for the clinical trial.

碩士
國立宜蘭大學
人文及管理學院高階經營管理碩士在職專班
107
In a highly competitive market environment, pharmaceutical companies must continually optimize the formulations, packaging, marketing, services, brands and images to improve organizational performance, and Consumer-oriented marketing is the key for today's pharmaceutical companies to discover new customers. Packaging of medicines, as the first link of communicating with consumers, plays an critical role in marketing and operations. Therefore, how to improve the quality of pharmaceutical packaging to meet consumers’ needs and retain consumers is an important issue of pharmaceutical companies. The target group of this study is the consumers who have purchased or taken OTC drugs which are manufactured by Sinphar. The customer-oriented packaging quality questionnaire is designed from the relevant literatures on packaging design and expert interviews. Kano model and Refined Kano's model are used in this study to classify packaging quality factors. In conjunction with the impact comparison and analysis between different demographic variables, and the distribution situation of drug packaging guality in the importance-satisfaction model, this study aims to find out what are the factors that consumers consider for the quality of pharmaceutical packaging. The reference for the pharmaceutical industry to improve the quality and strategy of future pharmaceutical packaging can be provided correspondingly. The results of this study shows that packaging structure and marketing considerations are two dimensions of packaging quality that respondents consider important and have to be improved. Among selected 18 elements of packaging quality, anti-counterfeiting functionality, child-safety packaging, and memory are identified as the top three elements that need to be improved base on the result of importance analysis, Kano model, Refined Kano’s model, and I-S model. Furthermore, this study proposes a priority and appropriate packaging improvement program for Sinphar pharmaceutical company as a reference for product packaging design, and expects to achieve maximum benefit improvement within limited resources.

碩士
國立臺灣科技大學
企業管理系
104
The implementation of NHI (National Health Insurance) brought great change on medical and pharmaceutical industry. The scale of pharmaceutical market has been revised down, and the high-priced self-paid medicin become the developing and marketing direction in recent years. Open markets and the popularity of medicine information, patients (customers) for the medicine to have more autonomy and selectivity.Pharmaceutical companies play a more active role in the overall self-paid medical activities. Marketing objectives by a physician for the center change into by the self-paid medicine purchaser for the center. In addition to the promotion as"push" strategy, they also conduct the promotion of public relationship as "pull" strategy. A review of the previous relevant studies, focused on marketing promotion of prescription behavior of physicians, mostly prescribing medicine.Only few issues about self-paid medicine purchasers are discussed. Rarely discuss both and expected quality medical personnels and patients are the same? The aim of the study is to explore and compare the gaps of recognition for the service quality between medical professionals and patients on self-paid medicine marketing with Kano model and Refined Kano model as the foundation. The questionnaires were designed based on adopting the two-dimensional Kano quality model and the three dimensions with 16 items which aim to assess the quality of self-paid medicine services in terms of the marketing mix of product strategy and promotion strategy. The results are as follows: There are statistically significant differences between the medical professionals and patients in most items assessing quality elements and degree of importance. Using Kano model, there is 12 items one-dimensional quality in patients, but there is 9 items indifferent quality in medical professionals. Using Refined Kano model, there is 8 items high value-added and 3 items Care-free in patients, but there is 5 items high value-added and 6 items Care-free in medical professionals.The results have shown that customers really expect the quality is higher than expected medical professionals perceived customer expected the quality. There is only one item fall in the improved area, this also belong to the top one Improvement index.The results can be used by Pharmaceutical companies to develop marketing strategy on self-paid medicine and to improve service quality and satisfaction to achieve medical professionals and customers to win-win.

As cefaleias e a dor facial são comuns na população em geral. Em muitos casos, a dor facial pode ser manifestação de disfunções temporomandibulares (DTM). O objetivo desta revisão bibliográfica narrativa foi analisar a relação entre as cefaleias primárias e a cefaleia atribuída à DTM, avaliando os critérios mais recentes de diagnóstico, a fisiopatologia e suas relações, bem como, a sua importância no âmbito da consulta de medicina dentária. A pesquisa bibliográfica foi limitada aos últimos 10 anos, no total 41 referências foram consultadas. A literatura tende a mostrar uma relação bidirecional entre cefaleia primária e cefaleia atribuída a DTM e da fisiopatologia e relações neuroanatómicas comuns, no entanto, os critérios para classificação das cefaleias atribuídas à DTM ainda não são claros, pelo que mais estudos devem ser realizados. O médico dentista deve fazer parte da equipa de diagnóstico das cefaleias quando estas são afetadas/agravadas pela função do sistema estomatognático.
Headache and facial pain are common in the general population. In many cases, facial pain can be a manifestation of temporomandibular disorders (TMD). The aim of this narrative literature review was to analyze the relationship between primary headaches and headache attributed to TMD, evaluating the most recent diagnostic criteria, pathophysiology and their relationships, as well as their importance in the context of dental consultation. The bibliographic search was limited to the last 10 years, a total of 41 references were consulted. Literature tends to show a bidirectional relationship between primary headache and headache attributed to TMD and pathophysiology and common neuroanatomical relationships, however, the criteria for classification of headaches attributed to TMD are not yet clear, so further studies should be carried out. The dentist should be part of the diagnostic team for headaches when they are affected/aggravated by the function of the stomatognathic system.

Tese no âmbito do Doutoramento em Ciências Farmacêuticas, ramo de Tecnologia Farmacêutica, apresentada à Faculdade de Farmácia da Universidade de Coimbra.
Solid dispersions are systems where one component is dispersed in a carrier, and the whole system is solid. The solubility, drug release, chemical and physical stability, and in vivo performance of these compositions vary depending on the chemical characteristics of the main components and the physical structure of the composition. Solid dispersions are considered one of the most complex pharmaceutical systems, and an in-depth understanding of their properties is essential to control and modulate product performance. The use of Hot-melt extrusion (HME) to prepare solid dispersions has made it a technology that changed the entire paradigm of the pharmaceutical industry research and manufacturing. It is recognizably able to overcome formulation barriers and tailor drug performance and has been used successfully for already marketed products and many others under development. The enhancement of solubility is the primary use of HME, but others include taste-masking, stabilization of amorphous drugs, and controlled drug delivery. In this work, HME technology was applied in three different scopes, particularly in the solubility enhancement of a poorly soluble compound, in the physical stabilization of an unstable amorphous drug, and in the controlled release of a highly soluble drug in low drug load. A combination of chromatographic (high and ultra performance liquid chromatography (HPLC and UPLC)), microscopic (optical microscopy, polarized light microscopy (PLM), scanning electron microscopy (SEM)), thermal (standard differential scanning calorimetry (DSC), modulated temperature DSC (mDSC), thermogravimetric analysis (TGA), and polarized light thermal microscopy (PLTM)), diffraction (X-ray powder diffraction (XRPD)), and spectroscopic techniques (Raman spectroscopy coupled to confocal microscopy, or in some cases to variable temperature) were used. Dissolution testing and stability studies were as well crucial for the in-depth characterization of the prepared systems. High-throughput screening methods, thermodynamic predictions, and statistical analysis were also of great importance. In this work, a systematic step-by-step methodology for the development of solid dispersions was presented, where thermodynamics, screening approaches, multivariate statistics, and process optimization were combined (Chapter I). It was focused on pharmaceutical development under the Quality by Design principles and practical methods from early development to regulatory approval. The technical and scientific specificities of HME-based formulations were discussed in line with the state of the art of product development and current regulatory guidance. Then, an amorphous solid dispersion (ASD) of Etravirine was prepared to enhance the solubility of this poorly soluble drug (Chapter II). An extensive investigation of the solubilization capacity and physical stability of different compositions was performed, where theoretical predictions, high-throughput screening, and Principal Components Analysis were combined. The dissolution rate was improved more than two times, and the ASD demonstrated to be physically and chemically stable for at least three months, even when stored at accelerated conditions. Although not expected, it was later explained by Raman spectroscopy, where molecular interactions affecting the CN groups of Etravirine were observed. Moreover, Raman's high potential to distinguish solid-state forms was demonstrated, including differentiating amorphous and crystalline states. A different aim of the investigation was described in the Ibrutinib research (Chapter III), where HME was applied to improve the physical stability of the amorphous drug. Although with a high tendency to convert into the most stable crystalline form, stability until at least six months at accelerated conditions was achieved through HME in a very high drug load of 50%. Intermolecular interactions characterized by thermal analysis and Raman spectroscopy involving the α, β unsaturated ketone of ibrutinib supported the physical strength of the prepared systems. This application of HME technology is not common but demonstrated a remarkable interplay between HME, drug loading, polymeric carriers, solid state, and intermolecular interactions that can also be applied to other drugs. Lastly, the well-known technological challenge of controlling the release of a highly soluble drug was overcome through an innovative platform involving HME (Chapter IV). The selected prototype is not standard in the field and consists of microtablets tableted into tablets, where HME is coupled with double compression as downstream processing. Its performance was exhaustively characterized, and near zero-order kinetics for 6 to 8 hours observed on dissolution. The mechanistic drug release was explored through the Weibull function and SEM, and revealed a combination of swelling, diffusion, and erosion. The research performed had several goals, but it is possible to stand out the overcome of formulation barriers, tailoring challenging drug properties through the use of the potentialities of HME. Also important is the contribution to an improved understanding of the complex solid-state characterization of solid dispersions, including physicochemical properties of drugs and formulated systems. However, further efforts and expertise are still required to achieve the purpose of this work. The research identified gaps, challenges, and future areas of study to, finally, take these products - better products - to market.
As dispersões sólidas são sistemas em que um determinado componente está disperso num veículo, e o sistema existe no estado sólido. A solubilidade, dissolução do fármaco, estabilidade física e química, e comportamento in vivo destas formulações varia consoante as características químicas dos componentes principais e a estrutura física da composição. As dispersões sólidas são consideradas um dos tipos de sistemas farmacêuticos mais complexo, e a caracterização profunda das suas propriedades é essencial para controlar e modular o comportamento do produto. O uso da extrusão a quente fez com que o paradigma da investigação e fabrico na indústria farmacêutica fosse completamente alterado no que concerne à preparação de dispersões sólidas. Esta tecnologia é reconhecidamente capaz de ultrapassar barreiras de formulação e modular a performance de fármacos, e tem sido utilizada com sucesso em produtos já comercializados e muitos outros em desenvolvimento. A utilização principal da extrusão a quente é a melhoria da solubilidade, mas pode ser também aplicada para mascarar o sabor, estabilizar fármacos amorfos ou para a libertação controlada de substâncias ativas. Neste trabalho, a tecnologia de extrusão a quente foi aplicada em três contextos diferentes, nomeadamente, na melhoria de solubilidade de um fármaco pouco solúvel, na estabilização do estado físico de uma substância amorfa reconhecidamente instável, e na libertação controlada de um composto altamente solúvel e de baixa dosagem. Para isso, foi utilizada uma combinação de técnicas cromatográficas (cromatografia líquida de alta e ultra eficiência (HPLC e UPLC)), microscópicas (microscopia ótica, microscopia de luz polarizada (PLM), microscopia eletrónica de varrimento (SEM)), térmicas (calorimetria diferencial de varrimento convencional (DSC) e com modulação de temperatura (mDSC), análise termogravimétrica (TGA), e microscopia térmica com luz polarizada (PLTM)), difração (difração de raios X de pó (XRPD)), e espectroscópicas (espectroscopia Raman acoplada a microscopia confocal e combinada, em alguns casos, com variação de temperatura). Os ensaios de dissolução e estudos de estabilidade foram também críticos para a caracterização detalhada dos sistemas preparados. Os métodos de rastreio de alto rendimento, os cálculos termodinâmicos e a análise estatística foram também importantes para o sucesso da investigação. Neste trabalho, foi apresentada uma metodologia sistemática passo-a-passo para o desenvolvimento de dispersões sólidas, onde se combinou a termodinâmica, as estratégias de rastreio, a estatística multivariada e a otimização de processos (Capítulo I). O foco foi o desenvolvimento farmacêutico segundo os princípios de Quality by Design e abordagens práticas, desde os primeiros estudos de desenvolvimento até à aprovação regulamentar. As especificidades técnica e científica das formulações baseadas em extrusão a quente foram discutidas, em linha com o estado da arte do desenvolvimento de produtos farmacêuticos e atuais diretrizes regulamentares. Posteriormente, foi preparada uma dispersão sólida amorfa (ASD) de Etravirina, para melhorar a solubilidade deste fármaco considerado pouco solúvel (Capítulo II). Foi feita uma investigação extensiva da capacidade de solubilização e estabilidade física de composições diferentes, onde se combinaram cálculos termodinâmicos, com o rastreio de alto rendimento e a análise de componentes principais. A taxa de dissolução foi melhorada mais de duas vezes, e a dispersão amorfa demonstrou ser física e quimicamente estável por, pelo menos, três meses, mesmo quando armazenada em condições aceleradas de envelhecimento. Este resultado foi explicado posteriormente através da espectroscopia Raman, onde foram observados sinais de interações intermoleculares nos grupos CN da Etravirina. Foi ainda demonstrado o alto potencial da espectroscopia Raman para distinguir diferentes estados sólidos, nomeadamente para diferenciar o estado amorfo do cristalino. Na investigação aplicada ao Ibrutinib (Capítulo III), o alvo da análise foi distinto e a extrusão foi aplicada para melhorar a estabilidade física de um fármaco no estado amorfo. Apesar de apresentar uma tendência elevada para conversão para o estado cristalino mais estável, foi possível atingir seis meses de estabilidade em condições aceleradas através do uso da extrusão a quente, mesmo utilizando uma elevada quantidade de fármaco na formulação, 50%. A análise térmica e espectroscópica permitiu detetar interações intermoleculares na cetona α, β-insaturada do Ibrutinib, que justificam a resiliência física dos sistemas preparados. Esta aplicação da extrusão não é comum, mas permitiu estabelecer uma relação notável entre extrusão a quente, quantidade de fármaco, excipientes, estado físico e interações intermoleculares, que poderão ser aplicadas a outros compostos. Por último, um conhecido desafio da tecnologia farmacêutica - a libertação de um fármaco muito solúvel em baixa dosagem - foi também ultrapassado, através da criação de uma plataforma tecnológica inovadora baseada na extrusão a quente (Capítulo IV). O protótipo selecionado não é considerado padrão na área, e consiste em microcomprimidos num comprimido, onde a extrusão é acoplada a jusante a uma dupla compressão. O comportamento deste sistema foi exaustivamente caracterizado, tendo-se observado, em dissolução, uma cinética próxima de ordem-zero durante 6 a 8 horas. O mecanismo de libertação foi também explorado através da função de Weibull e SEM, revelando a combinação de intumescimento, difusão e erosão. A investigação realizada teve vários objetivos, destacando-se a transposição de barreiras de formulação, através da modulação de fármacos difíceis recorrendo às potencialidades da extrusão a quente. Não menos importante, contribuiu para uma melhor compreensão da caracterização complexa do estado sólido de dispersões sólidas, incluindo propriedades físico-químicas de fármacos e seus sistemas formulados. No entanto, ainda se verifica a necessidade de esforço e especialização adicionais, de modo que seja atingido o desígnio deste trabalho. Foi possível identificar lacunas, desafios e eventuais áreas de investigação futura para, finalmente, levar os produtos - melhores produtos - até ao mercado.
Bluepharma - Indústria Farmacêutica, S.A. (Portugal)