Barrett's Esophagus and Associated Adenocarcinoma : studies on pathogenesis, clinical staging and cost-utility of cancer treatment

Esophageal and gastroesophageal junction (GEJ) adenocarcinoma is rapidly increasing disease with a pathophysiology connected to oxidative stress. Exact pre-treatment clinical staging is essential for optimal care of this lethal malignancy. The cost-effectiviness of treatment is increasingly important. We measured oxidative metabolism in the distal and proximal esophagus by myeloperoxidase activity (MPA), glutathione content (GSH), and superoxide dismutase (SOD) in 20 patients operated on with Nissen fundoplication and 9 controls during a 4-year follow-up. Further, we assessed the oxidative damage of DNA by 8-hydroxydeoxyguanosine (8-OHdG) in esophageal samples of subjects (13 Barrett s metaplasia, 6 Barrett s esophagus with high-grade dysplasia, 18 adenocarcinoma of the distal esophagus/GEJ, and 14 normal controls). We estimated the accuracy (42 patients) and preoperative prognostic value (55 patients) of PET compared with computed tomography (CT) and endoscopic ultrasound (EUS) in patients with adenocarcinoma of the esophagus/GEJ. Finally, we clarified the specialty-related costs and the utility of either radical (30 patients) or palliative (23 patients) treatment of esophageal/GEJ carcinoma by the 15 D health-related quality-of-life (HRQoL) questionnaire and the survival rate. The cost-utility of radical treatment of esophageal/GEJ carcinoma was investigated using a decision tree analysis model comparing radical, palliative, and hypothetical new treatment. We found elevated oxidative stress ( measured by MPA) and decreased antioxidant defense (measured by GSH) after antireflux surgery. This indicates that antireflux surgery is not a perfect solution for oxidative stress of the esophageal mucosa. Elevated oxidative stress in turn may partly explain why adenocarcinoma of the distal esophagus is found even after successful fundoplication. In GERD patients, proximal esophageal mucosal anti-oxidative defense seems to be defective before and even years after successful antireflux surgery. In addition, antireflux surgery apparently does not change the level of oxidative stress in the proximal esophagus, suggesting that defective mucosal anti-oxidative capacity plays a role in development of oxidative damage to the esophageal mucosa in GERD. In the malignant transformation of Barrett s esophagus an important component appears to be oxidative stress. DNA damage may be mediated by 8-OHdG, which we found to be increased in Barrett s epithelium and in high-grade dysplasia as well as in adenocarcinoma of the esophagus/GEJ compared with controls. The entire esophagus of Barrett s patients suffers from increased oxidative stress ( measured by 8-OhdG). PET is a useful tool in the staging and prognostication of adenocarcinoma of the esophagus/GEJ detecting organ metastases better than CT, although its accuracy in staging of paratumoral and distant lymph nodes is limited. Radical surgery for esophageal/GEJ carcinoma provides the greatest benefit in terms of survival, and its cost-utility appears to be the best of currently available treatments.

Routine Measurement of Health-Related Quality of Life in Assessing Cost-Effectiveness in Secondary Health Care

Aims: The aims of this study were 1) to identify and describe health economic studies that have used quality-adjusted life years (QALYs) based on actual measurements of patients' health-related quality of life (HRQoL); 2) to test the feasibility of routine collection of health-related quality of life (HRQoL) data as an indicator of effectiveness of secondary health care; and 3) to establish and compare the cost-utility of three large-volume surgical procedures in a real-world setting in the Helsinki University Central Hospital, a large referral hospital providing secondary and tertiary health-care services for a population of approximately 1.4 million. Patients and methods: So as to identify studies that have used QALYs as an outcome measure, a systematic search of the literature was performed using the Medline, Embase, CINAHL, SCI and Cochrane Library electronic databases. Initial screening of the identified articles involved two reviewers independently reading the abstracts; the full-text articles were also evaluated independently by two reviewers, with a third reviewer used in cases where the two reviewers could not agree a consensus on which articles should be included. The feasibility of routinely evaluating the cost-effectiveness of secondary health care was tested by setting up a system for collecting HRQoL data on approximately 4 900 patients' HRQoL before and after operative treatments performed in the hospital. The HRQoL data used as an indicator of treatment effectiveness was combined with diagnostic and financial indicators routinely collected in the hospital. To compare the cost-effectiveness of three surgical interventions, 712 patients admitted for routine operative treatment completed the 15D HRQoL questionnaire before and also 3-12 months after the operation. QALYs were calculated using the obtained utility data and expected remaining life years of the patients. Direct hospital costs were obtained from the clinical patient administration database of the hospital and a cost-utility analysis was performed from the perspective of the provider of secondary health care services. Main results: The systematic review (Study I) showed that although QALYs gained are considered an important measure of the effectiveness of health care, the number of studies in which QALYs are based on actual measurements of patients' HRQoL is still fairly limited. Of the reviewed full-text articles, only 70 reported QALYs based on actual before after measurements using a valid HRQoL instrument. Collection of simple cost-effectiveness data in secondary health care is feasible and could easily be expanded and performed on a routine basis (Study II). It allows meaningful comparisons between various treatments and provides a means for allocating limited health care resources. The cost per QALY gained was 2 770 for cervical operations and 1 740 for lumbar operations. In cases where surgery was delayed the cost per QALY was doubled (Study III). The cost per QALY ranges between subgroups in cataract surgery (Study IV). The cost per QALY gained was 5 130 for patients having both eyes operated on and 8 210 for patients with only one eye operated on during the 6-month follow-up. In patients whose first eye had been operated on previous to the study period, the mean HRQoL deteriorated after surgery, thus precluding the establishment of the cost per QALY. In arthroplasty patients (Study V) the mean cost per QALY gained in a one-year period was 6 710 for primary hip replacement, 52 270 for revision hip replacement, and 14 000 for primary knee replacement. Conclusions: Although the importance of cost-utility analyses has during recent years been stressed, there are only a limited number of studies in which the evaluation is based on patients own assessment of the treatment effectiveness. Most of the cost-effectiveness and cost-utility analyses are based on modeling that employs expert opinion regarding the outcome of treatment, not on patient-derived assessments. Routine collection of effectiveness information from patients entering treatment in secondary health care turned out to be easy enough and did not, for instance, require additional personnel on the wards in which the study was executed. The mean patient response rate was more than 70 %, suggesting that patients were happy to participate and appreciated the fact that the hospital showed an interest in their well-being even after the actual treatment episode had ended. Spinal surgery leads to a statistically significant and clinically important improvement in HRQoL. The cost per QALY gained was reasonable, at less than half of that observed for instance for hip replacement surgery. However, prolonged waiting for an operation approximately doubled the cost per QALY gained from the surgical intervention. The mean utility gain following routine cataract surgery in a real world setting was relatively small and confined mostly to patients who had had both eyes operated on. The cost of cataract surgery per QALY gained was higher than previously reported and was associated with considerable degree of uncertainty. Hip and knee replacement both improve HRQoL. The cost per QALY gained from knee replacement is two-fold compared to hip replacement. Cost-utility results from the three studied specialties showed that there is great variation in the cost-utility of surgical interventions performed in a real-world setting even when only common, widely accepted interventions are considered. However, the cost per QALY of all the studied interventions, except for revision hip arthroplasty, was well below 50 000, this figure being sometimes cited in the literature as a threshold level for the cost-effectiveness of an intervention. Based on the present study it may be concluded that routine evaluation of the cost-utility of secondary health care is feasible and produces information essential for a rational and balanced allocation of scarce health care resources.

Kymijoen vaelluskalojen nousureittien avaamisen kustannusten ja hyötyjen arviointi

The objective of this thesis is to evaluate different means of increasing natural reproduction of migratory fish, especially salmon, in the river Kymijoki. The original stocks of migratory fish in Kymijoki were lost by the 1950s because of hydropower plants and worsened quality of water in the river. Nowadays the salmon stocks is based on hatchery-reared fish, even though there is significant potential of natural smolt production in the river. The main problem in the natural reproduction is that the migratory fish cannot ascend to the reproduction areas above the Korkeakoski and Koivukoski hydropower plants. In this thesis alternative projects which aim to open these ascencion routes and their costs and benefits are evaluated. The method used in the evaluation is social cost-benefit analysis. The alternative projects evaluated in this thesis consist of projects that aim to change the flow patterns between the eastern branches of Kymijoki and projects that involve building a fish ladder. Also different combinations of these projects are considered. The objective of this thesis is to find the project that is the most profitable to execute; this evaluation can be done in comparing the net present values of the projects. In addition to this, a sensitivity analysis will be made on the parameter values that are most uncertain. We compare the net present values of the projects with the net present values of hatchery-reared smolt releases, so we can evaluate, if the projects or the smolt releases are more socially profitable in the long term. The results of this thesis indicate that especially the projects that involve building a fish ladder next to the Korkeakoski hydropower plant are the most socially profitable. If this fish ladder would be built, the natural reproduction of salmon in the Kymijoki river could become so extensive, that hatchery-reared smolt releases could even be stopped. The results of the sensivity analysis indicate that the net present values of the projects depend especially on the initial smolt survival rate of wild salmon and the functioning of the potential fish ladder in Korkeakoski. Also the changes of other parameter values influence the results of the cost-benefit analysis, but not as significantly. When the net present values of the projects and the smolt releases are compared, the results depend on which period of time is selected to count the average catches of reared salmon. If the average of the last 5 years catches is used in counting the net benefits of smolt releases, all the alternative projects are more profitable than the releases. When the average of the last 10 years is used, only building of the fish ladder in Korkeakoski and all the project combinations are more profitable than the smolt releases.

Ilmastonmuutoksen ääri-ilmiöihin liittyvän riskienhallinnan kustannus–hyötyanalyysi osana julkista päätöksentekoa. IRTORISKI-hankkeen loppuraportti.

IRTORISKI-hankkeessa tutkittiin, miten kustannus–hyötyanalyysin käyttöä ilmastonmuutoksen sopeutumissuunnittelussa voitaisiin helpottaa niin, että sitä pystyttäisiin hyödyntämään kustannustehokkaasti sekä ilmastonmuutokseen liittyvien vaarojen priorisoinnissa että ennaltaehkäisevien toimenpiteiden vertailussa. Tutkimuksessa käytettiin esimerkkitapauksina jokitulvaa ja rankkasateiden aiheuttamaa tulvaa kaupunkiolosuhteissa. Tapahtumapuuanalyysia laajennettiin siten, että siitä käyvät ilmi sekä suorat vahingot että lopulliset makrotaloudelliset vaikutukset. Arviot suorista taloudellisista vahingoista perustuivat aikaisempiin tutkimuksiin, kun taas makrotaloudellisia vaikutuksia simuloitiin yleisen tasapainon mallin avulla. Tapaustutkimusten valinnasta, tapahtumapuun käytöstä, sen laajennusosasta sekä lasketuista makrotaloudellisista vaikutuksista keskusteltiin sidosryhmien edustajien kanssa kolmessa asiantuntijaistunnossa.

Evaluation of the profitability of fast-growing tropical trees.

The profitability of fast-growing trees was investigated in the northeastern and eastern provinces of Thailand. The financial, economic, and tentative environmental-economic profitability was determined separately for three fast-growing plantation tree species and for three categories of plantation managers: the private industry, the state (the Royal Forest Department) and the farmers. Fast-growing tree crops were also compared with teak (Tectona grandis), a traditional medium or long rotation species, and Para rubber (Hevea brasiliensis) which presently is the most common cultivated tree in Thailand. The optimal rotation for Eucalyptus camaldulensis pulpwood production was eight years. This was the most profitable species in pulpwood production. In sawlog production Acacia mangium and Melia azedarach showed a better financial profitability. Para rubber was more profitable and teak less profitable than the three fast-growing species. The economic profitability was higher than the financial one, and the tentative environmental-economic profitability was slightly higher than the economic profitability. The profitability of tree growing is sensitive to plantation yields and labour cost changes and especially to wood prices. Management options which aim at pulpwood production are more sensitive to input or output changes than those options which include sawlog production. There is an urgent need to improve the growth and yield data and to study the environmental impacts of tree plantations for all species and plantation types.

Costs and Benefits of a Shared Digital Long-Term Preservation System

This paper describes the cost-benefit analysis of digital long-term preservation (LTP) that was carried out in the context of the Finnish National Digital Library Project (NDL) in 2010. The analysis was based on the assumption that as many as 200 archives, libraries, and museums will share an LTP system. The term ‘system’ shall be understood as encompassing not only information technology, but also human resources, organizational structures, policies and funding mechanisms. The cost analysis shows that an LTP system will incur, over the first 12 years, cumulative costs of €42 million, i.e. an average of €3.5 million per annum. Human resources and investments in information technology are the major cost factors. After the initial stages, the analysis predicts annual costs of circa €4 million. The analysis compared scenarios with and without a shared LTP system. The results indicate that a shared system will have remarkable benefits. At the development and implementation stages, a shared system shows an advantage of €30 million against the alternative scenario consisting of five independent LTP solutions. During the later stages, the advantage is estimated at €10 million per annum. The cumulative cost benefit over the first 12 years would amount to circa €100 million.