M.Tech. (Chiropractic) / Please refer to full text to view abstract

BACKGROUND: Now considered a cornerstone of healthcare, patient-provider communication has long been studied and analyzed. Medical associations such as the Joint Commission and the American Association of Orthopaedic Surgeons (AAOS) have strongly endorsed for physicians to exercise patient-focused communication, a practice that involves showing empathy, involving patients in medical care decisions, eliciting concerns, and educating patients on treatment options (Joint Commission, 2016; AAOS, 2017). A lack of patient-provider communication has previously been identified as a significant factor in adverse medical outcomes occurring within hospitals (Khan et al., 2017). Bridging the communication disparity between patients and providers is crucial to improving overall patient outcome. Primary care providers are especially essential to improving overall patient outcome because they serve as the first point of contact for many patients accessing the healthcare system. While there is much literature on the importance of effective patient-provider communication, few studies provide technology-based tools that can enhance this establishment of communication. Human Papillomavirus is presently the most common sexually transmitted infection (STI) nationwide with 79 million Americans currently infected (CDC, 2017). Approximately 42,700 HPV-attributable cancers are diagnosed in the United States annually, and HPV is believed to be responsible for over 90% of cervical cancer cases (CDC, 2018). The Advisory Committee on Immunization Practices (ACIP) currently recommends three preventative HPV vaccines. Despite high rates of infection, HPV vaccination rates nationwide remain low as coverage of the HPV vaccine falls behind that of coverage for required vaccines like the tetanus, diphtheria, and acellular pertussis vaccine (Tdap) (Reagan-Steiner, 2016). Previous studies have sought to address factors that affect decisions to vaccinate children. An analyzation of the National Immunization Survey of Teens has identified that parents’ belief that the HPV was not necessary as a main factor (Darden et al., 2013). As a result, there is a gap needed to be filled by providers to educate parents on the importance of the HPV vaccine. PURPOSE: The current study sought to determine the effectiveness of a web-based mobile health education program called Wheel of Wellness (WoW) on patient-provider communication, to assess the viability and impact of WoW to increase HPV vaccination rates in age eligible children (boys and girls aged 9-17) and to augment awareness about the benefits of HPV vaccination in both these children and their guardians. RESEARCH METHOD AND DESIGN: As of August 2018, twenty-seven parents of children between the ages of 9 and 17 years of age within the Pediatrics and Adolescent departments of Boston Medical Center (BMC) have been recruited. Parents enrolled in the WoW program to compile a list of concerns to be shown to a provider during their child’s appointment. Participants were asked questions to determine initial knowledge on the HPV vaccine, and their opinions on the HPV vaccine. Following their appointment, participants completed a questionnaire to assess opinions on the WoW program in facilitating communication with their provider on the HPV vaccine and related cancers. Seven physicians were interviewed to assess their views on the WoW program in facilitating communication with their patients on the HPV vaccine and related cancers. RESULTS: Initial stages of this study found that views on the effectiveness of the WoW program in facilitating patient and provider communication on the different aspects of HPV vaccination and affecting parents’ decisions to vaccinate their children were mixed by both patients and their providers. Based on the WoW feedback collected from parents, the system was widely acceptable in terms of ease in usage and with the majority of parents (92%) reporting that the WoW website is helpful for communicating their health concerns with their provider. However, the majority of providers reported having never been presented the WoW system and expressed views that WoW was inefficient as it was a parallel system to existing workflow. This study determined that of the 12 participants who had one dose of the vaccine prior to enrollment, 75% of these participants completed the HPV vaccine series during the study. CONCLUSION: Based on the initiation and completion statistics reported, this shows great potential for the use of the BNI coupled with the WoW system to help improve rates of initiation and completion of HPV vaccination going forward as the intervention may have helped encourage parents to either initiate vaccination or complete their child’s previously started series. Further studies should explore ways of empowering patients to facilitate more communication with their providers and improvements to technology to enhance provider recommendation in order to promote an increase in HPV vaccine completion. / 2021-06-17T00:00:00Z

Department of Obstetrics and Gynaecology University of the Witwatersrand Johannesburg February 2015 A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Masters in Medicine, in the branch of Obstetrics and Gynaecology. / HIV accelerates the development of cervical cancer by up to15 years. South Africa is currently in the midst of an HIV epidemic. With limited facilities for colposcopy it is vital to identify risk factors within the HIV positive population resulting in positive margins after Large Loop Excision of the Transformation Zone (LLETZ) and persistence of cytological abnormalities on follow-up Pap smears. Objective: The primary objective was to determine the patient risk factors, pre and during colposcopy and LLETZ biopsy, which resulted in the histological involvement of margins of the LLETZ biopsy and persistent cervical dysplasia on follow-up Pap smears. Secondary objectives included determining follow up rate of patients at the clinic as well as the correlation between the original Pap smear cytology grade and the histological grade found on histology of the LLETZ biopsy. Methods: A retrospective review of the files of HIV seropositive patients was done at the colposcopy clinic at Charlotte Maxeke Johannesburg Academic Hospital after the roll out of antiretroviral treatment for the period 1 April 2004 to 31 October 2012. Patients with abnormal pap smears during this time were referred to the colposcopy clinic where a colposcopy and LLETZ biopsies were done. Demographic and clinical data in regards to age, gravidity, contraception, CD4 count, antiretroviral usage, and referral time was collected. Data from the clinical description of the colposcopy and histology of the LLETZ biopsy was also collected. Patients followed up again after 6 months when a repeat pap smear was done. The results of these Pap smears were also collected. Data was then analysed and variate and multivariate logistical regression was used to find statistically significant correlations. Results: A total of 480 files were found to have complete clinical records. One hundred and sixty eight (42.71%) patients had both endo and ectocervical margins clear. Predictive factors for the involvement of endocervical margins was the doctor performing the procedure (p-value <0.01) cytology of the original Pap smear (p value <0.01) and the grade of histological abnormality found at time of LLETZ (p-value <0.01). The statistically significant predictive factors for ectocervical margin involvement was the visualization of the transformation zone at colposcopy (p-value <0.01), the size of lesion found at colposcopy (p-value <0.01), the use of combined oral contraceptive pill (OCP) (p-value 0.02) and the histological grade of abnormality found on the LLETZ biopsy. Age, parity, CD4 count, use of antiretroviral drugs, length of time from Pap smear to colposcopy and use of contraception other than OCP were not found to be statistically significant in our sample population for the involvement of either endo or ectocervical margins. Statistically significant risk factors for the recurrence of intraepithelial lesions on follow up Pap smear was having both endo and ectocervical margin involvement on histology (p-value 0.01) The Ectocervical margin alone was found to have a p-value of <0.01. Abnormal cytology on follow up Pap smear was found in 58.69% of patients. The follow up rate at the clinic was 46.04%. Correlation of cytological grade and histological grade of cervical intraepithelial neoplasm in our sample population was found to be adequate (p-value <0.01). Conclusion: Incomplete incision of the intraepithelial lesion was found to be a significant risk factor for the recurrence of cytological abnormality in patients undergoing LLETZ biopsy. Identifying patients at increased risk for recurrence is important to ensure close follow up in this patient population.

Este estudo clínico randomizado duplo-cego avaliou a efetividade da irradiação com o laser de Nd:YAG e de uma pasta de fosfosilicato de cálcio e sódio (NovaMin®) no tratamento da hipersensibilidade dentinária cervical (HDC). Após seleção dos pacientes, estes foram aleatoriamente designados para os grupos experimentais: 1. controle-placebo, 2. Pasta de fosfosilicato de cálcio e sódio - NovaMin® e 3. Laser de Nd:YAG (1W, 10Hz, 85J/cm2). A dor foi avaliada através de uma escala visual analógica de dor após estímulo evaporativo com jato de ar e estímulo tátil com sonda exploradora antes do tratamento (baseline) e após 5 minutos, 1 e 4 semanas. Quando o paciente apresentava mais de um dente com HDC, a média dos valores obtidos era considerada. A irradiação com laser de Nd:YAG foi realizada duas vezes no sentido mésio-distal e duas no sentido ocluso-gengival. A pasta contendo NovaMin® foi aplicada com taça de borracha em baixa rotação após 60 segundos em contato com os dentes. Pacientes do grupo placebo receberam simulações de cada tratamento. Os avaliadores e os pacientes desconheciam o tratamento aplicado, enquanto que o pesquisador que realizou os tratamentos desconhecia os resultados das avaliações de dor. Como os dados apresentaram distribuição normal, foram comparados pelo teste ANOVA de medidas repetidas 2 fatores. Todos os tempos experimentais demonstraram diminuição na dor em relação ao baseline (p<0,05) e não houve diferença entre os grupos experimentais em nenhum dos tempos avaliados (p>0,05). Todos os tratamentos foram igualmente efetivos na diminuição da dor da HDC. / This double-blind randomized clinical trial assessed the Nd:YAG laser and calcium sodium phosphosilicate (NovaMin®) prophy paste effect in the treatment of cervical dentin hypersensitivity (CDH). The study consisted on three experimental groups: 1. Control-placebo, 2. calcium sodium phosphosilicate prophy paste - NovaMin® and 3. Nd:YAG Laser (1W, 10Hz, 85J/cm²). Pain was evaluated through a visual analogue scale (VAS) after evaporative stimuli with air blast and tactile stimuli with exploratory probe at baseline and after 5 minutes, 1 and 4 weeks. A simple mean was calculated for each patient, using individual results. Nd:YAG laser was irradiated twice at mesio-distal direction and twice at occluso-gingival direction. Prophylaxis using NovaMin® was performed 60 seconds after paste was applied. Patients from control group received each treatment simulation. Both patients and evaluators did not know the administered treatment, as the principal researcher were blinded to the pain results. The data presented normal distribution and ANOVA for repeated measures with 2 factors was used. There was no significant differences between groups (p>0,05) and all groups presented decreased pain levels after treatments. All the treatments were equally efficient in decrease pain related to CDH.

by Wai Ching Wa, Gina. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1990. / Bibliography: leaves 303-314. / Chapter 1. --- INTRODUCTION --- p.1 / Chapter 2. --- LITERATURE REVIEW ON CERVIX UTERI / Chapter 2.1 --- HISTOLOGY OF CERVIX UTERI --- p.4 / Chapter 2.2 --- CYTOLOGY OF CERVIX UTERI --- p.5 / Chapter 2.3 --- CERVICAL EPITHELIAL LESIONS / Chapter 2.3.1 --- Squamous Metaplasia --- p.7 / Chapter 2.3.2 --- Cervical Intraepithelial Neoplasia --- p.9 / Chapter 2.3.3 --- Viral Infections --- p.17 / Chapter 2.4 --- DIAGNOSTIC APPROACH TO CERVICAL LESIONS --- p.20 / Chapter 2.5 --- DIAGNOSTIC VARIABILITY OF CERVICAL LESIONS --- p.21 / Chapter 2.6 --- IMPORTANCE OF CERVICAL CARCINOMA IN HONG KONG --- p.21 / Chapter 3. --- LITERATURE REVIEW ON NASOPHARYNX / Chapter 3.1 --- HISTOLOGY OF NASOPHARYNX --- p.22 / Chapter 3.2 --- CYTOLOGY OF NASOPHARYNX --- p.24 / Chapter 3.3 --- NASOPHARYNGEAL EPITHELIAL LESIONS / Chapter 3.3.1 --- 'Squamous Metaplasia' --- p.25 / Chapter 3.3.2 --- Nasopharyngeal Intraepithelial Neoplasia --- p.26 / Chapter 3.3.3 --- Viral Infections --- p.27 / Chapter 3.4 --- DIAGNOSTIC APPROACH TO NASOPHARYNGEAL LESIONS --- p.28 / Chapter 3.5 --- IMPORTANCE OF NASOPHARYNGEAL CARCINOMA IN HONG KONG --- p.29 / Chapter 4. --- LITERATURE REVIEW ON MORPHOMETRY / Chapter 4.1 --- QUANTITATIVE ASSESSMENT OF CELL FEATURES --- p.30 / Chapter 4.2 --- TERMINOLOGY --- p.31 / Chapter 4.3 --- APPROACHES TO SAMPLING --- p.32 / Chapter 4.4 --- SOURCES OF VARIATION --- p.32 / Chapter 4.5 --- METHODOLOGY FOR MORPHOMETRY --- p.33 / Chapter 4.6 --- FEATURES FOR MORPHOMETRY IN INTRAEPITHELIAL NEOPLASIA --- p.35 / Chapter 4.7 --- PREVIOUS MORPHOMETRIC STUDIES ON INTRAEPITHELIAL NEOPLASIA --- p.36 / Chapter 5. --- MATERIALS AND METHODS / Chapter 5.1 --- MATERIALS / Chapter 5.1.1 --- Cervix Uteri --- p.41 / Chapter 5.1.2 --- Nasopharynx --- p.41 / Chapter 5.2 --- METHODS / Chapter 5.2.1 --- Equipment --- p.42 / Chapter 5.2.2 --- Pilot Study for Reproducibility --- p.43 / Chapter 5.2.3 --- Estimation of Minimum Sample Size --- p.43 / Chapter 5.2.4 --- Morphometric Procedures --- p.44 / Chapter 5.2.5 --- Statistical Analysis --- p.48 / Chapter 5.2.6 --- Comparison of Visual Diagnosis of Cervical smears and biopsies --- p.49 / Chapter 5.2.7 --- Survey of Subjective Assessment Criteria for Cervical Biopsies and Smears --- p.50 / Chapter 6. --- RESULTS / Chapter 6.1 --- PILOT STUDY / Chapter 6.1.1 --- Intraobserver Reproducibility --- p.52 / Chapter 6.1.2 --- Minimum Sample Size --- p.52 / Chapter 6.2 --- CERVIX / Chapter 6.2.1 --- Maturation Sequence of Cervical Epithelium --- p.53 / Chapter 6.2.2 --- Differences of Morphometric Means between various groups of Cervical Biopsies --- p.56 / Chapter 6.2.3 --- Discriminant Analysis of Cervical Biopsies --- p.58 / Chapter 6.2.4 --- Differences of Morphometric Means between various groups of Cervical Smears --- p.60 / Chapter 6.2.5 --- Discriminant Analysis of Cervical Smears --- p.61 / Chapter 6.2.6 --- Comparison of Cervical Smears and Biopsies --- p.62 / Chapter 6.2.7 --- Subjective Assessment Criteria for Cervical Biopsies and Smears --- p.63 / Chapter 6.3 --- NASOPHARYNX / Chapter 6.3.1 --- Maturation Sequence of Nasopharyngeal Epithelium --- p.65 / Chapter 6.3.2 --- Differences of Morphometric Means between various groups of Nasopharyngeal Biopsies --- p.68 / Chapter 6.3.3 --- Discriminant Analysis of Nasopharyngeal Biopsies --- p.70 / Chapter 6.4 --- COMPARISON OF CERVIX UTERI AND NASOPHARYNX --- p.71 / Chapter 7. --- DISCUSSION / Chapter 7.1 --- CERVIX UTERI / Chapter 7.1.1 --- Maturation Sequence --- p.73 / Chapter 7.1.2 --- Discrimination of different groups in Biopsies --- p.76 / Chapter 7.1.3 --- Discrimination of different groups in Smears --- p.77 / Chapter 7.1.4 --- Comparison of Smears and Biopsies --- p.78 / Chapter 7.1.5 --- Subjective Assessment Criteria --- p.80 / Chapter 7.1.6 --- Future directions --- p.81 / Chapter 7.2 --- NASOPHARYNX / Chapter 7.2.1 --- Maturation Sequence --- p.81 / Chapter 7.2.2 --- Discrimination of different groups --- p.84 / Chapter 7.2.3 --- Nasopharyngeal Cytology --- p.84 / Chapter 7.2.4 --- Future directions --- p.85 / Chapter 7.3. --- COMPARISON OF CERVIX UTERI AND NASOPHARYNX / Chapter 7.3.1 --- Morphometric data --- p.85 / Chapter 7.3.2 --- Discriminant Analysis --- p.87 / Chapter 8. --- CONCLUSIONS --- p.89 / Chapter APPENDIX A --- Survey of subjective assessment criteria for cervical biopsies and smears / Tables A1-A7 --- p.92 / Chapter APPENDIX B --- Results of pilot study / Tables B1-B6 --- p.100 / Chapter APPENDIX C --- Morphometric data and results of statistical tests for cervical biopsies / Fig. C1-C61 --- p.104 / Tables C1-C19 --- p.166 / Chapter APPENDIX D --- Morphometric data and results of statistical tests for cervical smears / Fig. D1-D2 6 --- p.179 / Tables D1-D3 --- p.206 / Chapter APPENDIX E --- Comparison of cervical smears and biopsies / Tables E1-E3 --- p.208 / Chapter APPENDIX F --- Morphometric data and results of statistical tests for nasopharyngeal biopsies / Fig. F1-F61 --- p.211 / Tables F1-F12 --- p.273 / Chapter APPENDIX G --- Comparison of nasopharyngeal and cervical biopsies / Tables G1-G15 --- p.282 / Chapter APPENDIX H --- Pictures of materials and equipment / Fig. H1-H21 --- p.291 / REFERENCES --- p.303

Orientador: Luis Otavio Zanatta Sarian / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-11-07T13:22:12Z (GMT). No. of bitstreams: 1 Oliveira_AntonioCarlosZulianide_D.pdf: 2312185 bytes, checksum: 6a45c1be8238c13c3a584fdc2ef426e4 (MD5) Previous issue date: 2013 / Resumo: Introdução: Ensaios clínicos das últimas duas décadas do século XX demonstraram a superioridade da radioterapia associada à quimioterapia na abordagem do carcinoma espinocelular do colo do útero (CEC). Contudo, tais estudos abordaram todos os estádios clínicos e para o subgrupo de mulheres com CEC estádio IIIB e os benefícios da quimioterapia não foram totalmente comprovados. Objetivos: Esta tese divide-se em dois estudos: 1) uma comparação histórica de sobrevida livre de doença (SLD), sobrevida total (ST) e toxicidade de tratamento em mulheres com CEC IIIB submetidas à braquiterapia de baixa taxa de dose (BBTD) versus braquiterapia de alta taxa de dose exclusiva (BATD) versus braquiterapia de alta taxa de dose associada à quimioterapia (BATD-QT) e 2) um ensaio clínico aleatorizado comparando esses mesmos parâmetros em mulheres submetidas à BATD versus BATD-QT. Métodos: Na comparação histórica de tratamentos, foram levantados os dados de evolução de pacientes admitidas entre 1985 e 2005 no CAISM-UNICAMP e seguidas até 2007, totalizando 230 pacientes com CEC IIIB que receberam BBTD (42 pacientes), BATD (155 pacientes) ou BATD-QT (33 pacientes). As SLD e ST das mulheres nos três grupos foram comparadas usando curvas de sobrevida tipo Kaplan-Meyer e testes de log-rank. Já o ensaio clínico aleatorizado foi realizado entre setembro de 2003 e julho de 2010. Foram incluídas no estudo 147 mulheres com CEC IIIB. Após aceitarem participar e assinarem o termo de consentimento, as mulheres foram randomizadas para BATD ou BATD-QT através de planilha de aleatorização criada pelo programa SAS e trazida ao conhecimento de pacientes e médicos através de envelopes opacos. Todas as mulheres receberam teleterapia com dose de 45Gy para a região pélvica em 25 frações, 14,4Gy de reforço no(s) paramétrio(s) comprometido(s) e BATD em quatro frações semanais de 7Gy, prescritos no ponto A. O grupo BATD-QT recebeu cisplatina concomitante semanal (40mg/m2) durante a teleterapia pélvica. O follow-up durou até janeiro de 2013, (72 pacientes do grupo com cisplatina e 75 no grupo-controle), com o seguimento médio de 54,9 meses (intervalo interquartil = 55,4 meses). Comparações de SLD e ST foram realizadas usando curvas de Kaplan-Meyer, testes de log-rank e modelos multivariados de Riscos Proporcionais de Cox, os quais englobaram características clínicas das mulheres como variáveis de controle. Resultados: Na comparação histórica, a SLD média para o grupo BATD foi de 60%, para BBTD 45% e para BATD-QT foi de 65% (p = 0,02). Já a ST foi de 65% para o grupo BATD, 49% para BBTD e a ST em dois anos para o grupo BATD-QT foi de 86% (p = 0,02). A toxicidade retal de grau II foi de 7% para o grupo que recebeu BBTD, de 4% para BATD e 7% para o grupo BATD-QT, que teve um caso de toxicidade retal grau IV. No ensaio clínico aleatorizado, mulheres alocadas no grupo BATD-QT tiveram SLD significativamente melhor (RR = 0,52, 95% CI 0,28-0,98, p = 0,04), porém não houve diferença em relação a ST (RR = 0,67, 95% CI 0,37-1,183, p = 0,16). Mulheres com Karnofsky <90 tiveram uma SLD significativamente pior (RR = 2,52, 95% CI 1,23-4,78, p = 0,01). O mesmo ocorreu para as mulheres com invasão parametrial bilateral até a parede óssea (RR = 2,93, 95% CI 1,21-7,13, p = 0,02), e a hemoglobina média durante o tratamento <10mg/dL (RR = 2,22, 95% CI 1,01-4,93, p = 0,04). A ST também foi menor em mulheres com Karnofsky <90 (RR = 2,75, 95% CI 1,29-5,87, p <0,01), e hemoglobina média durante o tratamento <10mg/dL (RR = 2,82, 95% CI 1,27-6,29, p = 0,01). Conclusões: Na revisão da série histórica, as pacientes que receberam braquiterapia de alta taxa de dose tiveram melhores SLD e ST, e as taxas de toxicidade não foram diferentes entre os três grupos. O ensaio clínico, que é o único estudo controlado randomizado comparando a BATD-QT e BATD para CEC IIIB, sugere que há um pequeno, mas significativo, benefício na SLD com a adição de cisplatina à BATD, com uma toxicidade aceitável / Abstract: Introduction: Clinical trials of the last two decades of the twentieth century demonstrated the superiority of radiotherapy combined with chemotherapy in the management of squamous cell carcinoma of the cervix (SCC). However, such studies have addressed all clinical stages and for the subgroup of women with stage IIIB SCC the benefits of chemotherapy have not been fully proven. Objectives: This thesis is divided into two studies: 1) a historical comparison of disease-free survival (DFS), overall survival (OS) and toxicity of treatment in women with SCC IIIB undergoing low-dose rate brachytherapy (LDR) brachytherapy versus high dose rate exclusive (HDR) brachytherapy versus high dose rate associated with chemotherapy (CHT) and 2) a randomized clinical trial comparing these parameters in women undergoing HDR versus CHT. Methods: In the historical comparison of treatments, data on the outcomes of patients admitted between 1985 and 2005 in CAISM-Unicamp and followed until 2007 were collected, totaling 230 patients with SCC stage IIIB who received either LDR (42 patients), HDR (155 patients) or CHT (33 patients). The DFS and OS of women in the three groups were compared using Kaplan-Meyer survival curves and the "log-rank" test. The randomized clinical trial was conducted between September 2003 and July 2010. A total of 147 with SCC stage IIIB were included. After accepting to participate and signing the consent form, women were randomized to HDR or CHT through a randomization spreadsheet created by SAS program and concealment allocation of patients through opaque envelopes. Patients of either the CHT or HDR groups received external-beam radiation (45 Gy) to the entire pelvic region in 25 fractions over a 5-week period. Compromised parametria were treated with 14.4 Gy boost. High-dose rate brachytherapy consisted of four weekly fractions of 7 Gy prescribed to point A. Patients in the CHT group also received concomitant weekly cisplatin (40mg/m2) during the pelvic external beam radiotherapy. The follow-up lasted until January 2013 (72 patients in the cisplatin group and 75 in the control group), with a mean follow-up of 54.9 months (interquartile range = 55.4 months). Comparisons of DFS and OS were performed using Kaplan-Meyer log-rank tests and multivariate models of Cox proportional hazards model, which encompassed the clinical characteristics of women as control variables. Results: In the historical comparison, the DFS for the group HDR was 60% , 45% for LDR and 65% for CHT (p = 0.02). The OS was 65% for the HDR group, 49% for LDR and 86% for CHT (p = 0.02). The Grade II rectal toxicity was 7% for LDR, 4% in HDR patients and 7% in CHT group, which had a case of rectal toxicity grade IV. In the randomized clinical trial, women in the CHT group had significantly better DFS (RR = 0.52, 95% CI from 0.28 to 0.98, p = 0.04), but there was no difference in OS (RR = 0.67, 95% CI 0.37 to 1.183, p = 0.16). Women with Karnofsky <90 had a significantly worse DFS (RR = 2.52, 95% CI 1.23 to 4.78, p = 0.01). The same was true for women with bilateral parametrial invasion to the bone wall (RR = 2.93, 95% CI 1.21 to 7.13, p = 0.02), and mean hemoglobin during treatment <10mg/dL (RR = 2.22, 95% CI 1.01 to 4.93, p = 0.04). The OS was also lower in women with Karnofsky <90 (RR = 2.75, 95% CI 1.29 to 5.87, p <0.01), and mean hemoglobin during treatment <10mg/dL (RR = 2, 82, 95% CI 1.27 to 6.29, p = 0.01). Conclusions: Patients who received HDR had better DFS and OS, and toxicity rates were not different among the three groups. The randomized trial, which is the only randomized controlled study comparing HDR and CHT for CEC IIIB, suggests that there is a small but significant DFS benefit with the addition of cisplatin to HDR, with acceptable toxicity / Doutorado / Oncologia Ginecológica e Mamária / Doutor em Ciências da Saúde

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A ideia de seguimento, na perspectiva de acompanhar de mulheres com diagnÃstico de CÃncer de Colo Uterino (CCU), identificar como estÃo sendo encaminhadas e tratadas no Sistema Ãnico de SaÃde (SUS), possibilita conhecer variÃveis, eventos e condiÃÃes que proporcionam uma avaliaÃÃo dessa Ãrea do cuidado e do sistema. à elevado o nÃmero de casos de CCU, que apesar de prevenÃveis e controlÃveis com os conhecimentos e as tecnologias existentes, apresenta taxas de morbidade e de mortalidade elevadas, sendo os aspectos associados ao acesso e à qualidade do seguimento fatores estreitamente relacionados a esse desfecho. Diante do exposto, o trabalho objetivou avaliar o seguimento de mulheres com CCU na perspectiva dos sistemas de informaÃÃo de saÃde e de mulheres que nÃo obtiveram registros de seguimento nestes sistemas. Trata-se de pesquisa documental, avaliativa e de campo, realizada em quatro etapas: listagem nominal de mulheres com diagnÃstico de CCU, residentes em Fortaleza-CE, registradas em 2008 no SISCOLO de Fortaleza; busca nominal de mulheres com diagnÃstico de CCU nas APAC-Onco, AIH e DeclaraÃÃo de Ãbito (DO); busca nominal de mulheres com diagnÃstico de CCU no prontuÃrio eletrÃnico das pacientes; e realizaÃÃo das entrevistas com mulheres nÃo identificadas na 2 e 3 etapas. As entrevistas foram realizadas por meio de visita domiciliÃria, de setembro a dezembro de 2010. Os resultados evidenciaram 80 casos de mulheres com diagnÃstico de CCU, residentes em Fortaleza-CE, em 2008. Destas, 2,6% encontravam-se abaixo de 25 anos, 61,2% na faixa de 25 a 59 anos e 36,2% apresentaram idade acima de 60 anos. O carcinoma epidermÃide invasivo acometeu 81,2% das mulheres, enquanto que o adenocarcinoma apresentou-se em 18,2% dos casos. A anÃlise nos sistemas de informaÃÃo SIA/SUS, SIH/SUS e SIM identificou procedimentos que caracterizaram seguimento de mulheres com diagnÃstico de CCU, em 50% das mulheres diagnosticadas. Da outra metade, 16,2% obtiveram seguimento identificado no prontuÃrio eletrÃnico; 33,7% nÃo apresentaram informaÃÃes de seguimento em nenhuma das fontes citadas, tendo estas sido selecionadas para entrevista. No entanto, destas, apenas 20% foram entrevistas, pois as demais nÃo ofereciam informaÃÃes suficientes para o acesso à pesquisadora. As entrevistas revelaram baixas condiÃÃes socioeconÃmicas destas mulheres. Os resultados de Papanicolaou foram entregues com cerca de um mÃs e na data agendada. Na identificaÃÃo de aspectos relacionados ao encaminhamento da paciente com CCU para outros nÃveis de referÃncia, 87,5% recebeu encaminhamento para algum tipo de instituiÃÃo com nÃvel de complexidade mais alto; quanto ao estado atual de seguimento, das mulheres entrevistadas, apesar da maioria ter realizado procedimentos que caracterizaram seguimento, ainda foi evidente a necessidade da educaÃÃo permanente para a qualificaÃÃo profissional, a fim de evitar iniquidades no atendimento à mulher acometida pelo CCU. Houve evidÃncia de subregistro no SIH. Confirmou-se a tese de que as informaÃÃes de seguimento das mulheres com CCU, em Fortaleza-CE, nÃo refletem a real magnitude de seguimento das mulheres que obtiveram diagnÃstico de CCU, uma vez que se constatou o acesso destas à realizaÃÃo dos procedimentos necessÃrios para o seguimento adequado.

Esta tese se fundamenta na necessidade de novos tratamentos para o câncer do colo de útero visando o aumento da adesão dos pacientes aos tratamentos, assim como à qualidade de vida dos mesmos. Nesse sentido, formulações nanotecnológicas foram desenvolvidas com o objetivo de carrear o fármaco imiquimode para um local específico – a mucosa vaginal – esperando gerar melhores desempenhos nesse tratamento quando comparados com a formulação comercial. Três nanoestruturas com morfologias distintas foram propostas visando potencializar o efeito do fármaco em células de câncer cervical (SiHa). As formulações desenvolvidas compreenderam: nanoemulsões (NEimiq), nanocápsulas poliméricas (NCimiq) e nanocápsulas poliméricas revestidas com quitosana (NCimiq-chit). Observou-se que nanocápsulas poliméricas produzidas com poli(ε-caprolactona) apresentaram efeito mais pronunciado frente às células SiHa. Para tanto, essas formulações (NCimiq e NCimiq-chit) foram incorporadas em hidrogéis de quitosana e de hidroxietilcelulose a fim de possibilitar uma melhor futura aplicação para o paciente. Estudos envolvendo mucosa vaginal suína demonstraram que ambas as formulações são mucoadesivas e permeiam a mucosa vaginal. Porém, a formulação produzida com hidrogel de quitosana (NCimiq) apresentou maior desempenho. Esta foi a formulação escolhida para dar continuidade aos estudos deste trabalho, sendo objeto de estudo posterior em cultura de células SiHa a fim de elucidar o mecanismo de ação da mesma. Esses estudos demonstraram que há uma ocorrência de processos combinados de diminuição da viabilidade celular de maneira tempo-dependente e que mecanismos como apoptose, autofagia e parada de ciclo celular estão presentes. Essa formulação (NCimiq) apresentou porcentagens de morte celular significativas, mesmo utilizando baixas concentrações do fármaco. Portanto, os achados desta tese constataram que nanoestruturas modulam efetivamente a interação do fármaco com as células. / This thesis deals with the need of new treatments for cervical cancer in order to increase the adherence of patients to the treatment as well as to improve their quality of life. In this sense, nanotechnological formulations were developed to carry imiquimod to a specific site – the vaginal mucosa – expecting to obtain better performance than the commercial drug in the cervical cancer treatment. Three nanostructures with different morphologies were proposed to potentilize the drug effect on cervical cancer cells (SiHa). The developed formulations are: nanoemulsions (NEimiq), polymeric nanocapsules (NCimiq) and polymeric nanocapsules coated with chitosan (NCimiq-chit). It was observed that polymeric nanocapsules produced with poly(ε-caprolactone) presented a stronger effect against SiHa cells. Therefore, formulations NCimiq and NCimiq-chit were incorporated into hydrogels of chitosan and hydroxyethylcellulose to enable a better future application on patients. The studies of this thesis involving porcine vaginal mucosa demonstrated that both formulations are mucoadhesive and that they provided a good drug permeation. However, the formulation produced with chitosan hydrogel (NCimiq) showed a better performance. This formulation was therefore chosen to follow the next steps of this work, conducted in SiHa cell culture to elucidate its action mechanism. This study demonstrated that there is an occurrence of combined processes of decreasing cell viability in a time-dependent type. The study also showed that mechanisms such as apoptosis, autophagy and cell cycle arrest are simultaneously present. The formulation NCimiq presented a significantly percentage of cellular death, even when low concentrations of the drug were used. Consequently, the findings of this thesis indicate that nanostructures effectively modulate the interaction of the drug with the cancer cells.

MPH, University of the Witwatersrand, Faculty of Health Sciences / Introduction Sex workers are considered to be a high risk group in the acquisition and transmission of sexually transmitted infections which include Human Immunodeficiency Virus (HIV) and Human Papillomavirus (HPV). Infection with HPV has been clearly established as a causative agent that infects the cells of the cervix and slowly causes cellular changes (dysplasia) or abnormal cells that can later develop into cancer. Women who are HIV positive are thought to be at higher risk of having HPV infection, and subsequently also at higher risk of having abnormal cervical lesions. Objectives The main focus of this study is to describe the prevalence of abnormal Pap-smears among sex workers and to further identify the difference between Pap-smear results of sex workers who are HIV-positive and HIV negative. Methods This is a retrospective descriptive study, where data was obtained from sex workers records from January 2004 to December 2006. The study population included all sex workers who attended the Esselen Street Clinic and sex worker outreach clinic in Hillbrow, in the inner-city of Johannesburg. Three hundred and nine records were randomly selected, of which 200 met the inclusion criteria. Data was collected on socio-demographic information including the age and place of residence, laboratory results (Pap-smear and HIV) and history of sexually transmitted infection at the last physical examination. Extracted data was captured in excel spreadsheet and transferred to Stata Computer Package software version 9.0 for data management and analysis. Descriptive analysis included frequency distributions of categorical variables (e.g. residence, Pap-smear results, HIV status and age group) and summary statistics of continuous variables (e.g. age). Pearson chi-square test or Fisher Exact test when necessary, where conducted to obtain proportions of the sex workers with abnormal Pap-smear results corresponding to each category of the explanatory variables for example age, HIV status and place of residence or business or business transactions. For continuous explanatory variables, such as age, two sample t-tests were used to determine differences between sex workers in terms of abnormal and normal Pap-smears. In all statistical considerations, a probability level of ≤0.05 was used. Results There were 200 records which were analysed to achieve the study objectives. These included 146 records of HIV positive (73%) and 54 of HIV negative sex workers (27%). Their ages ranged from 18 to 45 years with a mean of 26.85 years and median of 26.0 years. More than 70% (n=141) of the sex workers were below the age of 30 years. More than two thirds of sex workers lived in hotels and almost 90% was considered to be symptomatic for STIs. Eighty-eight (44%) of the sex workers were found to have had an abnormal smear result, of whom 58 (65.9%) were below the age of 30 years. Age, as a continuous variable, and place of residence (living on the street) was found to be statistically significantly associated with having an abnormal smear result. However, age (being older than 30), having symptoms of an STI and being HIV positive was not found to be statistically significantly associated with having an abnormal Pap-smear result. Conclusion This study has shown that the prevalence of abnormal Pap-smears among Hillbrow sex workers was high, especially in young sex workers. Sex workers who operated from the street were found to have a higher percentage of abnormal smear results as compared to those operating from the brothels and flats, signifying a need for a controlled environment and to improve sex workers access to health care services. No significant association was found between HIV status and abnormal Pap-smears. Further studies are required in this area. The study indicates that they may be a need to review the National Cervical Cancer Screening Policy to take into consideration the needs of high risk population, such as sex workers.

La Bolivie a des taux d’incidence et de mortalité associés au cancer du col de l’utérus qui setrouvent parmi les plus élevés de l’Amérique. Le programme national de prévention du cancerdu col de l’utérus est basé sur le test Papanicolaou et l’inspection visuelle avec acide acétiquepour la détection de lésions précancéreuses. Cependant, divers types de barrières (économique,socio-culturelle et géographique) empêchent que ce programme ne parvienne à réduireefficacement l’incidence du cancer du col de l’utérus en Bolivie.Le principal facteur étiologique associé au développement du cancer du col de l’utérus estl’infection persistante par les papillomavirus humains à haut-risque (HPV-HR). L’introductionde tests qui permettent la détection du matériel génétique des HPV-HR a donc le potentiel deréduire l’incidence et la mortalité associées à ce cancer dans le monde. De plus, ce test peut êtreréalisé sur des échantillons auto-prélevés. Ceci permettrait une augmentation du taux departicipation des femmes dans les programmes de dépistage primaire.Dans ce travail de thèse, nous proposons une stratégie de faible coût pour la détection des HPVHR.Cette stratégie commence par l’auto-prélèvement de cellules cervico-vaginales avec uncoton-tige et le transport des échantillons à sec sur une lame de verre. Ensuite, l’ADN estrécupéré avec un protocole simple utilisant la résine Chelex-100 et la protéinase K. Un contrôlede qualité de l’extraction d’ADN est réalisé avec une PCR amplifiant un fragment du gène dela b-globine humaine. Finalement, la détection des HPV-HR est faite avec une combinaison dedeux techniques :PCR BSGP-EIA et PCR pU. Toutes les étapes de cette stratégie ont été validéanalytiquement en utilisant des dispositifs et techniques standards comme référence. Dans cetravail nous montrons aussi le bon degré d’acceptabilité envers l’auto-prélèvement par lapopulation féminine locale de Cochabamba. Les différentes études ont été réalisées dans ledépartement de Cochabamba entre août 2014 et mai 2018.Notre stratégie a le potentiel d’améliorer le programme de dépistage du cancer du col de l’utérusen Bolivie étant donné que les femmes préfèrent faire un auto-prélèvement et que nostechniques sont plus sensibles analytiquement pour la détection des HPV-HR. Cependant, il estimpératif que le système de santé public bolivien améliore le suivi clinique des femmes à risqueafin de réduire efficacement l’incidence et la mortalité provoquées par le cancer du col del’utérus. / Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie) / info:eu-repo/semantics/nonPublished