The purpose of this work was to develop novel optical imaging technology and algorithms as a nondestructive method for detection and diagnosis of cancer in breast specimens. There are many ways in which the diagnosis of disease can benefit from fast and intelligent optical imaging technology. Our existing ability to provide this diagnosis depends on time-consuming pathology analysis. Optical coherence tomography (OCT) is a non-invasive optical imaging modality that provides depth-resolved, high-resolution images of tissue microstructure in real-time. OCT could provide a rapid evaluation of specimens while patients are still in the office, and has strong potential to improve the efficiency in evaluation of breast pathology specimens (biopsy or surgical). In this work, we demonstrate an imaging system to address this unmet clinical need, artificial intelligence algorithms to interpret the images, and early work towards miniaturizing the technology. We present an OCT system that achieves a line scan rate of 250kHz, meaning we can image a pathology cassette in 41 seconds, which is more than double the fastest scan rate in the field. By utilizing a multiplexed superluminescent diode (SLD) light source, which has strong noise performance over imaging speed, we achieve high resolution imaging under 5 um in tissue (axially and laterally). The system features a 1.1 mm 6-dB sensitivity fall-off range when imaging at 250 kHz. The scanner features large-area scanning with the implementation of a 2-axis motorized stage, enabling visualization of areas up to 10 cm x 10 cm (prior work visualizes 3 mm x 3mm). We showcase the results of demonstrating the performance of this system on a 100-patient clinical imaging study of breast biopsies, as well as imaging of clinical pathology specimens from the breast, prostate, lung, and pancreas in an IRB-approved study. Further, we show our work towards developing artificial intelligence (AI) for cancer detection within OCT images. Using retrospective data, we developed a type of AI algorithm known as a convolutional neural network (CNN) to classify OCT images of breast tissue from 49 patients. The binary cancer classification achieved 94% accuracy, 96% sensitivity, and 92% specificity. This framework had higher accuracy than the 88% accuracy of 7 clinician readers combined in our lab’s earlier multi-reader study. Lastly, we demonstrate a supercontinuum light source based on a 1 mm2 Si3N4 photonic chip for OCT imaging that has better performance than the state-of-the-art laser. Existing broadband laser sources for OCT are large, bulky, and have high excess noise. Our Si3N4 chip fundamentally eliminates the excess noise common to lasers and achieves 105 dB sensitivity and 1.81 mm 6-dB sensitivity roll-off with only 300 µW power on the sample.

Decision support systems have emerged over five decades ago to serve decision makers in uncertain conditions and usually rapidly changing and unstructured problems. Most decision support approaches, such as Bayesian decision theory and computing with words, compare and analyze the consequences of different decision alternatives. Bayesian decision methods use probabilities to handle uncertainty and have been widely used in different areas for estimating, predicting, and offering decision supports. On the other hand, computing with words (CW) and approximate reasoning apply fuzzy set theory to deal with imprecise measurements and inexact information and are most concerned with propositions stated in natural language. The concept of a Z-number [69] has been recently introduced to represent propositions and their reliability in natural language. This work proposes a methodology that integrates Z-numbers and Bayesian decision theory to provide decision support when precise measurements and exact values of parameters and probabilities are not available. The relationships and computing methods required for such integration are derived and mathematically proved. The proposed hybrid methodology benefits from both approaches and combines them to model the expert knowledge and its certainty (reliability) in natural language and apply such model to provide decision support. To the best of our knowledge, so far there has been no other decision support methodology capable of using the reliability of propositions in natural language. In order to demonstrate the proof of concept, the proposed methodology has been applied to a realistic case study on breast cancer diagnosis and a daily life example of choosing means of transportation.

No description available.

Bakgrund: Tro är en kraftkälla och kan förknippas med framtidshopp. Tro kan ge tröst samt hjälpa individen att hantera rädsla och osäkerheten. Ett besked om en cancerdiagnos kan leda till kognitiva, beteendemässiga och emotionella påverkan hos patienten, därtill medföra olika andliga behov hos patienten, så som tillit, hopp, förlåtelse, att tro på något högre och ett meningsfullt liv. Om dessa behov tillgodoses kan det leda till minskad lidande för patienten. Syfte: Att beskriva patienters erfarenheter av trons betydelse vid svåra besked så som att få en cancerdiagnos. Metod: En litteraturstudie där åtta kvalitativa artiklar inkluderades. Artiklarna analyserades med en fem stegs analysmodell. Resultat: Patientupplevelser presenteras i fyra kategorier: En hjälp för att hantera sjukdomen, Relation med Gud, Andlighet och andlig omvårdnad och Cancersjukdomens positiva och negativa påverkan. Tio subkategorier framkom: Att hantera cancersjukdom, smärta och skrämmande upplevelser genom tillit på Gud, Patienternas existentiella dimensioner och deras upplevda rädsla, Patienternas sökande och behov av att hitta mening med livet, Det är Guds vilja att drabbas av sjukdom och att bli botad, Förändrad relation med Gud på grund av cancersjukdom, Relation med andra troende och patienternas upplevda effekt av religiösa texter, Patienternas upplevda effekt av andlighet, Upplevelser om otillfredsställande andlig vård vid omvårdnad, Den individuella upplevda påverkan av cancersjukdom och Cancersjukdomens påverkan på familjerelation och vänskap. Konklusion: Patienterna i denna litteraturstudie upplevde att tron var en kraftkälla för att hantera cancerdiagnos. Relation med Gud hade stor betydelse för patienter som drabbats av cancer. Det framkom även att andlighet underlättade för patienter att gå vidare med livet. Brist på tid och vårdmiljö visade sig vara ett hinder vid tillhandahållande av andlig vård. / Background: Faith is a source of strength and can be associated with hope for the future. Faith can provide comfort and help the individual deal with fear and uncertainty. A message about a cancer diagnosis can lead to cognitive, behavioral and emotional effects in the patient, in addition to this bringing about various spiritual needs in the patient, such as trust, hope, forgiveness, to believe in something higher and a meaningful life. If these needs are met, it can lead to reduced suffering for thepatient. Aim: To describe patients' experiences of the importance of faith in difficult news such as receiving a cancer diagnosis. Method: A literature study in which eight qualitative articles were included. The articles were analyzed using a five-step analysis model. Findings: Patient experiences are presented in four categories: A help to deal with the disease, Relationship with God, Spirituality and spiritual care and Cancer's positive and negative impact. Ten subcategories emerged: Dealing with cancer, pain and frightening experiences through trust in God, Patients' existential dimensions and their perceived fear, Patients' search and need to find meaning in life, It is God's will to suffer from illness and to become cured, Changed relationship with God due to cancer, Relationship with other believers and patients' perceived effect of religious texts, Patients' perceived effect of spirituality, Experiences of unsatisfactory spiritual care in nursing, The individual perceived impact of cancer and The impact of cancer on family relationships and friendships. Conclusion: The patients in this literature study felt that faith was a source of strength in dealing with a cancer diagnosis. Relationship with God was of great importance to patients affected by cancer. It also emerged that spirituality made it easier for patients to move on with life. Lack of time and care environment was found to be a barrier in the provision of spiritual care.

Real world data have enhanced healthcare research, improving our understanding of disease progression, aiding in diagnosis, and enabling the development of personalized and targeted treatments. In recent years, multi-omics data and electronic health record (EHR) data have become increasingly available, providing researchers with a wealth of information to analyze. The use of machine learning methods with EHR and multi-omics data has emerged as a promising approach to extract valuable insights from these complex data sources. This dissertation focuses on the development of supervised and unsupervised learning methods, as well as their applications to EHR and multi-omics data, with a particular emphasis on early detection of clinical outcomes and identification of novel cancer subtypes. The first part of the dissertation centers on developing a risk prediction tool using EHR data that enables disease early detection so that preventive treatments can be taken to better manage the disease. For this goal, we developed a similarity-based supervised learning method with two applications to predict end-stage kidney disease (ESKD) and aortic stenosis (AS). In the second part of the dissertation, we expanded our goal to a phenome-wide prediction task and developed a patient representation based deep learning method that is able to predict phenotypes across the phenome. Through a weighting scheme, this approach is conducting tailored disease phenotype prediction computationally efficiently with good prediction performance. In the final part of the dissertation, I shifted the focus with the goal to identify clinical meaningful novel disease subtypes with unsupervised learning methods using multi-omics data. We tackled this goal through integrating multiple patient graphs being generated from multiple omics data with molecular level features for an improved disease subtyping. This dissertation has significantly contributed to the development of data-driven approaches to healthcare and biomedical research using EHR data and multi-omics data. The new methodologies developed with applications in multiple diseases using EHR and multi-omics data advanced our knowledge in disease diagnosis, vulnerable groups identification, and ultimately improve patient care.

The glyceryl enol ether fecapentaene-12 (FP-12) is a direct-acting mutagen that is formed by bacteria in the lower part of the gastrointestinal tract from a precursor of unknown structure. Two major unsolved questions concerning FP-12 are the structure of its precursor and the nature of its interaction (if any) with DNA. The structure of the biosynthetic precursor of FP-12 is thought to be that of a plasmalogen with an intact pentaenyl ether moiety. A synthesis of the perhydro analog of the proposed precursor structure is described, and approaches to the synthesis of the precursor itself are also described. Comparison of chromatographic data for the saturated model precursor and natural precursor provided evidence for the structure of the latter. The nature of the interactions of FP-12 with DNA was probed by model studies of the reaction of nucleoside bases with FP-12 and two proposed FP-12 metabolites. No adducts were formed between FP-12 or between the various putative polyenal metabolites and guanosine, cytosine, or thymidine. A model epoxy ether did react with a guanosine derivative, however, indicating that an epoxy ether derivative of FP-12, if formed, would be capable of reacting with DNA. / Ph. D.

研究背景： / 2009年起，中國政府發起並資助了一項覆蓋全國31個省221個鄉村、針對100萬名農村婦女的細胞學及肉眼觀察宮頸癌篩查試點項目。國家及地方政府需要對可行的篩查策略進行衛生經濟學評估，為下一步擴大規模的篩查提供政策依據。 / 研究目標： / 應用人群特異性Markov模型，對巴氏塗片及肉眼觀察的宮頸癌篩查策略進行成本效果及成本效用兩方面的衛生經濟學評估，進而為中國農村婦女宮頸癌篩查政策的制定提供依據。 / 研究方法： / 本論文工作建立了Markov人群動態擬合模型，該模型能夠整合與中國農村宮頸癌流行情況相吻合的成本及健康狀況的數據，進而用於擬合20年內35-59歲中國農村婦女在有/無篩查幹預下的成本、效用和效果。本文分析的八個備選篩查策略包括：採用醋酸染色肉眼觀察（VIA）或傳統細胞學（巴氏塗片）分別進行10年，5年，3年及1年一次的篩查。 / 本文從社會學角度出發，成本數據涵蓋篩查、診斷及治療過程中產生的直接及間接成本。模型在結構上綜合了已被廣泛認可的宮頸癌自然發展史模型，以及宮頸癌及其癌前病變（CIN）在中國農村進行篩查和治療的標準臨床路徑。模型輸入參數盡可能地使用了能夠反映中國農村婦女人群特異性的數據。通過對比國家報告數據與模型預測結果，本文從全死因死亡率、宮頸癌死亡率及宮頸癌發病率三個方面驗證了模型的可信度。 / 模型的結局變量包括：累計成本、累計生命年(LYs)、累計質量調整生命年(QALYs)、預期宮頸癌死亡率及發病率降低百分比(%)、CIN 相對風險、宮頸浸潤癌相對風險，增量成本效用比(ICUR, 表述為每挽救一個質量調整生命年消耗的成本)及增量成本效果比(ICER, 表述為每挽救一個生命年消耗的成本)等。與無篩查幹預相比，我們界定ICUR及ICER小於三倍人均國內生產總值（76,824元，2009年)的優勢策略為‘具有成本效益’的選擇，並將其中ICUR和ICER最低的策略，定義為‘最具成本效益’的策略，將具有最大健康效益的策略（挽救最多質量調整生命年或生命年的策略），定義為‘最有效’的策略。同時，我們對可能影響決策的不確定因素進行了敏感性分析。 / 結果： / 與無篩查幹預相比，肉眼觀察及巴氏塗片篩查均能夠減少宮頸癌患病例數，進而顯示出一定的健康效益。較短的篩查間隔具有更高的健康效益。模型預測在不同的篩查策略幹預下，宮頸癌死亡率和發病率分別有望降低6.67-31.95%和5.12-24.71%，預期CIN發病相對風險為0.89-0.98，預期宮頸癌發病相對風險為0.73-0.95。篩查幹預對健康的保護作用在本研究中得到了證實。 / 成本效用分析顯示，10年一次的肉眼觀察策略最具成本效益，其次為5年一次、3年一次、1年一次的肉眼觀察篩查策略及1年一次的巴氏塗片篩查策略。與無篩查幹預相比，如上策略每挽救一個質量調整生命年消耗的成本為11,921至26,069元（1,892-4,138美元，2012年）。同時成本效果分析也顯示，10年一次的肉眼觀察策略最具成本效益，其次為5年一次的肉眼觀察策略及5年一次的巴氏塗片篩查策略。同樣與無篩查幹預相比，如上策略每挽救一個生命年消耗的成本為37,211至68,226元（5,906-18,830美元，2012年）。 / 對於某一既定策略，相應的ICUR和ICER受當地經濟狀況相關因素的影響最大，這些因素包括治療成本、篩查成本和成本貼現率。從檢測技術水平上看，肉眼觀察對分析結果的影響小於巴氏塗片，原因是前者敏感度範圍較小。篩查覆蓋率、初篩陽性隨訪率、診斷陽性治療率也都與相應的ICUR和ICER呈負相關性。敏感性分析結果顯示本文中模型對於健康結局的預測，及相關的衛生經濟學分析，受自然史模型中HPV感染和CIN之間轉移概率的不確定性的影響最大。HPV感染與CIN間的進展和逆轉概率是該項模型研究的核心參數。 / 結論： / 本文中成本效用和成本效果分析均顯示，相較於傳統的細胞學篩查策略，採用間隔時間較長（10年或5年）的肉眼觀察篩查策略，對一般發病地區的35-59歲的農村婦女來說，是更具‘成本效益’的選擇。對於宮頸癌高發地區，其篩查頻率可以提高到1年一次。1年一次的巴氏塗片篩查策略，是最有效的篩查策略，可以挽救最多的生命。但採用該策略時，應在財政預算允許的前提下，確保篩查技術和項目完成的質量。 / 篩查項目的高覆蓋率，對篩查陽性患者良好的隨訪和診治，初篩檢測技術平均水平以上的表現，以及較低的篩查和治療成本是確保篩查項目具備成本效益優勢的核心因素。本文完成的成本效用及成本效果分析，能夠為公共衛生決策提供重要的輔助作用。 / Background: / A Chinese government-sponsored cytology/visual inspection pilot cervical cancer screening program covered 10 million rural women in 221 counties of 31 provinces was initiated in 2009. Both the local and national governments in China need health economic evaluations of feasible strategies so as to make better policies for the next-step enlarging screening. / Objectives: / To perform health economic evaluations of Pap smear and visual inspection cervical cancer screening strategies using population-specific Markov modeling cost-utility (CUA) and cost-effectiveness (CEA) analyses, in order to assist screening policy making for women in rural China. / Methods: / Markov simulation models were developed to synthesize the evidence on costs and health outcomes related to cervical cancer epidemiology in rural China, and applied to predict the long-term utility, effectiveness and costs for hypothetical cohorts of 35-59 years old rural Chinese women, with or without the presence of screening over 20 years. The eight alternative screening strategies assessed were visual inspection with acetic acid (VIA) or traditional cytology (Pap smear) each with ten-year, five-year, three-year and one year screening intervals. / The study was conducted from the societal perspective, thus both directed and non-direct costs related to screening, diagnosis and treatment interventions were considered. The model structures incorporated with the well-accepted the natural history model of cervical cancer and the standard clinical pathway of screening and treatment interventions for precancerous lesions (CIN) and cervical cancer in real practice in rural China. Population-specific data were used as much as possible to be the model inputs. The model estimates were validated by comparison of our predictions of all-cause mortality, cervical cancer mortality and cervical cancer incidence with the national reported data. / Outcome variables included cumulative cost, life years (LYs), quality-adjusted life years (QALYs), predicted reduction(%) in cervical cancer mortality and incidence, relative risk of CIN, relative risk of cervical cancer, incremental cost-utility ratio (ICUR, presented as cost per QALY saved) and incremental cost-effectiveness ratio (ICER, presented as cost per life year saved). Compared with no screening, not-dominated strategies with ICUR and ICER less than three times China’s GDP per capita (76,824 CNY, 2009) were considered to be ‘cost-effective’ options. Among the identified ‘cost-effective’ options, the strategy with lowest ICUR or ICER was defined as the most cost-effective strategy, and the strategy with the highest health benefit (largest QALY saved or life year saved) was defined as the most effective strategy. Sensitivity analyses were conducted to test the effect of uncertainties on decision making. / Results: / All of the VIA and Pap smear screening strategies of showed certain benefits due to the decreased number of women developing cervical cancer, when compared with no screening. A trend for shorter screening interval to have greater benefit was also found. Cervical cancer mortality and incidence were expected to be reduced by 6.67-31.95% and 5.12-24.71% with different screening strategies. And the predicted relative risks of CIN and invasive cervical cancer of 0.89-0.98 and 0.73-0.95, respectively, also demonstrated the protective effect of screenings. / Modeling cost-utility analysis identified ten years VIA screening as the most cost-effective strategy followed by VIA screening with five-, three- and one year interval and Pap smear screening with a one year interval. Compared with no screening, the incremental costs per QALY saved of these strategies ranged from 11,921 to 26,069 Yuan (1,892-4,138 US dollars, 2012). In the meanwhile, modeling cost-effectiveness analysis also identified ten-years VIA screening as the most cost-effective strategy followed by VIA screening with five-year intervals and Pap smear screening with five-year intervals. Compared with no screening, the incremental costs per life year saved of these strategies ranged from 37,211 to 68,226 Yuan (5,906-18,830 US dollars, 2012). / Both ICUR and ICER of a selelected strategy were greatest influnced by factors related to variations in local economies , including treatment cost, screening cost and discounting rate of the cost. The influence of primary test performance of VIA was rather less than that of Pap smear due to the narrower ranges of the VIA sensitivities. Screening coverage, follow-up rate and treatment rate were also negatively associated with ICUR and ICER. Health outcome predictions and health economic analyses were mostly influenced by the uncertainties in HPV infection and CIN transitions in the natural history. Progression and regression probabilities between HPV infection and CIN were considered to be the key parameters of the simulation models. / Conclusions: / Baseline CUA and CEA results suggested that in comparison with traditional cytology screening strategies, organized VIA screening with long intervals (ten or five years) were more cost-effective options than for 35-59 years old women in normal incidence areas of rural China. The VIA screening interval can be shorten to one year in high incidence areas. Pap smear strategy with one year interval can be utilized as the most effective strategy with most lives saved when budget allows and the performances of program and test are ensured. / High coverage of the screening program, good management of screening positives, average or above performance of primary test, and lower screening and treatment costs are key elements for a cost-effective screening program. Cost-utility and cost-effectiveness analyses, such as the one conducted in this thesis study, can be considered important adjuncts to policy decision-making about public health objectives. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Li, Xue. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 388-401). / Abstracts also in Chinese; appendixes includes Chinese. / Abstract of thesis --- p.i / 中文摘要 --- p.v / ACKNOWLEDGEMENTS --- p.viii / TABLE OF CONTENTS --- p.1 / LIST OF TABLES --- p.8 / LIST OF FIGURES --- p.11 / ABBREVIATIONS --- p.12 / Chapter CHAPTER 1 --- INTRODUCTION --- p.14 / Chapter 1.1 --- Epidemiological patterns and disease burden of cervical cancer --- p.14 / Chapter 1.1.1 --- Cervical cancer incidence and mortality worldwide --- p.14 / Chapter 1.1.2 --- Risk factors for cervical cancer --- p.15 / Chapter 1.1.2.1 --- Human Papillomavirus (HPV) --- p.15 / Chapter 1.1.2.2 --- Parity --- p.16 / Chapter 1.1.2.3 --- Smoking --- p.16 / Chapter 1.1.2.4 --- Human Immunodeficiency Virus (HIV) --- p.17 / Chapter 1.1.2.5 --- Contraception --- p.17 / Chapter 1.1.2.6 --- Sexual behavior, nutrition and other factors --- p.18 / Chapter 1.1.3 --- Disease burden of cervical cancer in China --- p.18 / Chapter 1.1.3.1 --- Epidemiology of Cervical Cancer in China --- p.18 / Chapter 1.1.3.2 --- Cervical cancer in different geographic areas of China --- p.20 / Chapter 1.2 --- The need for cost-effectiveness analysis of cervical screening strategies in China --- p.21 / Chapter 1.2.1 --- Cervical cancer prevention in China --- p.21 / Chapter 1.2.2 --- Why do we need a modeling cost-effectiveness analysis? --- p.23 / Chapter 1.3 --- Natural history of cervical cancer --- p.25 / Chapter 1.3.1 --- Terminology --- p.25 / Chapter 1.3.2 --- Natural history of cervical cancer --- p.27 / Chapter 1.4 --- Secondary prevention strategies of cervical cancer --- p.29 / Chapter 1.4.1 --- Screening tests --- p.29 / Chapter 1.4.1.1 --- Cervical cytology --- p.29 / Chapter 1.4.1.2 --- Visual Inspection --- p.32 / Chapter 1.4.1.3 --- HPV testing --- p.36 / Chapter 1.4.2 --- Summary of different screening strategies all over the world --- p.37 / Chapter CHAPTER 2 --- LITERATURE REVIEW --- p.40 / Chapter 2.1 --- Background --- p.40 / Chapter 2.2 --- Objectives of the literature review --- p.41 / Chapter 2.3 --- Search strategies and results --- p.41 / Chapter 2.3.1 --- Search strategies --- p.41 / Chapter 2.3.2 --- Inclusion and exclusion criteria --- p.42 / Chapter 2.4 --- Literature results summary --- p.44 / Chapter 2.4.1 --- Methodology, target population and analytical perspective --- p.44 / Chapter 2.4.2 --- Screening test and program performance --- p.47 / Chapter 2.4.3 --- Cost and utility estimation --- p.49 / Chapter 2.4.4 --- Model parameter sources and validation --- p.53 / Chapter 2.4.5 --- Alternatives and identified cost-effective strategies --- p.58 / Chapter 2.5 --- Conclusions --- p.63 / Chapter CHAPTER 3 --- OBJECTIVES --- p.64 / Chapter 3.1 --- General Objectives --- p.64 / Chapter 3.2 --- Alternative cervical cancer screening strategies in this study --- p.64 / Chapter 3.3 --- Decision rules for recommended cost-effective options --- p.65 / Chapter 3.4 --- Analytical perspective and time horizon --- p.65 / Chapter 3.5 --- Objectives --- p.66 / Chapter 3.6 --- Analytical scenario in this study --- p.66 / Chapter 3.6.1 --- Patterns of cervical screening program delivery in rural China --- p.67 / Chapter 3.6.2 --- Demographic profile of the simulated hypothetical cohort --- p.67 / Chapter 3.6.3 --- Summary of model assumptions --- p.68 / Chapter 3.6.3.1 --- Assumptions related to screening performance and clinical practice --- p.68 / Chapter 3.6.3.2 --- Assumptions related to epidemiological characteristics of cervical cancer --- p.68 / Chapter 3.6.3.3 --- Assumptions related to economic evaluation --- p.69 / Chapter CHAPTER 4 --- METHODOLOGY --- p.70 / Chapter 4.1 --- Alternative strategies in this study --- p.70 / Chapter 4.2 --- Markov Model Developments and Applications --- p.72 / Chapter 4.2.1 --- General introduction of Markov Transition Model --- p.72 / Chapter 4.2.2 --- Structure of Markov models --- p.76 / Chapter 4.2.2.1 --- Natural history model of cervical cancer --- p.76 / Chapter 4.2.2.2 --- Structure of Pap smear and Visual Inspection screening models --- p.82 / Chapter 4.2.2.3 --- Structure of precancerous lesion and invasive cancer treatment models --- p.83 / Chapter 4.2.2.4 --- Interaction of the models --- p.85 / Chapter 4.2.3 --- Demographic profile of the hypothetical cohort --- p.86 / Chapter 4.2.4 --- Probabilities --- p.88 / Chapter 4.2.4.1 --- Identification and converting between rate and probability --- p.89 / Chapter 4.2.4.2 --- Initial probabilities --- p.90 / Chapter 4.2.4.3 --- Transition probabilities --- p.91 / Chapter 4.2.5 --- Screening, diagnosis and treatment characteristics --- p.101 / Chapter 4.2.5.1 --- Screening program characteristics --- p.101 / Chapter 4.2.5.2 --- Diagnosis test performance --- p.104 / Chapter 4.2.5.3 --- Precancerous lesions treatment characteristics --- p.104 / Chapter 4.2.5.4 --- Invasive cancer and treatment characteristics --- p.106 / Chapter 4.2.6 --- Model validation --- p.111 / Chapter 4.3 --- Cost data collection --- p.112 / Chapter 4.3.1 --- Perspective of study --- p.112 / Chapter 4.3.2 --- Selection of study sites --- p.113 / Chapter 4.3.3 --- Screening cost data collection --- p.113 / Chapter 4.3.4 --- Treatment cost data collection --- p.115 / Chapter 4.4 --- Cost-utility analysis and cost-effectiveness analysis --- p.117 / Chapter 4.4.1 --- General introduction of these two analyses --- p.117 / Chapter 4.4.2 --- Utility Estimates --- p.118 / Chapter 4.4.3 --- Screening utility and effectiveness evaluation --- p.120 / Chapter 4.4.4 --- Cost-effectiveness and cost-utility analysis method --- p.122 / Chapter 4.5 --- Time horizon and discounting rate --- p.125 / Chapter 4.6 --- Summary of modeling assumptions --- p.126 / Chapter 4.6.1 --- Assumptions related to screening performance and clinical practice --- p.126 / Chapter 4.6.2 --- Assumptions related to epidemiological characteristics of cervical cancer --- p.127 / Chapter 4.6.3 --- Assumptions related to economic evaluation --- p.128 / Chapter 4.7 --- Sensitivity analysis --- p.128 / Chapter 4.8 --- Ethical approval --- p.129 / Chapter CHAPTER 5 --- RESULTS --- p.130 / Chapter 5.1 --- Model validation --- p.130 / Chapter 5.2 --- Cost analysis results --- p.134 / Chapter 5.2.1 --- Screening costs results --- p.134 / Chapter 5.2.2 --- Treatment cost results --- p.136 / Chapter 5.2.3 --- The proportional costs breakdown for different screening strategies --- p.139 / Chapter 5.3 --- Utility estimation results --- p.141 / Chapter 5.4 --- Cost-utility analysis results --- p.144 / Chapter 5.4.1 --- Baseline analysis --- p.144 / Chapter 5.4.2 --- Influence of screening program performance --- p.148 / Chapter 5.4.2.1 --- Coverage of the screening program --- p.148 / Chapter 5.4.2.2 --- Follow up rate and treatment rate of positives --- p.155 / Chapter 5.4.3 --- Influence of screening test performance --- p.159 / Chapter 5.4.4 --- Influence of costs --- p.165 / Chapter 5.4.4.1 --- Influence of screening costs --- p.165 / Chapter 5.4.4.2 --- Influence of treatment costs --- p.168 / Chapter 5.4.5 --- Influence of discounting --- p.171 / Chapter 5.4.6 --- Summary of factors and their influences on the baseline CUA results --- p.174 / Chapter 5.5 --- Cost-Effectiveness analysis results --- p.180 / Chapter 5.5.1 --- Baseline analysis --- p.180 / Chapter 5.5.1.1 --- Life year saved --- p.181 / Chapter 5.5.1.2 --- Cervical cancer mortality reduction --- p.185 / Chapter 5.5.1.3 --- Cervical cancer incidence reduction --- p.187 / Chapter 5.5.1.4 --- Relative risk of CIN and cervical cancer --- p.189 / Chapter 5.5.1.5 --- Effectiveness summary of alternative screening strategies on the hypothetical 100,000 rural Chinese women --- p.191 / Chapter 5.5.2 --- Factors that influence the CEA results --- p.195 / Chapter 5.5.2.1 --- Best scenario analysis --- p.196 / Chapter 5.5.2.2 --- Worst scenario analysis --- p.201 / Chapter 5.5.2.3 --- Summary of the possible ranges of costs and effectiveness in different scenarios --- p.206 / Chapter 5.6 --- Sensitivity analysis --- p.209 / Chapter 5.6.1 --- Sensitivity analysis of Cost-Utility analysis results --- p.209 / Chapter 5.6.1.1 --- Tornado analysis --- p.209 / Chapter 5.6.1.2 --- One-way sensitivity analysis --- p.213 / Chapter 5.6.2 --- Sensitivity analysis of Cost-Effectiveness analysis results --- p.220 / Chapter 5.6.2.1 --- Tornado analysis --- p.220 / Chapter 5.6.2.2 --- One-way sensitivity --- p.224 / Chapter 5.6.3 --- Summary of sensitivity results --- p.236 / Chapter CHAPTER 6 --- SUMMARY, DISSICUSSION AND CONCLUSIONS --- p.240 / Chapter 6.1 --- Summary of Markov model development and validation --- p.240 / Chapter 6.1.1 --- Category and source summary of input parameters --- p.240 / Chapter 6.1.2 --- Model validation --- p.244 / Chapter 6.2 --- Summary of modeling results --- p.245 / Chapter 6.2.1 --- Summary of Cost-Utility Analysis --- p.245 / Chapter 6.2.1.2 --- Baseline analysis findings --- p.245 / Chapter 6.2.1.2 --- Influential factors on the cost-effective manner of alternative strategies --- p.246 / Chapter 6.2.2 --- Summary of Cost-Effectiveness Analysis --- p.250 / Chapter 6.2.2.1 --- Baseline analysis findings --- p.251 / Chapter 6.2.2.2 --- Possible ranges for cost and effectiveness of alternative strategies under different scenarios --- p.253 / Chapter 6.2.3 --- Summary of CUA and CEA findings --- p.257 / Chapter 6.2.4 --- Summary of sensitivity analysis --- p.259 / Chapter 6.2.4.1 --- Important variables on health outcome predictions --- p.259 / Chapter 6.2.4.2 --- Sensitive variables to the baseline CUA and CEA recommendations --- p.260 / Chapter 6.2.4.3 --- Overview of the sensitivity analysis --- p.263 / Chapter 6.3 --- Discussion --- p.264 / Chapter 6.3.1 --- Alternative strategies of cervical cancer screening in rural China --- p.264 / Chapter 6.3.1.1 --- Target ages --- p.265 / Chapter 6.3.1.2 --- Screening intervals --- p.266 / Chapter 6.3.1.3 --- Feasible primary screening tests --- p.267 / Chapter 6.3.1.4 --- Service delivering patterns --- p.269 / Chapter 6.3.1.5 --- Time horizon of this thesis study --- p.270 / Chapter 6.3.2 --- Transition probability estimation --- p.271 / Chapter 6.3.3 --- Screening and treatment cost estimation --- p.276 / Chapter 6.3.3.1 --- Representativeness of the selected counties --- p.276 / Chapter 6.3.3.2 --- Screening costs of VIA and Pap smear --- p.277 / Chapter 6.3.3.3 --- Treatment costs --- p.279 / Chapter 6.3.4 --- Utility estimation --- p.280 / Chapter 6.3.4.1 --- Instrument selection --- p.280 / Chapter 6.3.4.2 --- Utility estimation between studies --- p.281 / Chapter 6.3.5 --- Baseline cost-utility and cost-effectiveness analyses --- p.283 / Chapter 6.3.6 --- Sensitivity Analysis --- p.284 / Chapter 6.3.7 --- Strengths and limitations --- p.286 / Chapter 6.3.7.1 --- Limitations --- p.286 / Chapter 6.3.7.2 --- Strengths --- p.288 / Chapter 6.4 --- Policy implications --- p.289 / Chapter 6.4.1 --- How to manage a cost-effective cervical cancer screening program? --- p.289 / Chapter 6.4.2 --- How can VIA screening be adopted? --- p.290 / Chapter 6.4.3 --- How can Pap smear screening be adopted? --- p.291 / Chapter 6.4.4 --- Framework for policy decision making --- p.292 / Chapter 6.5 --- Conclusions --- p.295 / Chapter APPENDIX --- p.300 / Chapter Appendix 1-1 --- The 2001 Bethesda System* --- p.300 / Chapter Appendix 1-2 --- The FIGO Staging for cervical cancers* --- p.301 / Chapter Appendix 1-3 --- Cervical Cancer Screening Program in different countries --- p.302 / Chapter Appendix 4-1 --- WHO World Standardized Population Distribution (%) --- p.305 / Chapter Appendix 4-2 --- Summary of transition probabilities literature review --- p.306 / Chapter Appendix 4-3 --- Price Indices from 1978 to 2010 --- p.326 / Chapter Appendix 4-4 --- Screening Cost Questionnaire --- p.327 / Chapter Appendix 4-5 --- Programmatic Cost Survey Questionnaire --- p.339 / Chapter Appendix 4-6 --- Treatment Cost Survey Questionnaire --- p.342 / Chapter Appendix 4-7 --- EQ-5D Algorism (UK) --- p.344 / Chapter Appendix 4-8 --- Chinese Version of EQ5D----HQOL score questionnaire --- p.345 / Chapter Appendix 5-1 --- Calibrated variables and its final settings --- p.348 / Chapter Appendix 5-2 --- Cervical cancer new cases and deaths all over the world in 2008 --- p.349 / Chapter Appendix 5-3 --- Data distribution of CIN2-3 and cervical cancer treatment costs --- p.350 / Chapter Appendix 5-4 --- Relative risk of CIN and cervical cancer by age groups of alternative screening strategies --- p.361 / Chapter Appendix 5-5 --- Influence of discounting rate of life years on the CEA results --- p.363 / Chapter Appendix 5-6 --- Tornado analysis results based on the effect on QALYs predictions --- p.367 / Chapter Appendix 5-7 --- Tornado analysis results based on the effect on life-year predictions --- p.372 / Chapter Appendix 6-1 --- Summary of Markov Model Inputs and Sources --- p.377 / REFERENCE --- p.388

Thesis (MScMed)--Stellenbosch University, 2004. / Copy not signed by author. / ENGLISH ABSTRACT: This study involved 33 patients, 19 men and 14 women. The age range was wide (20-90 years) and median age was 57 years. These patients had a single pulmonary nodule (SPN) defined radiologically as a well defined, round or oval intrapulmonary lung lesion not associated with atelectasis or adenopathy on chest radiography or computed tomography. Patients were investigated with Tc-99m MIBI and TI-201 (25 patients) and with Tc-99m MIBI alone (8 patients). Single photon emission computed tomography images were reconstructed using both iterative reconstruction (Ordered Subsets - Expectation Maximisation: aSEM) and filtered backprojection (FBP), on the Hermes system. Transverse, coronal and sagittal slices were displayed on the screen using a grey scale. The aSEM and FBP images for each study were co-registered semi-automatically using the multimodality programme on the Hermes. The best slice for the lesion was chosen according to the best view used to locate the SPN on chest radiograph. Regions of interest (Ral) were drawn manually outside the outer margin of the detected lesion, first on the aSEM image. This was automatically mirrored on the co-registered FBP image. For most patients, the background was automatically mirrored horizontally on the contralateral side, again, first on the OSEM then automatically on the FBP image. Automatic vertical mirroring or manual horizontal mirroring was used when background was found to be in a visually 'hot' area like the heart or vertebrae. The average counts and standard deviation of the Ral and background were generated automatically. Semi-quantitative image analysis was done by calculating the signal-to-noise ratio (SNR) and tumour-to-background (TIB) ratio using the following formulae: SNR = Mean counts ROI(lesion) - Mean counts background Standard deviation background TIB rati.o = -M---e-a-n-'--c-o--u-n-'t-s- ROI(lesion) Mean counts background Detection was found to be the same for the two reconstruction algorithms, that is, every lesion detected by using OSEM could also be detected by using FBP. However lesion detection did differ between Tl-201 and Tc-99m-MIBI. Sensitivity and specificity were calculated for different thresholds of SNR and TIB ratios. Receiver operating characteristics (ROC) curves were drawn to represent the different sensitivities and specificities at each threshold. Tuberculosis (TB) was not included in this analysis as uptake of Tl-20l was found to be significantly high and comparable to that of malignant nodules. However the effect of OSEM and FBP on the 'positive' TB nodules was assessed separately. By calculating the area under the ROC curves, TI-201 using OSEM was shown to be more accurate at differentiating malignant nodules from benign ones than FBP. Although this difference was not statistically significant (p=0.1 0), there was a clear tendency. The two reconstruction algorithms were found to be almost equally accurate, when using Tc-99m-MIBI, the difference between them being considerably insignificant. In conclusion, it was shown that there is a tendency that OSEM outperforms FBP for studies using Tl-201 but not for Tc-99m-MIBI. / AFRIKAANSE OPSOMMING: Hierdie studie sluit 33 pasiënte in, 19 mans en 14 vroue. Die ouderdomme wissel tussen 20 en 90 jaar met 'n gemiddelde ouderdom van 57 jaar. Elkeen van die pasiënte het 'n enkel longnodule (SPN) op borskas X-straal en/of rekenaar tomografie getoon, wat radiologies gedefinieer word as 'n goed omskrewe, ronde of ovaal intrapulmonale longletsel wat nie met atelektase of adenopatie geassosieer is nie. Pasiënte is met Tc-99m MIDI en TI-201 (25 pasiënte) of slegs met Tc-99m MIBI (8 pasiënte) ondersoek. Enkelfoton emissie rekenaar tomografiese (EFERT) beelde is met beide iteratiewe rekonstruksie (Ordered Subsets - Expectation Maximisation: OSEM) en gefilterde terugprojeksie (FBP) met die Hermes sisteem gerekonstrueer. Transvers, koronale en sagittale snitte is in grysskaal op die sisteem vertoon. Die OSEM en FBP beelde vir elke studie is semi-outomaties gekoregistreer met behulp van die multimodaliteitsprogram op die Hermes. Die optimale snit vir elke letsel is gekies volgens die beste aansig op die borskas X-straalom die SPN te lokaliseer. Gebiede van belang (ROl) is met die hand buite-om die buitenste rand van die letsel getrek op die OSEM beeld en daarna outomaties in die ooreenstemmende area op die gekoregistreerde FPB beeld geplaas. Vir die meeste pasiënte is die agtergrond outomaties as horisontale spieëlbeeld op die kontralaterale kant geplaas, eers op die OSEM en dan outomaties op die FBP beeld. 'n Outomatiese vertikale spieëlbeeld of manuele horisontale verskuiwing van die agtergrondsarea is gedoen indien die agtergrond oorvleuel het met 'n 'warm' area soos die hart of werwels. Die gemiddelde tellings en standaardafwyking van die ROl en agtergrond is outomaties gegenereer. Semi-kwantitatiewe beeldanalise is gedoen deur berekening van die sein-tot-agtergrond verhouding (signal-to-noise ratio - SNR) en tumor-tot-agtergrond (TIB) verhouding met behulp van die volgende formules: SNR = gemiddelde tellings ROI(letsel) - gemiddelde tellings agtergrond Standaard afwyking van agtergrond TIB rati.o = -g=em--id-d-e-l-d-e--te=ll-in-g-s__R:_O-I(-le-t-s'e-l) gemiddelde tellings agtergrond Opsporing is soortgelyk bevind vir die twee rekonstruksie algoritmes, dit wil sê elke letselopgespoor met behulp van OSEM kon ook met FBP opgespoor word. Letselwaameming het egter verskil tussen TI-201 en Tc-99m-MIBI. Sensitiwiteit en spesifisiteit is vir verskillende drempels van SNR en TIB verhoudings bereken. 'Receiver operating characteristics' (ROC) kurwes is getrek om die verskillende sensitiwiteite en spesifisiteite by elke drempel te verteenwoordig. Tuberkulose (TB) is nie in hierdie analise ingesluit nie aangesien opname van Tl-201 beduidend hoog en vergelykbaar met die van maligne nodules was. Die effek van OSEM en FBP op die 'positiewe' TB nodules is egter apart beoordeel. Deur berekening van die area onder die ROC kurwes, is getoon dat OSEM van Tl-201 tomografiese data meer akkuraat as FBP was om maligne van benigne nodules te onderskei. Alhoewel hierdie verskil nie statisties betekenisvol was nie (p=0.10), is daar wel 'n duidelike neiging gevind. Die twee rekonstruksie algoritmes was byna ewe akkuraat wanneer Tc-99m-MIBI gebruik is, met duidelik geen betekenisvolle verskil tussen die algoritmes nie. Gevo lgtrekking In hierdie studie is dit getoon dat daar 'n neiging is dat OSEM beter vaar as FBP vir studies met tallium-201 maar nie vir Tc-99m-MIBI nie.

Background: A global cervical cancer health disparity persists despite the demonstrated success of primary and secondary preventive strategies, such as cervical visual inspection (VI). Cervical cancer is the leading cause of cancer incidence and death for women in many low resource areas. The greatest risk is for those who are unable or unwilling to access screening. Barriers include healthcare personnel shortages, cost, transportation, and mistrust of healthcare providers and systems. Using community health workers (CHWs) may overcome these barriers, increase facilitators, and improve participation in screening for women in remote areas with limited access to clinical resources. Aim: To determine whether the accuracy of VI performed by CHWs was comparable to VI by physicians or nurses and to consider the affect components of provider training had on VI accuracy. Methods: A systematic review and quantitative meta-analysis of published literature reporting on VI accuracy, provider type, and training was conducted. Strict inclusion/exclusion criteria, study quality, and publication bias assessments improved rigor and bivariate linear mixed modeling (BLMM) was used to determine the affect of predictors on accuracy. Unconditional and conditional BLMMs, controlling for VI technique, provider type, community, clinical setting, HIV status, and gynecological symptoms were considered. Results: Provider type was a significant predictor of sensitivity (p=.048) in the unconditional VI model. VI performed by CHWs was 15% more sensitive than physicians (p=.014). Provider type was not a significant predictor of accuracy in any other models. Didactic and mentored hours predicted sensitivity in both BLMMs. Quality assurance and use of a training manual predicted specificity in unconditional BLMMs, but was not significant in conditional models. Number of training days, with ≤5 being optimal, predicted sensitivity in both BLMMs and specificity in the unconditional model. Conclusion: Study results suggest that community based cervical cancer screening with VI conducted by CHWs can be as, if not more, accurate than VI performed by licensed providers. Locally based screening programs could increase access to screening for women in remote areas. Collaborative partnerships in “pragmatic solidarity” between healthcare systems, CHWs, and the community could promote participation in screening resulting in decreased cervical cancer incidence and mortality. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2016. / FAU Electronic Theses and Dissertations Collection

Bakgrund: Cancer är en diagnos som ökar i samhället, en ökning som ses fortsätta. Att ta emot ett cancerbesked och genomgå behandling kräver stöd från hälso- och sjukvården. Genom samtal ges möjlighet till delaktighet och en omvårdnad där patienten står i centrum. Sjuksköterskan behöver ha kunskap kring kommunikation för att bemöta patienten på bästa sätt. Viktigt är att säkerställa att patienten mottagit och förstått informationen. Syfte: Att belysa patientens upplevelse av samtal med sjuksköterska vid cancerdiagnos. Metod: En kvalitativ analys av narrativer har använts för granskning av sex självbiografier, skrivna av personer med erfarenhet av cancerdiagnos. Resultat: Resultatet belyser följande kategorier: samtal som vårdar, delaktighet i samtalet, hoppfullhet i orden, vill inte höra samt upplevelse av rädsla. Konklusion: Samtalet visar sig vara betydelsefullt i mötet mellan patient och sjuksköterska. Hur sjuksköterskan uttrycker sig och bemöter patienten påverkar upplevelsen av samtalet och vilken utgång samtalet får. / Background: Cancer is a diagnosis that is increasing in society, an increase seen to continue. Receiving a cancer message and undergoing treatment requires support from the health service. Through conversation, the opportunity is given for participation and a care where the patient is in the center. The nurse needs to have knowledge about communication to respond to the patient in the best way. It is important to ensure that the patient has received the information correctly. Aim: To illustrate the patient's experience of conversation with nurse during cancer diagnosis. Method: A qualitative analysis of narratives has been used for examination of six autobiographies, written by persons with experience of cancer diagnosis. Result: The result highlights the following categories: conversations that cherish, participation in the conversation, hopefulness in words, don’t want to hear and experience of fear. Conclusion: The conversation turns out to be important in the meeting between the patient and the nurse. How the nurse expresses her/himself and responds to the patient affects the experience of the conversation and what outcome the conversation gets.