Alzheimer's disease (AD) is significantly more prevalent among African Americans than within the general population, but rates of early detection are lower in the African American community. Researchers have demonstrated that both pessimistic Alzheimer's-directed health beliefs, and negative perceptions of the effectiveness and the accessibility of medical care act as barriers to care seeking by African American family members of individuals with the disease. Recent research into causal judgments made by potential caregivers about individuals with undiagnosed AD suggests that gender bias and errors in attribution may constitute covert barriers to both lay and professional interpretations regarding the need for cognitive assessment. This study used grounded theory to investigate whether African American family caregivers hold integrated, gender-distinct beliefs about causal attributions of their family member's cognitive decline which may contribute to a delay in care-seeking behaviors. The health belief model was used in conjunction with the attribution theory as the conceptual framework for understanding the data. Purposive sampling of geriatric and memory clinics, and a church was used to recruit eight family caregivers who participated in in-depth interviews. The results indicated that there is a significant lack of caregivers' knowledge and understanding of AD regardless of gender, and that this lack is linked to delays in diagnosis. These results may be used to support the development of a new theory of family caregivers' knowledge and understanding of AD. The social change implications include decreasing delayed diagnosis through increased educational awareness, community outreach programs, and universal mandatory cognitive testing of AD for at-risk individuals.

L’objectif de cette thèse était d’étudier la distribution, les déterminants et les conséquences des délais diagnostiques des cancers de l’enfant, par une revue systématique de la littérature, une analyse des plaintes déposées en France et au Canada et par des études ad hoc en population sur les tumeurs ayant des délais particulièrement longs : le médulloblastome et le sarcome d’Ewing.La revue systématique n’a pas retrouvé de diminution significative de la longueur des délais au cours du temps. Les délais longs étaient associés à un âge élevé, au type histologique et à la localisation de la tumeur. Les relations entre délai et gravité de la maladie étaient variables. Seul un tiers des conclusions des expertises judiciaires (n = 56) étaient concordantes avec les données de la littérature.Le délai diagnostique médian des enfants atteints de médulloblastome en Ile-de-France (n = 166) était de 65 jours. Les délais longs étaient associés paradoxalement à des métastases moins fréquentes et à une histologie favorable, mais pas à la survie ni aux séquelles.Le délai diagnostique médian des enfants atteints de sarcome d’Ewing en France (n = 436) était de 70 jours. Les délais longs, liés à un âge élevé et à la localisation de la tumeur, n’étaient pas associés au volume tumoral, à la présence de métastases, à l’opérabilité ni à la survie.Pour certaines tumeurs, une association entre délais diagnostiques et gravité est établie (rétinoblastome) ou hautement probable. Pour d’autres, l’absence d’association démontrée permettrait de dédramatiser la perception de leurs conséquences, sans dispenser d’essayer de réduire ces délais, notamment pour en atténuer les conséquences psychologiques. / The aim of this thesis was to study the distribution, determinants and consequences of time to diagnosis of cancer in children, through a systematic review of the literature and an analysis of lawsuits in France and Canada, and two population-based studies of tumors with particularly long diagnosis delays: medulloblastoma and Ewing sarcoma.The systematic review did not identify any significant decreases in time to diagnosis during the studies. Long times to diagnosis were associated with older age, histological type and location of the tumor. Associations between time to diagnosis and severity of the disease varied. Only a third of the court-appointed experts (n = 56) provided testimony concordant with the available medical literature.The median time to diagnosis of children with medulloblastoma in the area of Paris (n = 166) was 65 days. Diagnosis delays were paradoxically associated with less frequent metastasis and favorable histology, but not with survival, or sequelae.The median time to diagnosis of children with Ewing sarcoma in France (n = 436) was 70 days. Diagnosis delays, related with older age and tumor location, were not associated with tumor size, presence of metastasis, surgical outcome, or survival.For some tumors, an association between time to diagnosis and severity of the disease is well established (e.g. retinoblastoma), or highly probable. For others, the lack of demonstrated associations could tone down the perception of the supposed consequences of diagnosis delays - but does not exempt from trying to reduce them, in order to alleviate their psychological consequences.

<p>Napredak na polju molekularne biologije omogućio je identifikaciju molekularnih markera za karcinom bronha sa vrednim prognostičkim i prediktivnim značajem i njihova uloga kod uznapredovalog, metastatskog oblika bolesti je u velikoj meri istražena, dok kod ranih stadijuma bolesti jo&scaron; uvek nije sasvim jasna. Cilj ovog istraživnja bio je da se utvrdi učestalost najče&scaron;ćih genskih alteracija u tumorskim ćelijama bolesnika sa ranim stadijumom adenokarcinoma bronha, da se utvrdi pojedinačna zavisnost ispitivanih genskih alteracija u tumorskim ćelijama sa određenim kliničko-patolo&scaron;kim karakteristikama i da se utvrdi potencijalni prognostički značaj pojedinačne genske alteracije u tumorskim ćelijama na vreme preživljavanja bez povratka bolesti i ukupno vreme preživljavanja. Istraživanje je obuhvatilo 161 bolesnika sa adenokarcinomom bronha, stadijuma bolesti od I do IIIA, kod kojih je sprovedena radikalna hirur&scaron;ka resekcija u Institutu za plućne bolesti Vojvodine u periodu izmedju 2007 i 2014 godine. U tumorskim uzorcima fiksiranim u parafinu odredjivane su mutacije EGFR, KRAS i PIK3CA gena, ALK i ROS1 rearanžman i PD1 i PD-L1 ekspresija. Kliničkopatolo&scaron;ke karakteristike su preuzete iz registra za karcinom bronha Instituta za plućne bolesti Vojvodine. Ukupno preživljavanje je računato od dana operacije do dana smrti, a preživljavanje bez povratka bolesti je računato od dana operacije do momenta ponovne pojave bolesti. Od 161 testiranog tumorskog uzorka, prisustvo mutacija detektovano je kod 96 uzoraka (59.6%). Prisustvo mutacije KRAS gena detektovano je kod 69 (42.9%), mutacije EGFR gena kod 10 (6.2%), a mutacije PIK3CA gena kod 7 (4.3%) tumorskih uzoraka. ALK rearanžman je detektovan kod 3 (1.9%), a ROS1 rearanžman kod 7 (4.3%) tumorskih uzoraka. PD-1 ekspresija detektovana je u 71 tumorskom uzorku (45%), dok je PD-L1 ekspresija detektovana u 59 tumorskih uzoraka (36.6%). PD-1 ekspresija nije bila značajno povezana ni sa jednim od klinčko-patolo&scaron;kih karakteristika (uključujući KRAS, EGFR, ALK, ROS1 i PI3KCA status). PD-L1 ekspresija je bila značajno povezana sa tipom hirurgije (P = 0.01) i sa prisustvom KRAS mutacije (P = 0.02). Mutacioni status u domenu KRAS gena je bio značajno povezan sa godinama starosti (P = 0.004), polom (P = 0.006) i pu&scaron;ačkim statusom (P = 0.004). Mutacioni status u domenu EGFR gena je bio značajno povezan sa pu&scaron;enjem (P &lt; 0.001) i sa godinama starosti (P = 0.013). Mutacioni statusi u domenu gena za ALK, ROS1 i PI3KCA nisu bili značajno povezani ni sa jednom od ispitivanih kliničko-patolo&scaron;kih karakteristika. Prisustvo PD-1 ekspresije je bilo značajno povezano sa preživljavanjem bez povratka bolesti (P = 0.03) i ukupnim preživljavanjem (P = 0.01). PD-L1 ekspresija, KRAS, EGFR, ALK, ROS1 i PIK3CA mutacioni status nisu bili značajno opvezani sa preživljavanjem bez povratka bolesti i ukupnim preživljavanjem. Najče&scaron;će detektovane genske alteracije su mutacije u domenu KRAS i EGFR gena. Prisustvo KRAS mutacije je značajno povezano sa godinama starosti ispitanika, polom i pu&scaron;ačkim statusom dok je prisustvo EGFR mutacije značajno povezano sa godinama starosti ispitanika i pu&scaron;ačkim statusom. Prisustvo PD-L1 ekspresije je značajno povezano sa vrstom hirur&scaron;kog lečenja i sa prisustvom KRAS mutacija. Jedino prisustvo PD-1 ekspresije u tumorskim ćelijama predstavlja nezavistan prognostički faktor za preživljavanje bez povratka bolesti i ukupno preživljavanje bolesnika sa ranim stadijumom adenokarcinoma bronha.</p> / <p>Advances in the field of molecular biology gave us insight into biomarkers for lung cancer with great prognostic and predictive value and their role in advanced stage disease is well known while in early stage disease is yet to be proven. The aim of this study was to determine the frequencies of the most common gene alterations in patients with early stage lung adenocarcinoma, to determine the relationship between gene alterations in tumor cells and clinicopathologial characteristics and to determine prognostic value of each gene alteration regarding overall survival and disease free survival. One hundred sixty-one patients diagnosed with lung adenocarcinoma clinical stage I-IIIA who underwent radical surgical resection at the Institute for Pulmonary Diseases of Vojvodina between 2007 and 2014 were included in this study. Mutations in EGFR, KRAS and PIK3CA gene, ALK and ROS1 rearrangement and PD-1 and PD-L1 expression were determined in representative formalin-fixed, paraffin-embedded (FFPE) tumor block from each patient. Clinical data were extracted from the institutional lung cancer registry of the Institute for Pulmonary Diseases. Overall survival was calculated as time from the day of surgery to the day of death. Disease free survival was calculated as time from the day of surgery to the day of disease relapse. Among 161 tested tumor tissue, presence of mutation was found in 96 (59.6%) of them. There were 69 (42.9%) mutations in KRAS gene, 10 (6.2%) in EGFR gene and 7 (4.3%) in PIK3CA gene. ALK and ROS1 rearrangement were present in 3 (1.9%) and 7 (4.3%), respectively. PD-1 expression was determined in 71 (45.0%) tumor sample while PD-L1 expression was determined in 59 (36.6%). PD-1 expression was not correlated with any of the clinicopathologial characteristics (including KRAS, EGFR, ALK, ROS1 and PIK3CA mutational status). PD-L1 expression correlated with type of surgery (P = 0.01) and KRAS positivity (P = 0.02). KRAS mutation status correlated with age (P = 0.004), sex (P = 0.006) and smoking status (P = 0.004). EGFR status correlated with smoking status (P &lt; 0.001) and age (P = 0.013). ALK, ROS1 and PIK3CA status were not correlated with any of the clinicopathologial characteristics. PD-1expression was significantly associated with disease free survival (P = 0.03) and overall survival (P = 0.01). PD-L1 expression, KRAS, EGFR, ALK, ROS1 and PIK3CA status were not associated with disease free survival and overall survival. The most frequent gene alteration are mutations in KRAS and EGFR gene. Presence of KRAS mutation is in correlation with patients age, sex and smoking status while presence of EGFR mutation is in correlation with patients age and smoking status. PD-L1 expression is in correlation with type of surgery and KRAS mutational status. Only presence of PD-1 expression represent an independent prognostic factor for disease free survival and overall survival.</p>

No description available.

Submitted by Gilvan Almeida (gilvan.almeida@icict.fiocruz.br) on 2016-09-26T14:06:06Z No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 143.pdf: 1481528 bytes, checksum: b79a3d07ca080b52481916d2023f25b5 (MD5) / Approved for entry into archive by Barata Manoel (msbarata@coc.fiocruz.br) on 2016-10-20T13:18:24Z (GMT) No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 143.pdf: 1481528 bytes, checksum: b79a3d07ca080b52481916d2023f25b5 (MD5) / Made available in DSpace on 2016-10-20T13:18:24Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 143.pdf: 1481528 bytes, checksum: b79a3d07ca080b52481916d2023f25b5 (MD5) Previous issue date: 2012 / Fundação Oswaldo Cruz. Casa de Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. / Este estudo trata das ações médicas para prevenção do câncer do colo do útero no Brasil durante o período de 1936 a 1970. O câncer do colo do útero foi incorporado à agenda médica brasileira na década de 1940, a partir do desenvolvimento de ferramentas de diagnóstico precoce e da organização de instituições. Nosso objetivo neste trabalho é analisar o processo de incorporação da doença na medicina brasileira, impulsionado pela introdução e difusão das tecnologias de diagnóstico, no escopo de institucionalização da cancerologia como sub campo da nossa medicina. O Instituto de Ginecologia (IG), no Rio de Janeiro, sob chefia do médico Arnaldo de Moraes, foi o centro de difusão e ensino da colposcopia e da citologia no Brasil. Nossa hipótese de pesquisa é que a colposcopia foi a impulsionadora da formação e organização das instituições de controle do câncer do colodo útero no Brasil em meados do século XX, sendo utilizada de forma conjunta com a citologia até os anos 1960. A organização de ações sobre a doença e as discussões entre os especialistas conduziram à formação de uma rede de prevenção, construída a partir de publicações especializadas, associações profissionais, iniciativas para formação de pessoal e intercâmbio científico. Fizeram parte desta rede o Instituto de Ginecologia, o Hospital de Ginecologia da Faculdade de Medicina de Minas Gerais e o Hospital Aristides Maltez na Bahia. Ambos, com suas peculiaridades, se constituíram como espaços de controle da doença em suas regiões e de institucionalização de um modelo específico de ação que se afirmou no país até a década de 1970. / This study is about the medical actions for cervical cancer prevention in Brasil, from 1936 to 1970. Cervical cancer was incorporated into the medical Brazilian agenda in the 1940s, with the development of early detection tools and the institutions organization. Our objective in this paper is to analyze the disease incorporation on the Brazilian medicine, through the introduction and diffusion of diagnosis technologies, in the scope of cancerology institutionalization as a medicine sub field. The Instituto de Ginecologia (IG), in Rio de Janeiro, under leadership of physician Arnaldo de Moraes, was the learning and dissemination center of colposcopy and cytology in Brazil. Our research hypothesis is that colposcopy was the promoter of the formation and organization of the institutions to cervical cancer control in Brazil in the mid-twentieth century, being used, at the same time, with cytology until the 1960s. The organization of actions about the disease and the discussions among experts led to the formation of a prevention network that was constructed by specialized publications, professional associations, initiatives for personnel training and scientific exchange. The Instituto de Ginecologia, the Hospital de Ginecologia of Minas Gerais and the Hospital Aristides Maltez in Bahia were part of this network. All of them, with their peculiarities, had been constituted as spaces to disease control in their regions and institutionalization of a particular model of action, that was affirmed in the country until the 1970s.

Many older adults desire to maintain their quality of life by living and aging independently in their own homes. However, it is difficult for older adults to notice and track the subtle changes in their own abilities because these abilities can change gradually over a long period of time. Technology in the form of ubiquitous sensors embedded in objects in the home can play a role in keeping track of the functional abilities of individuals unobtrusively, objectively, and continuously over a long period of time. This work introduces a sensing technique called “task-based embedded assessment” that monitors how well specific tasks important for independence are carried out using everyday objects found in the home with which individuals regularly interact. Following formative studies on the information needs of older adults and their caregivers, a sensing system called “dwellSense” that can monitor, assess, and provide feedback about how well individuals complete tasks, such as taking medications, using the phone, and making coffee, was designed, built, and evaluated. Multiple longterm (over 10 months) field deployments of dwellSense were used to investigate how the data collected from the system could support greater self-awareness of abilities and intentions to improve in task performance. Presenting and reflecting on data from ubiquitous sensing systems such as dwellSense is challenging because it is both highly dimensional as well as large in volume, particularly if it is collected over a long period of time. Thus, this work also investigates the time dimension of reflection and has identified that real-time feedback is particularly useful for supporting behavior change, and longer-term trended feedback is useful for greater awareness of abilities. Traditional forms of assessing the functional abilities of individuals tend to be either biased, lacking ecological validity, infrequent, or expensive to conduct. An automated sensor-based approach for assessment is compared to traditional performance testing by a trained clinician and found to match well with clinician-generated ratings that are objective, frequent, and ecologically valid. The contributions from this thesis not only advance the state of the art for maintaining quality of life and care for older adults, but also provide the foundations for designing personal sensing systems that aim to assess an individual’s abilities and support behaviors through the feedback of objective, timely sensed information.

This thesis addresses the three principal questions concerning the development of CT urography for investigating haematuria and each question is the subject of a separate chapter. The questions are: What is the reasoning behind using CT urography? What is the optimum diagnostic strategy using CT urography? What are the problems with using CT urography and how may solutions be provided? Haematuria can signify serious disease such as urinary tract stones, renal cell cancer, upper tract urothelial cancer (UTUC) and bladder cancer (BCa). CT urography is defined as contrast enhanced CT examination of kidneys, ureters and bladder. The technique used here includes unenhanced, nephrographic and excretory-phases for optimized diagnosis of stones, renal masses and urothelial cancer respectively. The reasoning behind using excretory-phase CT urography for investigating haematuria is based on results showing its high diagnostic accuracy for UTUC and BCa. Patients with haematuria are classified as low risk or high risk for UTUC and BCa, by a risk score, determined by the presence/absence of risk factors: age > 50 years, visible or nonvisible haematuria, history of smoking and occupational exposure. The optimum diagnostic strategy for patients at high risk for urothelial cancer, uses CT urography as a replacement test for ultrasonography and intravenous urography and as a triage test for flexible and rigid cystoscopy, resulting in earlier diagnosis and potentially improving prognosis. For patients at low risk, ultrasonography, unenhanced and nephrographic-phase CT urography are proposed as initial imaging tests. Problems with using CT urography include false positive results for UTUC, which are eliminated by retrograde ureteropyelography-guided biopsy, an innovative technique, for histopathological confirmation of diagnosis. Recommendations for the NHS and possible future developments are discussed. CT urography, including excretory-phase imaging, is recommended as the initial diagnostic imaging test before cystoscopy for patients with haematuria at high risk for urothelial cancer.