Abstract Hip fracture causes substantial burden for individual and society, with increased mortality and loss of function. The purpose of this study was to (1) examine the effects of specialized (physical and geriatric) rehabilitation on home-dwelling hip fracture patients 50 years or older on recovery one year after the fracture, (2) to evaluate the costs and cost-effectiveness of specialized rehabilitation modalities, (3) to study the recovery after hip fracture between home-dwelling male and female patients and (4) to determine recommendations for hip fracture rehabilitation concerning the general rehabilitation practices in Finland. A total of 538 consecutively, independently living patients with non-pathological hip fracture treated in Oulu University hospital, were randomized to one of the three rehabilitation modalities: privately-based rehabilitation unit (physical rehabilitation), geriatric department (geriatric rehabilitation) and healthcare centre hospital (control group). Patients were evaluated on admission, at 4 and 12 months for social status, residential status, walking ability, use of walking aids, pain in the hip, activities of daily living and mortality. Costs were evaluated by recording the use of healthcare service and the prices were obtained from Diagnosis Related Group (DRG) price list for the hospital and from a publication of the National Research and Development Centre for Welfare and Health. Mortality was lower in the physical rehabilitation group 4 and 12 months after the fracture compared to geriatric and the control rehabilitation group. Physical and geriatric rehabilitation improved the ability of independent living after 4 months, but this effect could not be seen after 12 months. The rehabilitation costs were higher in the physical rehabilitation than in the control group, but the total healthcare-related costs one year after the fracture were lower in the physical rehabilitation group than in the control. Male and female patients recovered similarly after hip fracture. Age, poor functional status before the fracture and high ASA-score increased the mortality risk. This thesis suggests that intensive mobilization and rehabilitation is a recommended practice after the hip fracture, resulting in better functional recovery, survival and lower economic costs compared to routine treatment. Poor recovery was predicted not by sex, but by prefracture function and morbidity. / Tiivistelmä Lonkkamurtuma on yksi merkittävimmistä toimintakyvyn laskua ja kuolleisuutta aiheuttavista vammoista. Tämän väitöskirjatutkimuksen tarkoituksena oli (1) tutkia tehostetun (fysikaalisen ja geriatrisen) kuntoutuksen vaikutusta itsenäisesti asuvien, vähintään 50-vuotiaiden lonkkamurtumapotilaiden kuntoutumiseen murtumaa seuraavan vuoden aikana, (2) arvioida lonkkamurtuman hoidon kustannuksia ja kustannusvaikuttavuutta tehostetussa kuntoutusyksikössä, (3) tutkia lonkkamurtuman kuntoutumisen eroja mies- ja naispotilaiden välillä sekä (4) tarkentaa lonkkamurtuman hoitoketjun yleisiä suosituksia Suomessa. Tutkimuksessa seurattiin 538 lonkkamurtumapotilasta, jotka hoidettiin kirurgisesti Oulun yliopistollisessa sairaalassa. Valintakriteereihin kuului vähintään 50 vuoden ikä sekä kyky itsenäiseen asumiseen joko omassa kodissa tai kodinomaisessa ympäristössä ennen murtumaa. Lonkkaleikkauksen jälkeen potilaat satunnaistettiin yhteen kolmesta kuntoutusryhmästä: fysikaaliseen kuntoutusryhmään (Oulun Diakonissalaitos), geriatriseen kuntoutusryhmään (Oulun kaupunginsairaalan kuntoutusosasto) sekä kontrolliryhmään (terveyskeskussairaalassa tapahtuva kuntoutus). Seuranta-aika oli yksi vuosi. Potilaat haastateltiin ennen kuntoutusta, sekä neljän ja 12 kuukauden kuluttua murtumasta, joiden yhteydessä aineisto kerättiin koskien yleistä terveydentilaa, toiminta- ja kävelykykyä, asumismuotoa ja kuolleisuutta. Kustannukset arvioitiin terveyspalveluiden käytöstä ja näiden hintoina käytettiin sairaalan yksikköhintoja (DRG) ja sosiaali- ja terveysalan tutkimus- ja kehittämiskeskuksen (STAKES) yksikköhintoja. Fysikaalinen kuntoutus vähensi merkittävästi potilaiden kuolleisuutta neljän ja 12 kuukauden seurannoissa verrattuna geriatriseen kuntoutukseen sekä kontrolliryhmään. Lisäksi fysikaalinen ja geriatrinen kuntoutus lisäsivät lyhytaikaisesti potilaiden kykyä itsenäiseen asumiseen verrattuna kontrolliryhmään. Taloudellisten vaikutusten osalta fysikaalinen kuntoutusjakso oli huomattavasti tavanomaista kuntoutusta kalliimpi, mutta fysikaalisen kuntoutusryhmän kokonaiskustannukset vuoden aikana olivat pienemmät kuin kontrolliryhmän potilailla. Sukupuolella ei ollut vaikutusta potilaiden toimintakykyyn, laitostumiseen tai kuolleisuusriskiin murtuman jälkeen. Merkittäviksi kuolleisuutta ennustaviksi tekijöiksi osoittautuivat ikä, toimintakyky ennen murtumaa sekä leikkauskelpoisuusluokitus. Tulokset puoltavat tehostetun, erikoistuneessa kuntoutusyksikössä suoritetun hoidon käyttöä lonkkamurtumapotilailla sekä terveydellisten että taloudellisten syiden osalta.

The purpose of this research project is to develop concepts for doing cost-benefit analyses for governmental and nonprofit homes. Such concepts should facilitate a differential diagnosis which recognizes the wide individual differences among those served. Developing relevant concepts is a first step in measurement. An aim is to develop appropriate concepts and instruments that will make an ordinal measurement of resident satisfaction possible. This study makes no effort to develop monetary measures of either costs or benefits. These measures and the related cost-benefit analyses must await further developments. Of the home's employees, the nurses and nurses' assistants usually have the most prolonged and intimate contact with the residents. The nurses and nurses' assistants often are the home personified in that they provide the bulk of a home's services to the less able residents. This explains why the environment of the home, which includes the values, needs, and attitudes of nurses and nurses' assistants, is believed to influence resident satisfaction.

目的：針對心血管初級預防，世界各國均推薦某一年齡段人群全部測量膽固醇以估算心血管病發病風險。此舉耗費高且非必須，本研究旨在建立並驗證一個新型的选择性膽固醇篩查模型，用以篩查需藥物治療之高危人群，并在成本效益方面與其它篩查模型相比較。 / 方法：本模型具體采用兩步法：首先利用一個足夠高的假設膽固醇值代入心血管病風險預測方程，用以系統性的高估絶大多數人的心血管病風險；其次只有假設心血管病風險高於推薦治療閾值時，該個體才需要測量膽固醇，並進行實際心血管病風險分析。 / 英国健康调查和中国营养与健康调查是本次研究的合适数据。我們首先探索最優的假設膽固醇值，尋找到最後膽固醇值之後，我們將繼續測試我們的新型膽固醇篩查模型，在不同的治療閾值下，表現是否穩定。我們以靈敏度，特異度和徐篩查人群為指標，比較我們模型與全民篩查模型和英國NICE 選擇篩查模型相比較。之後我們估算在中英人群中應用該篩查模型，所需耗費的成本和可預防心血管事件數。 / 结果：與全名篩查模型相比，我們的模型靈敏度相若但可以節省80%左右的篩查費用。模型的靈敏度主要取決於所採用的假設膽固醇值，與所用風險預測方程，治療閾值和人群心血管風險分佈無關。當以均數加2 倍標準差作為假設膽固醇值時，靈敏度可達到97.5%左右，特異度可以達到90%左右，符合預期。模型應用於中國人群得到的結果類似。值得註意的是，在中國人群中，即使不測量膽固醇，模型靈敏度亦接近95%。此外，將膽固醇篩查項目限制于男性50-84歲，女性60-84 歲年齡段可以進一步減少篩檢費用。在人群影響方面，我們模型可預防心血管事件數比全名篩查模型略少，但成本大大降低。英國NICE 模型適用於某些特定情況，但並非全部。 / 結論：我們的新型篩查模型靈敏度與全民篩查模型相若，但可以節省大量篩查費用。在资源匮乏地区，可考虑在某一特定年龄段运用我们的模型已达到进一步减少费用的效果。如果本研究结果得到进一步数据证实，對於中國人群而言，膽固醇測量可能並非心血管風險評估所必須。 / Objectives / Since the mid 1990s, most guidelines on primary prevention of cardiovascular disease (CVD) have recommended regular cholesterol measurement for all adults or those above a certain age (which is known as mass screening). Cholesterol measurement comprises a large cost of CVD prevention and is not necessarily required in those who do not need drug intervention. In order to reduce this cost, we have developed a new selective cholesterol screening model in order to determine whose cholesterol should be measured for drug prevention. The model was evaluated and compared with other widely adopted models in basic model performance as well as cost effectiveness. / Methods / The new model has two steps. In the first step, we purposely over-estimated the majority of respondents’ CVD risk by substituting a sufficiently high hypothetical cholesterol value in the risk estimation. We then recommend cholesterol measurement only to those with the estimated CVD risk above a predetermined risk threshold for drug treatment. In the second step, the CVD risk is re-estimated based on the individual’s real cholesterol consentration. Those with a risk above the treatment threshold are recommended for drug treatment. / We evaluated the performance of our two-step model with data from the Health Survey for England and re-evaluated it with data from the China Nutrition and Health Survey 2002. By varying the hypothetical cholesterol values and treatment thresholds in CVD risk, we assessed the sensitivity, specificity and proportion of the population who need to measure cholesterol and compared it with the US mass screening model and the UK NICE selective screening model. We further compared the costs and CVD events avoided in the compared screening programmes. We also examined how the age restriction should be set in cholesterol screening programmes. / Results / As compared to mass screening, our new model can achieve a high sensitivity and save some 80% the cost of cholesterol measurements. The sensitivity depends mainly on the hypothetical cholesterol level used and seems independent of population’s CVD risk, treatment cut-off values and risk prediction model. The model performed well in almost all the conditions tested. When the hypothetical cholesterol was set at MEAN+2SD, the resulting sensitivity of our selective screening model was almost always above 95% and close to the expected 97.5%. The sensitivity was only compromised slightly if cholesterol is not measured at all for the Chinese population. Furthermore, in order to save more costs, cholesterol measurement could be better restricted to men aged 50-84 and women 60-84 years regardless of the screening model used. In CVD events prevented, mass screening is always the best but our model can prevent almost as many. In costs, mass screening is always the most expensive but our model can save all or most of the cost. The NICE selective model can perform as well as our model only when it is used in an appropriate manner and in certain circumstances. / Conclusion / Our new cholesterol screening model has a high sensitivity which is comparable to that of universal screening programs but can save most of the cost on cholesterol measurements. In where resources are particular sparse, our model can also perform well by applying it only to certain age groups, which will further save cholesterol measurement costs. Cholesterol measurement could even be completely avoided for the Chinese population if our findings can be re-confirmed correct with more updated data. / 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. / Hu, Xuefeng. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 114-121). / Abstract also in Chinese. / Abstract (in English) --- p.i / Abstract (in Chinese) --- p.iv / Acknowledgements --- p.vi / Abbreviations used in the thesis --- p.viii / List of Tables --- p.xvi / List of Figures --- p.xviii / List of Boxes --- p.xix / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- The burden of cardiovascular disease --- p.1 / Chapter 1.2 --- Primary prevention of CVD --- p.2 / Chapter 1.3 --- The high-risk individual strategy for CVD primary prevention --- p.3 / Chapter 1.3.1 --- The high risk individual strategy is effective --- p.4 / Chapter 1.3.2 --- The high risk individual strategy is cost-effective --- p.4 / Chapter 1.4 --- Who should be treated with drugs? --- p.5 / Chapter 1.4.1 --- The single risk factor strategy --- p.5 / Chapter 1.4.2 --- The overall CVD risk strategy --- p.7 / Chapter 1.4.3 --- Scope of CVD primary prevention --- p.8 / Chapter 1.5 --- Methods for assessing the CVD risk --- p.9 / Chapter 1.6 --- Current strategies for cholesterol measurements --- p.10 / Chapter 1.6.1 --- United States National Cholesterol Education Program --- p.13 / Chapter 1.6.2 --- American Heart Association CVD and Stroke prevention guideline --- p.14 / Chapter 1.6.3 --- The U.S. Preventive Services Task Force guideline --- p.15 / Chapter 1.6.4 --- New Zealand guideline 2003 --- p.16 / Chapter 1.6.5 --- Australian guideline 2009 --- p.17 / Chapter 1.6.6 --- The Joint British Society guideline-2 --- p.17 / Chapter 1.6.7 --- UK Department of Health guideline on vascular check --- p.18 / Chapter 1.6.8 --- China Blood Lipid Modification Guideline 2007 --- p.18 / Chapter 1.6.9 --- Summary of the reviewed guidelines --- p.19 / Chapter 1.7 --- Rationale for a selective screening model --- p.20 / Chapter 1.8 --- The UK NICE model --- p.22 / Chapter 1.9 --- Objectives of this study --- p.24 / Chapter 2 --- Methods --- p.25 / Chapter 2.1 --- The new cholesterol screening model --- p.25 / Chapter 2.2 --- Framework for evaluating the new screening model --- p.27 / Chapter 2.3 --- Indexes for evaluating the basic performance of screening models --- p.28 / Chapter 2.3.1 --- Sensitivity, specificity and % need cholesterol measurement --- p.28 / Chapter 2.3.2 --- Sensitivity analysis for model performance --- p.29 / Chapter 2.3.2.1 --- Using different hypothetical cholesterol values --- p.29 / Chapter 2.3.2.2 --- Using different treatment cut-off thresholds --- p.30 / Chapter 2.3.2.3 --- Using different populations --- p.30 / Chapter 2.3.2.4 --- Using different risk equations --- p.31 / Chapter 2.4 --- Data --- p.31 / Chapter 2.4.1 --- The Health Survey for England --- p.31 / Chapter 2.4.1.1 --- Background and aim of the survey --- p.31 / Chapter 2.4.1.2 --- Survey design --- p.32 / Chapter 2.4.1.2.1 --- Sampling Frame --- p.32 / Chapter 2.4.1.2.2 --- Weighting variables --- p.33 / Chapter 2.4.1.3 --- Data collection --- p.33 / Chapter 2.4.1.3.1 --- Blood cholesterol --- p.34 / Chapter 2.4.1.3.2 --- Blood pressure --- p.34 / Chapter 2.4.1.3.3 --- Smoking --- p.34 / Chapter 2.4.1.3.4 --- History of CVD and diabetes --- p.34 / Chapter 2.4.1.3.5 --- Treatment history --- p.35 / Chapter 2.4.2 --- The 2002 China National Nutrition and Health Survey --- p.35 / Chapter 2.4.2.1 --- Survey design --- p.36 / Chapter 2.4.2.2 --- Data collection --- p.36 / Chapter 2.4.2.2.1 --- Blood pressure --- p.36 / Chapter 2.4.2.2.2 --- Blood cholesterol --- p.38 / Chapter 2.4.2.2.3 --- Smoking --- p.38 / Chapter 2.4.2.2.4 --- History of CVD, diabetes and drug treatment --- p.38 / Chapter 2.4.3 --- Subjects eligible for analysis in this study --- p.38 / Chapter 2.5 --- CVD risk prediction --- p.43 / Chapter 2.5.1 --- The Framingham risk equation for the UK population --- p.43 / Chapter 2.5.2 --- The Asian equation for the Chinese population --- p.44 / Chapter 2.5.3 --- Adjusting for cholesterol and blood pressure --- p.45 / Chapter 2.5.4 --- Deriving the hypothetical cholesterol --- p.46 / Chapter 2.6 --- Identifying the appropriate age ranges for cholesterol measurement --- p.47 / Chapter 2.7 --- Comparing various screening models and options --- p.47 / Chapter 2.7.1 --- Compared screening models and options --- p.47 / Chapter 2.7.1 --- Indices for the performance of the screening options --- p.49 / Chapter 2.7.2 --- Costs of different screening options --- p.50 / Chapter 2.7.2.1 --- Components of screening cost from societal perspective --- p.50 / Chapter 2.7.2.1.1 --- Cost for inviting people for data collection --- p.50 / Chapter 2.7.2.1.2 --- Cost for the full risk assessment --- p.51 / Chapter 2.7.2.1.3 --- Treatment cost --- p.51 / Chapter 2.7.2.1.4 --- Cost saved for avoided CVD events --- p.52 / Chapter 2.7.2.2 --- Components of screening cost from health system’s perspective --- p.52 / Chapter 2.7.3 --- Number of CVD events avoidable --- p.53 / Chapter 2.8 --- Statistical analysis --- p.54 / Chapter 2.8.1 --- Descriptive analysis --- p.54 / Chapter 2.8.2 --- Cross-tabulation analysis --- p.54 / Chapter 2.8.3 --- Survey data analysis --- p.54 / Chapter 3 --- Results --- p.57 / Chapter 3.1 --- Description of data --- p.57 / Chapter 3.1.1 --- The UK population --- p.57 / Chapter 3.1.1.1 --- Sumamry of CVD risk and risk factors --- p.57 / Chapter 3.1.1.2 --- Distribution of age --- p.57 / Chapter 3.1.1.3 --- Distribution of blood pressure and blood cholesterol --- p.58 / Chapter 3.1.1.4 --- Distribution of the predicted 10-year CVD risk --- p.62 / Chapter 3.1.1.5 --- Relation between the risk threshold and age --- p.63 / Chapter 3.1.2 --- The Chinese population --- p.65 / Chapter 3.1.2.1 --- Summary of CVD risk and risk factors --- p.65 / Chapter 3.1.2.2 --- Distribution of age --- p.65 / Chapter 3.1.2.3 --- Distribution of blood pressure and blood cholesterol --- p.66 / Chapter 3.1.2.4 --- Distribution of the predicted 10-year CVD risk --- p.69 / Chapter 3.1.2.5 --- Relation between the risk threshold and age --- p.70 / Chapter 3.2 --- Performance of our new screening model --- p.72 / Chapter 3.2.1 --- Performance according to cholesterol values in the UK population --- p.72 / Chapter 3.2.2 --- Performance according to treatment cut-offs in the UK population --- p.73 / Chapter 3.2.3 --- Performance according to cholesterol values in the Chinese population --- p.73 / Chapter 3.2.4 --- Performance according to the risk cut-offs in the Chinese population --- p.74 / Chapter 3.2.4 --- Performance using different risk equations --- p.76 / Chapter 3.3 --- Comparison with other existing screening models --- p.77 / Chapter 3.3.1 --- Performance of the 3 models within an age-restricted UK population --- p.79 / Chapter 3.3.2 --- Performance of the 3 models within an age-restricted Chinese population --- p.81 / Chapter 3.3.3 --- Performance of the 3 models in the entire UK population --- p.83 / Chapter 3.3.4 --- Performance of the 3 models in the entire Chinese population --- p.84 / Chapter 3.3.5 --- Costs of various screening options --- p.87 / Chapter 3.3.6 --- Number of CVD events avoidable of the screening programmes --- p.92 / Chapter 4 --- Discussion --- p.96 / Chapter 4.1.1 --- Performance at different hypothetical cholesterol values --- p.96 / Chapter 4.1.2 --- Performance at various treatment cut-off thresholds --- p.97 / Chapter 4.1.3 --- Performance with different risk equations --- p.98 / Chapter 4.1.4 --- Performance in different populations --- p.99 / Chapter 4.1.5 --- Performance with different survival functions --- p.99 / Chapter 4.2 --- Further modifications of the model --- p.100 / Chapter 4.2.1 --- A model without any cholesterol measurement --- p.100 / Chapter 4.2.2 --- Age restriction for selective models --- p.102 / Chapter 4.2.3 --- Our model with potential personalized treatment cut-off --- p.103 / Chapter 4.2.4 --- Three key things to ensure model performance in other population --- p.104 / Chapter 4.3 --- CVD events preventable --- p.105 / Chapter 4.3.1 --- Importance of age restriction --- p.105 / Chapter 4.3.2 --- Limitations of the NICE model --- p.106 / Chapter 4.4 --- Costs of different screening models --- p.107 / Chapter 4.4.1 --- Cost from different perspectives --- p.107 / Chapter 4.4.2 --- Cholesterol measurement cost and routine data collection --- p.108 / Chapter 4.4.3 --- Cost components --- p.109 / Chapter 4.4.4 --- Ways to reduce cholesterol measurement costs --- p.109 / Chapter 4.4.5 --- Costs and gain of the missing 2.5% high risk individuals --- p.109 / Chapter 4.5 --- Strengths and limitations of this study --- p.110 / Chapter 4.6 --- Recommendations --- p.113 / References --- p.114

Critical Access Hospitals (CAHs) – the predominant type of hospital operating in rural areas – play an integral role in the US healthcare system, providing care for over 7 million rural residents each year who might otherwise have no local access to urgent care or inpatient services. This dissertation examines three aspects of care delivery in CAHs – effectiveness, cost/efficiency, and access – each of which has separate implications for policy and practice. The first study addresses effectiveness and evaluates the performance of CAHs on specific patient safety indicators compared to small Prospective Payment System (PPS) hospitals. A total of 35,674 discharges from 136 non-federal general hospitals with fewer than 50 beds were included in the analyses: 14,296 from 100 CAHs and 21,378 from 36 PPS hospitals. Outcome measures included six bivariate indicators of adverse events of surgical care that were developed from Agency for Healthcare Research and Quality Patient Safety Indicators. Multiple logistic regression models were developed to examine the relationship between hospital adverse events and CAH status. The results indicated that compared to PPS hospitals, CAHs are less likely to have any observed (unadjusted) adverse event on all six indicators, four of which are statistically significant. After adjusting for patient mix and hospital characteristics, CAHs perform better on three of the six indicators. Accounting for the number of discharges eliminated the differences between CAHs and PPS hospitals in the likelihood of adverse events across all indicators except one. Tele-emergency (tele-ED) services can address several challenges facing emergency departments (EDs) in rural areas. The second study investigates access and characterizes the impact of a rural-ED-based telemedicine program on discharge disposition in terms of patient transfer, local hospital admission, and routine discharge. This study tests the hypothesis that telemedicine enhances access by allowing patients to receive care in the local community, and does so by looking at the probability of transfer and local admissions before and after telemedicine was implemented in CAHs. The results indicate that in the post-telemedicine period, patients were 38% less likely to be admitted to the local inpatient facility than to be routinely discharged [aOR=0.62, 95%CI=(0.57,0.67)] after adjusting for age, sex, race, time of visit, clinical diagnosis, CPT code, number of diagnoses, and admitting hospital. The third study addresses cost and efficiency by modeling the financial implications of using the same telemedicine program to avoid transfers and estimating the costs and benefits associated with tele-ED implementation in CAHs. Analysis is based on 9,048 tele-ED encounters generated by the Avera eEmergency program in 85 rural hospitals across seven states between October 2009 and February 2014. For each non-transfer patient, physicians indicated whether the transfer was avoided because of tele-ED activation. The cost-benefit analysis is conducted from the hospital, patient, and societal perspectives, and includes technology costs, local hospital revenues, and patient-associated savings. The results show that 1,175 avoided transfers could be attributed to tele-ED. From a rural hospital perspective, tele-ED costs around $1,739 to avoid a single transfer but saves approximately $5,563 in avoided transportation and indirect patient costs. From a societal perspective, tele-ED results in a net savings of $3,823 per avoided transfer while accounting for tele-ED technology costs, hospital revenues, and patient-associated savings. This study highlights various stakeholder perspectives on the financial impact of tele-ED in avoiding patient transfers in rural EDs. Telemedicine has the potential to reduce the number of transfers of ED patients and generate some revenue for rural hospitals despite associated technology costs, while incurring substantial patient savings.

La prise en charge contemporaine du cancer repose de plus en plus sur le concept de médecine dite personnalisée qui permet, après identification des caractéristiques propres de la tumeur, d'envisager une thérapeutique adaptée à chaque patient. La meilleure connaissance de la biologie des cancers et la mise en évidence de nouvelles cibles thérapeutiques ont ainsi abouti au développement des thérapies ciblées qui vont agir sur une cible cellulaire, généralement surexprimée au niveau d'une tumeur, leur conférant une plus grande spécificité d'action tumorale et un profil d'effets indésirables moins marqué par rapport à la thérapie cytotoxique conventionnelle. Malgré les données d'efficacité clinique, rapportées sur les stratégies thérapeutiques intégrant des thérapies ciblées, on ne dispose pas, malheureusement, des études pharmaco-économiques en cancérologie surtout que ces médicaments se caractérisent par leurs coûts très élevés (exemple: bevacizumab 1000 euros/400 mg ; cetuximab 964 euros/500 mg) et doivent donc être également appréhendés dans le cadre d'études dites en condition de vie réelle. L'objectif de ce projet de recherche est donc de proposer une étude pharmaco- économique sur l'utilisation des thérapies ciblées en cancérologie. Compte tenu du large champ d'investigation, deux affections tumorales distinctes seront considérées : le cancer colorectal métastatique et le glioblastome.Le cancer colorectal fera l'objet d'une étude conduite spécifiquement au Liban et le glioblastome d'une étude en France. L'originalité de cette thèse, conduite dans le cadre d'une coopération franco-libanaise, sera également d'évaluer les impacts médico-économiques de ces nouvelles stratégies selon des perspectives d'organismes payeurs très différentes, ce qui permettra d'appréhender les éventuelles problématiques d'accès aux soins / Although cancer incidence and prevalence are increasing at an alarming rate, progress in the treatment has been slow and treatment benefits are measured in weeks to months. Following the progress in the diagnostic tools and early detection biomarkers, a number of cancer types can be detected before pathological symptoms develops and this is of great significance because individual specific treatment regimens can be designed based on the presence and stage of cancer. In the past decade, there have been considerable improvements in the way that tumors are characterized and knowledge of cancer, at the molecular level has therefore increased greatly and has shift towards the use of targeted cancer therapies that display greater sensitivity and specificity for tumor cells by blocking the activity of the molecule in the host microenvironment that supports tumor growth or inhibiting the activity of protein tyrosine kinases or signaling pathways. Unfortunately, many pharmaco-economic studies are lacking today in the oncologic field. In addition, targeted therapies are very expensive (bevacizumab costs 100 euros/400mg and cetuximab 964 euros/500 mg) and should, therefore, be analyzed in real life conditions. That’s why the main objective of this research-project is to find a pharmaco-economic method on the use of the targeted therapies in oncology. Given the wide scope of investigations, 2 different tumor pathologies will be discussed: metastatic colorectal cancer and glioblastoma. The choice between these 2 cancer types takes place in the growing role of the targeted therapies in the effectiveness and survival of patients as well as their relative costs, especially that they have in common “bevacizumab” targeting the tumor vasculature

<p>With 7 000 new cases in Sweden each year, breast cancer represents 30 percent of all female malignancies and is therefore the most commonly diagnosed cancer among women. There are limitations as to what can be done to prevent the disease but with the use of mammography screening the chances of finding and treating the disease at an early stage are increasing. Unfortunately, mammography screening is associated with radiation, which is an established risk factor for developing breast cancer. However, the newest screening technologies come with a reduced dose which decreases the risk of developing breast cancer due to the radiation.</p><p> </p><p>The effects of this lower dose compared to that of traditional technologies have not yet been studied and the purpose of this paper is therefore to assess the cost-effectiveness of the use of this new technology, with a focus on the number of radiation-induced cancers. A cost-utility analysis was performed where three different mammography technologies (one analogue and two digital) were compared. The total costs and QALYs of breast cancer generated by the use of these three technologies were calculated with the use of a Markov decision-analytic model, where a cohort of hypothetical 40 year-old women was followed throughout life.</p><p> </p><p>The results of the analysis showed that with the new digital technology (the PC-DR), one in 14 100 screened women develops breast cancer due to radiation while with the traditional mammography systems (SFM and the CR) this number is one in 3 500 and 4 300 screened women, respectively. Consequently, the number of induced cancers is decreased with up to 75 percent with the use of the PC-DR. Assuming that only the radiation dose differs between the three units, the analysis resulted in an incremental effect of 0.000269 QALYs over a life-time for the PC-DR when compared to SFM(0.000210 QALYs compared to the CR). The PC-DR was also associated with a 33 SEK (26 SEK) lower cost. Thus, if the only difference can be found in radiation dose, the PC-DR is the dominating technology to use since it is both more effective and costs less. However, it is possible that the PC-DR is more expensive per screening occasion than the other technologies and if so, the PC-DR would no longer be less costly. The study found that the scope for the possibility of excessive pricing is very small and under these circumstances, the willingness to pay for a QALY has to be considered when deciding what technology to invest in.</p>

In cardiac surgery, sternal wound infection (SWI) continues to be one of the most serious postoperative complications. Coagulase-negative staphylococci (CoNS) have become the most common causative agents of SWI. Prophylaxis with intravenous beta-lactam antibiotics (cephalosporins or in Sweden most commonly isoxazolyl penicillins) is routinely practised. However, many CoNS species are resistant to beta-lactam antibiotics. Vancomycin is often the only effective antibiotic available for treatment of these infections, but its use for routine prophylaxis is strongly discouraged because of the risk of increasing the selection of resistant bacteria. The aim of this work was to develop and evaluate a new technique for antibiotic prophylaxis in cardiac surgery consisting of application of drug eluting collagen-gentamicin sponges in the sternal wound in addition to conventional intravenous antibiotics. The antibiotic concentrations in the wound and serum achieved by routine intravenous dicloxacillin prophylaxis and those after application of local collagen-gentamicin in the sternal wound were investigated. These studies showed dicloxacillin levels adequate for prevention of infections by methicillin-susceptible staphylococci, and extremely high gentamicin levels in the wound fluid, during the first 8-12 hours postoperatively with the local application. Two thousand cardiac surgery patients were then randomised to routine prophylaxis with intravenous isoxazolyl penicillin alone (control group) or to this prophylaxis combined with application of collagen-gentamicin (260 mg gentamicin) sponges within the sternotomy before wound closure. The primary end-point was any sternal wound infection within two months postoperatively. Evaluation was possible in 983 and 967 patients in the treatment and control groups, respectively. The incidence of any sternal wound infection was 4.3% in the treatment group and 9.0 % in the control group (relative risk = 0.47, (95% confidence interval 0.33 to 0.68); P&lt;0.001). The most common microbiological agents were CoNS, followed by Staphylococcus aureus. Local gentamicin reduced the incidence of SWIs caused by all major, clinically important microbiological agents except Propionibacterium acnes. Assignment to the control group, high body mass index, diabetes mellitus, younger age, single or double internal mammary artery, left ventricular ejection fraction less than 35% and longer operation time were independent risk factors for SWI in a multivariable risk factor analysis. In patients with additional sternal fixation wires (&gt; six wires) the collagen-gentamicin prophylaxis was associated with an approximately 70 % reduction in the incidence of SWI at all depths and the application of collagen sponges between sternal halves may require particular attention regarding the stability of fixation. A cost effectiveness analysis showed that the application of local collagen-gentamicin as prophylaxis was dominant, i.e. resulted in both lower costs and fewer wound infections. Routine use of the described prophylaxis in all adult cardiac surgery patients could be recommended.

The purpose of this thesis is to develop a model for assessing cost effectiveness of applying lean tools. The model consists of eight phases: it starts by understanding customers' requirements using Voice of Customer (VOC) and Quality Function Deployment (QFD) tools. In phase 2, the current state of plant is assessed using lean profile charts based on Balanced Scorecard (BSC) measures. In phase 3 and phase 4, identification of critical problem(s) and generating of improvement suggestion(s) are performed. Phase 5 provide evaluation of the cost effectiveness of implementing the suggested lean methods based on life cycle cost analysis (LCCA) and phase 6 prefers the right alternative based on multiple criteria decision making (MCDM). In phase 7 the selected alternative is supposed to be implemented and finally the user should monitor and control the process to make sure that the improvement is going as planned. The model was verified successfully using a case study methodology at one Swedish sawmill called Södra Timber in Ramkvilla, one part of Södra group. Results obtained from the study showed that the production and human resources perspectives are the most critical problem areas that need to be improved. They got the lowest scores in the lean profile, 63% and 68%, respectively. Using value stream mapping (VSM) it was found that the non value added (NVA) ratios for the core and side products are 87.4% and 90.4%, respectively. Using the model, three improvement alternatives were suggested and evaluated using LCCA and MCDM. Consequently, implementing 5S got the highest score, second came redesigning the facility layout. However, it was estimated that 4.7 % of NVA for the side product would be reduced by redesigning the facility layout. The recommendations were suggested for the company to improve their performance. The novelty of the thesis is based on the fact that it addresses two main issues related to lean manufacturing: firstly, suggesting lean techniques based on assessment of lean profile that is based on BSC and QFD, and secondly assessing the cost effectiveness of the suggested lean methods based on LCCA and MCDM. This thesis provides a generalized model that enables the decision-maker to know and measure, holistically, the company performance with respect to customer requirements. This will enable the company to analyze the critical problems, suggest solutions, evaluate them and make a cost effective decision. Thus, the company can improve its competitiveness.

To stay competitive, companies are forced to improve their products continuously. Field data is a source of information that shows the actual performance of products during operation, and that information can be used to clarify the items in need of improvements. This master thesis aims at identifying the set of field data that is required for dependability improvements and to develop a working procedure that enables increased utilization of the field data in order to make cost-effective design improvements. To achieve this, a 12-step model called the Design Improvement Cycle (DIC) was developed and tested in a single case study. The field data need was identified using a top-down method and was included as a part of the DIC. Testing of the model showed that it was practicable and each step could be carried through, even though the last steps only could be tested hypothetically during discussions with concerned personnel. The model implied a working procedure that should be aimed at, according to personnel with competence within the subject. As the DIC appeared to be very flexible it should be possible to use within several areas. It was discovered that field data was not a sufficient source of information to support design improvements but it could be used to indicate which items that should be focused on during further investigations. The quality of the field data had a big impact on the analysis possibilities and to point out which data quality issues that had to be amended to make the data more useful, the data need for dependability improvements could be used.

With 7 000 new cases in Sweden each year, breast cancer represents 30 percent of all female malignancies and is therefore the most commonly diagnosed cancer among women. There are limitations as to what can be done to prevent the disease but with the use of mammography screening the chances of finding and treating the disease at an early stage are increasing. Unfortunately, mammography screening is associated with radiation, which is an established risk factor for developing breast cancer. However, the newest screening technologies come with a reduced dose which decreases the risk of developing breast cancer due to the radiation.   The effects of this lower dose compared to that of traditional technologies have not yet been studied and the purpose of this paper is therefore to assess the cost-effectiveness of the use of this new technology, with a focus on the number of radiation-induced cancers. A cost-utility analysis was performed where three different mammography technologies (one analogue and two digital) were compared. The total costs and QALYs of breast cancer generated by the use of these three technologies were calculated with the use of a Markov decision-analytic model, where a cohort of hypothetical 40 year-old women was followed throughout life.   The results of the analysis showed that with the new digital technology (the PC-DR), one in 14 100 screened women develops breast cancer due to radiation while with the traditional mammography systems (SFM and the CR) this number is one in 3 500 and 4 300 screened women, respectively. Consequently, the number of induced cancers is decreased with up to 75 percent with the use of the PC-DR. Assuming that only the radiation dose differs between the three units, the analysis resulted in an incremental effect of 0.000269 QALYs over a life-time for the PC-DR when compared to SFM(0.000210 QALYs compared to the CR). The PC-DR was also associated with a 33 SEK (26 SEK) lower cost. Thus, if the only difference can be found in radiation dose, the PC-DR is the dominating technology to use since it is both more effective and costs less. However, it is possible that the PC-DR is more expensive per screening occasion than the other technologies and if so, the PC-DR would no longer be less costly. The study found that the scope for the possibility of excessive pricing is very small and under these circumstances, the willingness to pay for a QALY has to be considered when deciding what technology to invest in.