Vitamin B12 Deficiency in the aged: Laboratory Diagnosis, Prevalence and Clinical Profile

B₁₂-vitamiinin puute iäkkäillä: laboratoriodiagnostiikka, yleisyys ja yhteys sairastavuuteen Tausta: B12-vitamiinin puute on yleistä iäkkäillä ja se tulisi todeta riittävän varhaisessa vaiheessa palautumattomien vaurioiden estämiseksi. On epäselvää pitäisikö diagnostiikka kohdistaa tiettyihin riskiryhmiin vai mahdollisesti seuloa valikoimatonta vanhusväestöä. Myöskään yksimielisyyttä laboratoriotutkimusten valinnasta ei ole. Tavoitteet: Tutkimuksen tarkoituksena oli evaluoida uutta HoloTC RIA menetelmää ja tuottaa viitearvot sille, selvittää B12-vitamiinin puutteen yleisyys, yhteys sairastavuuteen ja mahdolliset riskitekijät suomalaisessa vanhusväestössä, arvioida munuaisfunktion vaikusta B12-vitamiinin puutteen laboratoriotutkimuksiin ja näiden perusteella ehdottaa suomalaiseen terveydenhuoltoon sopivaa laboratoriotutkimusstrategiaa. Aineisto ja menetelmät: Liedon iäkkäät -tutkimuksen vanhusaineisto on edustava otos yhden kunnan yli 65-vuotiaasta väestöstä, yhteensä 1260 henkilöä. Tutkittavat kävivät lääkärintarkastuksessa, ja heistä on käytettävissä runsaasti laboratoriotutkimuksia sekä tiedot sairauksista, ruokavaliosta, lääkkeiden ja vitamiinivalmisteiden käytöstä, dementiaseula ja depressiokysely. Viitearvoaineistoa varten kerättiin näytteet 84 vapaaehtoisesta terveestä aikuisesta ja menetelmäevaluaatiota varten 107 sairaalapotilaasta. Tulokset: HoloTC RIA menetelmän toistettavuus oli hyvä manuaalimenetelmäksi. 95%:n viiteväli holotranskobalamiinille oli 37-171 pmol/l. Kaikilla tutkittavilla, joilla oli muilla laboratoriotutkimuksilla osoitettu todennäköinen B12-vitamiinin puute, myös holotranskobalamiini oli viitealueen alarajaa pienempi. Suurentuneella kystatiini C-pitoisuudella osoitettu munuaisten vajaatoiminta korreloi voimakkaasti homokysteiinin (rs=0.53, p<0.001) ja metyylimalonihapon (rs=0.27, p<0.001) pitoisuuksiin, mutta ei kokonais-B12-vitamiinin (rs=- 0.04, p=0.227) tai holotranskobamiinin (rs=-0.01, p=0.817) pitoisuuksiin. Suomalaisessa vanhusväestössä B12-vitamiinin puutteen prevalenssi oli 12%. Kokonais- B12-vitamiinin pitoisuus oli matala (<150 pmol/l) 6%:lla. Miessukupuoli (OR 1.9, 95% CI 1.2-2.9), ikä ≥75 (OR 2.2, 95% CI 1.4-3.4) ja maitotuotteiden välttäminen (OR 2.3, 95% CI 1.2-4.4) lisäsivät B12-vitamiinin puutteen riskiä, mutta anemia (OR 1.3, 95% CI 0.7-2.3) tai makrosytoosi (OR 1.2, 95% CI 0.6-2.7) eivät. Päätelmät: Diagnosoimaton B12-vitamiinin puute on yleistä iäkkäillä, mutta kliinisesti merkityksellistä spesifistä riskiryhmää ei löydy. Koska anemian ja makrosytoosin puuttuminen ei poissulje B12-vitamiinin puutetta ja munuaisten vajaatoiminta heikentää metabolisten merkkiaineiden käyttökelpoisuutta, kokonais-B12-vitamiinia suositellaan ensisijaiseksi laboratoriotutkimukseksi epäiltäessä B12-vitamiinin puutetta ja tarvittaessa varmentavina tutkimuksina käytetään homokysteiiniä ja holotranskobalamiinia.

Delivery of European Cross-Border Health Care and the Relevance and Effects of EU Regulations and Judicial Processes with Reference to Delivery of Drugs and Blood Donor Information Material.

Valtion rajat ylittävät terveyspalvelut Euroopan unionissa sekä Euroopan unionin säädösten merkitys ja vaikutus erityisesti lääkejakeluun ja verenluovuttajille jaettavaan tiedotusaineistoon Valtion rajat ylittävä terveydenhuolto on suuren kiinnostuksen kohteena Euroopan unionissa. Resurssien hyödyntäminen parhaalla mahdollisella tavalla ja tiedon keskittäminen ovat tarpeen terveydenhuollon kustannusten alati noustessa. Terveydenhuoltopalvelut kuuluvat Euroopan sisämarkkinoiden vapaan liikkuvuuden piiriin. Euroopan unionilla ei ole kuitenkaan toimivaltaa säädellä terveydenhuoltojärjestelmiä, vaan sen mahdollisuudet ovat enimmäkseen kansanterveyden edistämisessä ja suojelussa, myös muilla toimialueilla kuin terveydenhuollossa. Tutkimuksen tavoitteena oli tutkia Euroopan unionin säädösten vaikutusta terveydenhuoltosektoriin, erityisesti valtion rajat ylittäviin terveydenhuoltopalveluihin. Erityiskohteena olivat lääkemääräyksen toimittaminen toisen Euroopan unionin jäsenmaan apteekista, resepti-lääkkeiden maahantuonti omaan henkilökohtaiseen käyttöön, sähköisen lääkemääräyksen käyttö kansallisesti ja mahdollisuudet sen käyttöön eri jäsenmaiden välillä, online-apteekkien soveltuvuus Euroopan unionin sisämarkkinoille sekä verenluovuttajille jaettavan tiedotusaineiston yhtenäistämistarve Euroopan unionin alueella. Tutkimuksen osa-alueiden aineisto koottiin vuosina 1999–2003, jolloin Euroopan unioniin kuului 15 jäsenmaata. Apteekit toimittivat useimmiten myös ei-kansalliset, toisessa Euroopan unionin jäsenmaassa annetut lääkemääräykset. Kaikki jäsenmaat rajoittivat lääkemääräyksen vaativien lääkkeiden maahantuontia. Rajoituksia oli maahantuontimäärissä ja -tavoissa. Lisäksi sairasvakuutuskorvausten saaminen ulkomailla lunastetuista reseptilääkkeistä oli hankalaa. Sähköiset lääkemääräykset olivat käytössä vain kahdessa maassa, mutta useissa maissa suunniteltiin niiden kokeilua. Standardit ja käyttöjärjestelmät olivat erilaisia eri maissa. Euroopan unionin alueelle on perustettu online-apteekkeja, joiden toiminta on kuitenkin vaatimatonta. Verenluovuttajille annettava tiedotusaineisto ei missään maassa täyttänyt veridirektiivin vaatimuksia. Tutkimuksen tulokset osoittivat kansallisten käytäntöjen eroavaisuuksien rajoittavan valtion rajat ylittäviä terveydenhuoltopalveluita. Vaikka Euroopan unionin tavoitteena ei ole yhtenäistää terveydenhuoltojärjestelmiä, on tarpeen arvioida uudelleen unionin ja jäsenmaiden välistä työnjakoa. Kansalliset terveydenhuoltojärjestelmät eivät ole erillään Euroopan sisämarkkinoista, jotka merkittävästi vaikuttavat terveydenhuoltoon.

Customer Driven Service Development – Technology-based Care and Services for the Elderly

The objective of this master’s thesis was to examine technology-based smart home devices and services. Topic was approached through basic theories, transaction cost theory and resource-based view in order to build basis for this thesis. Conceptual framework was discussed by means of networks, value networks and service systems which provide a useful framework for service development. The needs of the elderly living at home were discussed in order to find out which technology-based services could be used to satisfy the needs. Segmentation and need data collected previously during proactive home visits was exploited and additionally a survey targeted to experts and professionals of social and health care sector was done to verify the needs. Finally, the results of the survey were analyzed using quality function deployment method to figure out the most important and suitable service offerings for the elderly. As a conclusion of analysis, social media and monitoring services are the most useful technology-based services. However, traditional home services will still maintain their necessity too.

Libyan breast cancer: Health services and biology. Diagnosis delay and prognostic value of DNA pploidy, S-phase fraction, and Ki-67 and Bcl-2 immunohistochemistry

The aim of this study was to investigate the diagnosis delay and its impact on the stage of disease. The study also evaluated a nuclear DNA content, immunohistochemical expression of Ki-67 and bcl-2, and the correlation of these biological features with the clinicopathological features and patient outcome. 200 Libyan women, diagnosed during 2008–2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. Also retrospective preclinical and clinical data were collected from medical records on a form (questionnaire) in association with the interview. Tumor material of the patients was collected and nuclear DNA content analysed using DNA image cytometry. The expression of Ki-67 and bcl-2 were assessed using immunohistochemistry (IHC). The studies described in this thesis show that the median of diagnosis time for women with breast cancer was 7.5 months and 56% of patients were diagnosed within a period longer than 6 months. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was also associated with initial breast symptom(s) that did not include a lump, old age, illiteracy, and history of benign fibrocystic disease. The patients who showed diagnosis delay had bigger tumour size (p<0.0001), positive lymph nodes (p<0.0001), and high incidence of late clinical stages (p<0.0001). Biologically, 82.7% of tumors were aneuploid and 17.3% were diploid. The median SPF of tumors was 11% while the median positivity of Ki-67 was 27.5%. High Ki-67 expression was found in 76% of patients, and high SPF values in 56% of patients. Positive bcl-2 expression was found in 62.4% of tumors. 72.2% of the bcl-2 positive samples were ER-positive. Patients who had tumor with DNA aneuploidy, high proliferative activity and negative bcl-2 expression were associated with a high grade of malignancy and short survival. The SPF value is useful cell proliferation marker in assessing prognosis, and the decision cut point of 11% for SPF in the Libyan material was clearly significant (p<0.0001). Bcl-2 is a powerful prognosticator and an independent predictor of breast cancer outcome in the Libyan material (p<0.0001). Libyan breast cancer was investigated in these studies from two different aspects: health services and biology. The results show that diagnosis delay is a very serious problem in Libya and is associated with complex interactions between many factors leading to advanced stages, and potentially to high mortality. Cytometric DNA variables, proliferative markers (Ki-67 and SPF), and oncoprotein bcl-2 negativity reflect the aggressive behavior of Libyan breast cancer and could be used with traditional factors to predict the outcome of individual patients, and to select appropriate therapy.

Managing regulatory risks when outsourcing network-related services in the electricity distribution sector

Deregulation of the electricity sector liberated the electricity sale and production for competitive forces while in the network business, electricity transmission and distribution, natural monopoly positions were recognised. Deregulation was accompanied by efficiencyoriented thinking on the whole electricity supply industry. For electricity distribution this meant a transition from a public service towards profit-driven business guided by economic regulation. Regulation is the primary means to enforce societal and other goals in the regulated monopoly sector. The design of economic regulation is concerned with two main attributes; end-customer price and quality of electricity distribution services. Regulation limits the costs of the regulated company but also defines the desired quality of monopoly services. The characteristics of the regulatory framework and the incentives it provides are therefore decisive for the electricity distribution sector. Regulation is not a static factor; changes in the regulatory practices cause discontinuity points, which in turn generate risks. A variety of social and environmental concerns together with technological advancements have emphasised the relevance of quality regulation, which is expected to lead to the large-scale replacement of overhead lines with underground cables. The electricity network construction activity is therefore currently witnessing revolutionary changes in its competitive landscape. In a business characterised by high statutory involvement and a high level of sunk costs, recognising and understanding the regulatory risks becomes a key success factor. As a response, electricity distribution companies have turned into outsourcing to attain efficiency and quality goals. This doctoral thesis addresses the impacts of regulatory risks on electricity network construction, which is a commonly outsourced activity in the electricity distribution network sector. The chosen research approach is characterised as an action analytical research on account of the fact that regulatory risks are greatly dependent on the individual nature of the regulatory regime applied in the electricity distribution sector. The main contribution of this doctoral thesis is to develop a concept for recognising and managing the business risks stemming from economic regulation. The degree of outsourcing in the sector is expected to increase in years to come. The results of the research provide new knowledge to manage the regulatory risks when outsourcing services.

The value of digitalization of services in the new service development

The purpose of this thesis is to study factors that have an impact on the company’s capabilities to identify and analyze the value of digitalization of services during the early stages of service development process and evaluate them from the perspective of a case company. The research problem was defined: “How digitalization of services affects delivering the services of the future?” The research method of this thesis was based on the qualitative case study which aimed to study both company’s and customer’s set of values. The study included a literature review and a development study. The empirical research part consisted of analyzing three existing services, specifying a new digital service concept and its feasibility analysis as part of a business requirement phase. To understand the set of values, 10 stakeholder interviews were conducted and earlier customer surveys were utilized, and additionally, a number of meetings were conducted with the case company representatives to develop service concept, and evaluate the findings. The impact of the early stages of service development process discovered to reflect directly in the capabilities of the case company to identify and create customer value were related to the themes presented in the literature review. In order to specify the value achieved from the digitalization the following areas of strategic background elements were deepened during the study: Innovations, customer understanding and business service. Based on the findings, the study aims to enhance the case company’s capability to identify and evaluate the impact of the digitalization in delivering services of the future. Recognizing the value of digital service before the beginning of the development project is important to the businesses of both customer and provider. By exploring the various levels of digitalization one can get the overall picture of the value gained from utilizing digital opportunities. From the development perspective, the process of reviewing and discovering the most promising opportunities and solutions is the key step in order to deliver superior services. Ultimately, a company should understand the value outcome determination of the individual services as well as their digital counterparts.

Productivity and Services – Safety Telephone Services for the Elderly

Previous research on productivity is often associated with manufacturing or uses manufacturing definitions of productivity. Marketing research on services has not been satisfied with the manufacturing definitions. No universal definition for service productivity exists. The lack of a universal definition highlights the complexity entailed in the concept of productivity. The objective of this study was to investigate service productivity in situations, where traditional ways are in some cases even not possible or are not enough. In one definition of the productivity of service organisations there is the efficiency of the organisation on the input side and on the output side the customers’ perceived quality or value-in-use. To learn about value-in-use, many methods have been developed. A common practice is to make customer opinion surveys in the form of customer questionnaires and interviews. However, customers cannot always be asked directly, for example, because of impaired cognitive abilities. Such cases include the elderly and children. Furthermore, customer opinion surveys are time consuming. In addition, customers do not always know what kind of services they would benefit from. For the empirical part of the study, a business area was identified where traditional ways of measuring value-in-use are difficult or in some cases even not possible. This business area is safety telephone services. These services are most often used by the elderly. The way to define value-in-use here was to assess how well the services offered met customer expectations. Comparing the services customers asked for and the services provided to them indicated whether customer expectations were met. This study showed that customers had their ideas concerning the contents of the services but many times the services provided did not meet these expectations. Organisational efficiency aspirations can decrease customers’ value-in-use. This study found a solution, in which increasing organisational efficiency would go hand-in-hand with increasing customers’ value-in-use; the result being that the organisations’ needs and the service users’ expectations were in line. Value creation for customers produced organisational efficiency and thus increased productivity. In this study, customer expectations were observed by means of wellness technology. With the help of modern technology, customer expectations can be followed quickly and easily and customers can co-create with the organisation. This type of an approach could be useful even in the development of other services for other ages and in different contexts. If a service organisation decreases the number of personnel and, at the same time, tries to offer services to the same or a larger clientele, customers easily notice the change, which is often negative. To avoid harmful decrease in value-in-use, limitations to the aspiration of efficiency should be implemented – one of such is that the organisation is required to meet certain quality standards defined by experts. The aim is to secure that, as a result of efficiency aspirations in the organisation, the quality of the service offerings does not diminish below mutually agreed standards. Traditionally, when productivity in services has been estimated, organisational efficiency has not been combined with both customer expectations and an expert assessment of quality. This study contributes with novel thinking entitled ‘Relationship Management of the Elderly’. This study handles productivity, expert defined quality and value-in-use in an organisational context, which is practically untouched in previous research studies.